www.psychiatry-malaysia.org
www.neuro.org.myGUIDELINE DEVELOPMENT
The development group for these guidelines comprised of family medicine
specialists, geriatricians, psychiatrists, geriatric psychiatrists, a neurologist, a
psychologist, a public health specialist, an occupational therapist, a scientificofficer and pharmacists from the Ministry of Health and the Ministry of Higher
Education, Malaysia. During the process of development of these guidelines,
there was active involvement of a review committee from both the public andprivate sector, consisting of geriatricians, psychiatrists, occupational therapist,
neurologists and a representative from the caregivers group.
This document is the 2nd Edition of Clinical Practice Guideline (CPG) on theManagement of Dementia updating the previous CPG on Management of
Dementia (2003). Since the publication of the first guidelines, there have been
many advances in the field of dementia and mild cognitive impairment. Thereis a movement towards very early detection of dementia with the developmentof genetic, neuroimaging and biomarkers. Acetylcholinesterase inhibitors (AChEI)
have been around for the past twenty years for the treatment of Alzheimer disease
and related dementias. Currently there has been another drug developed to treat
severe dementia. There are also many more drugs undergoing Phase II and III
trials that are targetting beyond the neurotransmitters. Drugs and other preventive
measures, such as exercise and mental stimulation, have been investigatedto determine the extent of risk that these factors have in the development ofdementia.
This CPG was adapted from DEMENTIA, A nice –SCIE Guideline on Supporting
People with Dementia and their Cares in Health and Social Care, the British
Psychological Society & Royal College of Psychiatrists, 2006 and the Scottish
Intercollegiate Guidelines Network, Management of Patients with Dementia,
February 2006. These CPGs were evaluated using the Appraisal of Guidelines
for Research and Evaluation (AGREE) tool prior to adaptation. Further evidence
was then retrieved from 2006 onwards. For the purposes of updating theseguidelines, June 2009 should be considered the starting point for searching for
new evidence.
iLiterature search was carried out at the following electronic databases, PUBMED/MEDLINE, PsycINFO, Cochrane Database of Systemic Reviews (CDSR),International Health Technology Assessment Websites, Journal full text via the
OVID search engine, Database of Abstracts of Reviews of Effectiveness; CochraneControlled Trials Registered, Clinical Trial and Registry, EBSCO search engine. A
snowball method was used to manually check the references of the included
studies to identify any relevant studies that had not yet been included. Refer toAppendix 1 for the search terms used to retrieve articles.
Reference was also made to other guidelines such as the Ministry of HealthSingapore - Clinical Practice Guideline, Dementia, 2006 and the Royal
Australian College of General Practitioners, Care of Patients with Dementia in
General Practice, September 2003.
The clinical questions were divided into four subgroups and members of thedevelopment group were assigned individual clinical question within thesesubgroups. The group members met a total of 25 times throughout thedevelopment of the guidelines. All literature retrieved were appraised by at least
two members, presented in the form of evidence tables and discussed duringgroup meetings. All the statements and recommendations formulated wereagreed upon by both the development group and review committee. Where theevidence was insufficient, the recommendations were derived by consensus of
the development group and review committee. This CPG is based largely on thefindings of systematic reviews and meta-analyses in the literature, taking into
consideration local practices.
These articles were graded using U.S. Preventive Services Task Force while
the grading of recommendation in this guideline was modified from grades ofrecommendation of the Scottish Intercollegiate Guidelines Network (SIGN). Refer
to inside back cover for Levels of Evidence and Grade of Recommendations.
The draft guideline was posted on the Ministry of Health Malaysia and Family Medicine
Specialist websites for comment and feedback. These guidelines had also beenpresented to the Technical Advisory Committee for Clinical Practice Guidelines, andthe Health Technology Assessment and Clinical Practice Guidelines Council, Ministryof Health Malaysia for review and approval.
ii

OBJECTIVE
GENERAL OBJECTIVES
The aim of these guidelines is to assist clinicians in making evidence based
decisions on the management of people with dementia and their caregivers.

SPECIFIC OBJECTIVES
R To describe the syndrome of dementia and its common subtypes aswell as mild cognitive impairment
R To discuss risk factors and preventive strategies in the development ofdementia
R To review the assessment and diagnostic tools in dementia
R To provide evidence based guidance on the management for people

with dementia and mild cognitive impairment
R To address the ethical issues and end-of-life issues in dementia
R To understand the impact of dementia on the individual and caregiver

CLINICAL QUESTIONS
Refer to Appendix 2 for details

TARGET POPULATIONa.

Inclusion Criteria (Target Group)
Adults with dementia and mild cognitive impairmentb.

Exclusion criteria
People with learning disabilities who develop dementia anddementia secondary to medical conditions e.g. normal pressurehydrocephalus, AIDS, dementia complex, etc.

iii

TARGET USERS
These guidelines are applicable to healthcare professionals who are involved in
the management of dementia:R Primary Care Physicians
R Psychiatrist/Geriatric Psychiatrist/Neuropsychiatrist
R Physicians/Geriatricians/Neurologists
R Nurses
R Social Workers
R Physiotherapists/Occupational Therapists
R Pharmacists
R Psychologists
R And all others involved in the management of patients with dementia

HEALTH CARE SETTINGS
Outpatient, inpatient and community setting

PROPOSED CLINICAL AUDIT INDICATORS FOR QUALITY MANAGEMENT
Indicator
Percentage of people with a possible diagnosis of dementia from primary clinic referred
to memory clinics/specialist clinic =Total number of those suspected dementia whoare referred from primary care to memory clinic

x 100%

Total number of referrals for suspected
dementia in the memory clinic
Percentage of patients with BPSD prescribed atypical antipsychotics =Number of patients with BPSD prescribedatypical antipsychotics appropriately
Total number of BPSD casesiv

x 100%GUIDELINE DEVELOPMENT GROUP
Chairperson
Dr. Suraya Yusoff
Head of Department and Senior Consultant Geriatric Psychiatrist
Hospital Sultan Ismail
Johor

Members (alphabetical order)
Dr. Bharathi Vengadasalam
Geriatric Psychiatrist and Senior Lecturer
Faculty of Medicine and Health Sciences
Universiti Putra Malaysia, Serdang, Selangor

A/Prof Normah Che Din
Clinical Psychologist and Lecturer
Faculty of Allied Health Sciences
Universiti Kebangsaan Malaysia
Kuala Lumpur

Ms Hor Yee Yee
Pharmacist
Hospital Sultan Ismail
Johor

Dr. Norzarina Md Zabidi
Clinical Psychiatrist
Hospital Melaka
MelakaDr. Ismail Drahman
Head of Department and Senior Consultant
Geriatric Psychiatrist
Hospital Umum Sarawak. Sarawak

Dr. Shanti Viswanathan
Neurologist
Neurology Department
Hospital Kuala Lumpur, Kuala Lumpur

Dr. Khairuddin A. Wahab
Consultant Psychiatrist
Hospital Permai, Johor Bharu
Johor

Dr Sheamini Sivasampu
Public Health Physician
Health Technology Assessment Section
Medical Development Division, MOH

Dr. Joseph Ngeh
Consultant Geriatrician
Hospital Umum Sarawak, Sarawak

Dr. Sukumar Rajaretnam
Family Medicine Specialist
Poliklinik Komuniti Tanglin, Kuala Lumpur

Dr. Lee Fatt Soon
Senior Consultant Geriatrician
Hospital Kuala Lumpur
Kuala Lumpur

Mr.Tan Chee Chin
Pharmacist
Hospital Sultanah Aminah, Johor Bharu
Johor

Ms. Mariammah Krishnasamy
Scientific Officer ( Microbiology)
Health Technology Assessment Section
Medical Development Division, MOH

Mr.Thillainathan Krishnan
Occupational Therapist
Hospital Selayang
SelangorDr. Mohd Daud Che Yusof
Family Medicine Specialist
Klinik Kesihatan Sungai Mati,Muar, Johor

Dr. Yau Weng Keong
Senior Consultant Geriatrician
Hospital Kuala Lumpur, Kuala Lumpur

Dr. Norhashim Ahmad
Consultant Neuropsychiatrist
Hospital Sultanah Aminah, Johor Bharuv

REVIEW COMMITTEE
The draft guideline was reviewed by a panel of independent expert referees, whowere asked to comment primarily on the comprehensiveness and accuracy ofinterpretation of the evidence supporting the recommendations in the guidelines.

Chairperson
Professor Dr. Phillip Poi Jun Hua
Senior Consultant Geriatrician
Universiti Malaya Medical Centre
Kuala Lumpur

Members (alphabetical order)
Dr. Chin Ai-Vyrn
Consultant Geriatrician and Senior Lecturer
Universiti Malaya Medical Centre
Kuala Lumpur

Datin Dr. Rugayah Bakri
Deputy Director
Health Technology Assessment Section
Medical Development Division, MOH

Dr. Esther Ebenezer
Consultant Geriatric Psychiatrist and Lecturer
Universiti KL Royal Medical College Ipoh
Perak

Dato’ Dr. Suarn SinghHead of Services for Psychiatry and
Senior Consultant Psychiatrist
Hospital Bahagia Ulu Kinta, Perak

Prof Dr. Goh Khean Jin
Senior Consultant Neurologist
Universiti Malaya Medical Centre
Kuala Lumpur

Puan Tan Foo Lan
Head of Department
Department of Occupational Therapy
Hospital Kuala Lumpur

Prof Dr. Raymond Azman Ali
Deputy Dean and Senior Consultant Neurologist
Universiti Kebangsaan Malaysia Medical Centre
Kuala Lumpur

Dr. Yen Teck Hoe
President
Malaysian Psychiatrist Association
Hospital Tung Shin
Kuala Lumpur

Associate Prof (Clinical) Dr. Rosdinom Razali
Consultant Psychiatrist and Geriatric Psychiatrist
Universiti Kebangsaan Malaysia Medical Centre
Kuala Lumpur

Datuk Dr. Yim Khai Kee
Chairman of the Executive Committee
Alzheimer Disease Foundation Malaysia
Kuala Lumpurvi

EXTERNAL REVIEWERS
The draft guideline was also reviewed by a panel of external reviewers
Professor Helen Chiu
Professor & Head of the Department of Psychiatry
Chinese University of Hong Kong
Hong Kong

Professor Rachelle Doody
Effie Marie Cain Chair in Alzheimers Disease
Research Dept of Neurology and Alzheimers
Disease and Memory Disorder Centre Baylor
College of Medicine, Houston, Texas

Professor Dr Khoo Ee Ming
Department of Primary Care Medicine
University of Malaya
Kuala Lumpur

Datuk Dr. Raihanah Abd Khalid
Consultant Neurologist
Assunta Hospital
Selangor

Professor Leon Flicker
Professor & Geriatric Medicine Director
Western Australia Centre for Health & Ageing
University of Western Australia
Royal Perth Hospital

Dr. P. Srinivas
Consultant Geriatrician/Chest Physician
Gleneagles Medical Centre Penang
PenangDr. Mohd Faudzi Abdullah
Family Medicine Specialist
Klinik Kesihatan Padang Serai
Kulim, Kedah

Dr. Theva Raj Ponnudurai
Head of Services for Rehabilitation Medicine &Senior Consultant Rehabilitation Specialist
Hospital Tuanku Jaafar, Seremban, Negeri Sembilan

Dr. Mohmad bin Salleh
Public Health Specialist
Family Health Development Division
Ministry of HealthDr. Yoong Kar Yaw
Head of Department andSenior Consultant Physician
Hospital Sultan Ismail
Johor

Madam Pushpamani Navaratinarajah
Nursing Tutor
Nursing School, Seremban ,Negeri Sembilanvii

ALGORITHM ON SCREENING OF DEMENTIA IN PRIMARY CARE
Presence of symptoms suggestive of dementia (including subjective
memory complaint, changes in ADL and/or caregivers concerns)

Refer to specialist
services/memory clinics

Do the findings meetcriteria for dementia?

Is the patient
cognitively impaired
but not demented- HScreening tests : FBC, Renal profile,Ca, LFT, Folate, B12,TFT, UFEME, RBS/FBS, Lipid profile.
- Specific test guided by clinical presentation : VDRL, HIV, etc.

viii

ALGORITHM FOR DIAGNOSIS OF DEMENTIA AT SECONDARY / TERTIARY LEVELALGORITHM FOR DIAGNOSIS OF DEMENTIA AT SECONDARY/TERTIARY LEVEL
Presence of symptoms suggestive of dementia
or referral from primary / secondary care level
Perform clinical assessment:• history from patients and caregivers• examinationr physical including cardiovascular and neurological systems
r cognition (e.g. MMSE, CDT)r mental state (e.g. GDS/CSDD, BPRS/NPI)r function (e.g. IADL/ ADL)r others (e.g. Hachinski)

Is patient cognitively
impaired ?

NO

Reassess after 6 months

Depression/Delirium

YES• Blood Investigation (FBC, ESR, Renal profile, Ca, LFT,
Glucose (RBS/FBS), Lipid profile, TFT, B12, Folate, Urine
FEME, Urine C&S)
• ECG
• If indicated, specific tests (e.g. VDRL, HIV, etc.)

DEMENTIA or MCI ?

NO

YES• Perform MRI / CT
• EEG if indicatedNO

DEMENTIA

MCI

YES

Determine type of dementia

Alzheimer
disease

Vascular
Dementia

Dementia of Lewy Frontotemporal
Body/Parkinson
dementia
Disease Dementiaix

Other types of dementia• “Reversible dementia” e.g. thyroid
dysfunction, vitamin deficiency• other dementias e.g. HIV

Maintenance ofcognitive function

Activities topromote independence

Maintenance of functions(intervention for patient and caregivers)

Multidisciplinary team assessment

Psychosocial Intervention (as tailored to individual’s needs)

Alzheimer’s disease

Vascular dementia...........................................................

Treat vascular risk factors...........................................................

x• Agitation• Aggression• Psychosis

May consider AChEI
e.g. donepezil

Consider rivastigmine

Frontotemporaldementia- Psychosocial intervention is the first line treatment- Antidepressant in depressed patients- Consider anxiolytic in patients with severe anxiety
symptoms• Depression• AnxietyCo-morbid emotional disorders

Behavioural and Psychological Symptoms of Dementia (BPSD)

Donepezil
and/or memantine

Moderately severe
to severe...........................................................

- Psychosocial intervention is the first line treatment- Consider antipsychotics if symptoms are distressing
and other treatment measures failed. Avoid in DLB

AChEI

Mild to moderate

e.g.antihypertensive, anti- lipid, anti-diabetic and anti-platelet

Dementia of Lewy
Body (DLB) /Parkinson
Disease Dementia

Pharmacological Intervention

PATIENT WITH DEMENTIA

ALGORITHM FOR MANAGEMENT OF DEMENTIA...........................................................

LEVELS OF EVIDENCE
I

Evidence obtained from at least one properly designed
randomized controlled trial

II-1

Evidence obtained from well-designed controlled trials
without randomization

II-2

Evidence obtained from well-designed cohort or case-control
analytic studies, preferably from more than one center or
research group

II-3

Evidence obtained from multiple time series with orwithout the intervention. Dramatic results in uncontrolled
experiments (such as the results of the introduction of
penicillin treatment in the 1940s) could also be regarded as
this type of evidence.

III

Opinions of respected authorities, based on clinicalexperience; descriptive studies and case reports; or reportsof expert committees.

SOURCE: US/CANADIAN PREVENTIVE SERVICES TASK FORCEGRADES OF RECOMMENDATIONAAt least one meta analysis, systematic review, or RCT, orevidence rated as good and directly applicable to the target
population

B

Evidence from well conducted clinical trials, directly applicableto the target population, and demonstrating overall consistencyof results; or evidence extrapolated from meta analysis,
systematic review, or RCTC

Evidence from expert committee reports, or opinions and/or clinical experiences of respected authorities; indicatesabsence of directly applicable clinical studies of good quality

SOURCE: MODIFIED FROM THE SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK (SIGN)

xi

xii

TABLE OF CONTENTSGUIDELINE DEVELOPMENT AND OBJECTIVESI

GUIDELINE DEVELOPMENT GROUPV

REVIEW COMMITTEE 		

VI

EXTERNAL REVIEWERS		VII

ALOGORITHM ON SCREENING OF DEMENTIA IN PRIMARY CARE

VIII

ALGORITHM FOR DIAGNOSIS OF DEMENTIA AT SECOMDARY /TERTIARY LEVELIX

ALGORITHM FOR MANAGEMENT OF DEMENTIA

X

1.0 INTRODUCTION 			1

1.1

INDIDENCES AND PREVALENCES

1

1.2

GENERAL CLINICAL FEATURES

2

1.3

SUBTYPES			2

		

1.3.1 Alzheimer disease3		

1.3.2 Vascular Dementia3		

1.3.3 Lewy Body Diseases3		

1.3.4 Frontotemporal dementia5		

1.3.5 Mixed Dementia

5

DIFFERENTIAL DIAGNOSIS

6

1.4

2. 0 PREVENTION, RISK FACTORS AND EARLY IDENTIFICATION
2.1	non- modifiable risk factors	

7
7

		

2.1.1 Age			7		

2.1.2 Gender		7		

2.1.3 Genetic		

8		

2.1.4 Intellectual Disability and Down syndrome

2.2 POTENTIALLY MODIFIABLE RISK FACTORS			 2.2.1 Cardiovascular Risk factors
			 2.2.2 Lifestyle risk factors
			 2.2.3 Medication					
3.0 EARLY IDENTIFICATION OF DEMENTIA

xiii

9
10
10
14
19
22

4.0 ASSESSMENT AND DIAGNOSIS
4.1		 ASSESSMENT AT PRIMARY CARE
			 4.1.1 Routine cognitive screening
			 4.1.2 Screening instruments for people at risk of dementia
		 4.1.3 Refferral of patients with dementia to specialist services				(secondary/tertiary level)
4.2 MEMORY CLINIC		
4.3 ASSESSMENT OF DEMENTIA AT THE SECONDARY/ TERTIARY CARE LEVEL
4.3.1 History Taking
			 4.3.2 Physical examination
			 4.3.3 Brief cognitive tests
			 4.3.4 Neuropsychological test			 4.3.5 Assessment of behaviour and Psychological Symptoms of Dementia
			 4.3.6 Assessment of functional impairment
4.4		 DIAGNOSTIC CLASSIFICATION

23
23
23
24
26

			 4.4.1 Diagnostic criteria for dementia subtypes

38

27
29
30
30
30
34
35
37
38

4.5

Progression and severity of dementia

41

4.6

Screening for co-morbid medical conditions

43

4.7

Neuroimaging		

44

			 4.7.1 Structural neuroimaging

44

			 4.7.2 Functional Imaging

46

4.8

Electrocephalogram		

48

4.9

Biomarkers			

48

			 4.9.1 CSF biomarker

48

			 4.9.2 Plasma biomarker

50

5.0 pharmacological intervention	

52

COGNITIVE ENHANCERS

52

			 5.1.1 Alzheimer Disease

5.1

53

		 5.1.2 Vascular dementia

57

			 5.1.3 Lewy Body Disease (Dementia with Lewy Body/
				
Parkinson disease dementia)
5.1.4 Frontotemporal dementia (FTD)

59
60

			 5.1.5 Mild Cognitive impairment

61

5.2 DRUGS TO CONTROL BEHAVIOURAL AND
			 PSYCHOLOGICAL SYMPTOMS OF DEMENTIA (BPSD)

63

			 5.2.1 Treatment of Agitation, Aggression and Psychosis

63

xiv

5.3

TREATMENT OF DEPRESSION AND MOOD SYMPTOMS

69

			 5.3.1 Antidepressants69

			 5.3.2 Mood stabilisers

70

5.4

COMBINATION THERAPY70

			 5.4.1 Combination of AChEI with memantine70

			 5.4.2 Combination AChEI with SSRI (Serotonin Augmentation)

71

			 5.4.3 Combination AChEI with multivitamin supplement71			 5.4.4 Combining AChEI with non pharmacological intervention

71

5.5

ALTERNATIVE/COMPLEMENTARY DRUGS

72

			 5.5.1 Ginkgo biloba

72			 5.5.2 Omega-3 fatty acid73

			 5.5.3 Folic acid and vitamin B

74

			 5.5.4 Vitamin E		

75

			 5.5.5 Huperzine A

75

6.0 NON-PHARMACOLOGICAL TREATMENT OF DEMENTIA

77

6.1
		

MAINTENANCE OF FUNCTIONS

78

6.1.1 Strategies for promoting independence78			 6.1.2 Maintenance of cognitive functions
6.2

MANAGEMENT OF BEHAVIOUR THAT CHALLENGES AGITATION, AGGRESSION AND PSYCHOSIS

82
84

			 6.2.1 Behavioural management approaches

84			 6.2.2 Music therapy85			 6.2.3 Physical activity mobility programme86			 6.2.4 Validation therapy86			 6.2.5 Multisensory stimulation and /or Snoezelen therapy87			 6.2.6 Massage and touch therapy87			 6.2.7 Aromatherapy87			 6.2.8 Light therapy

88

6.3

REDUCTION OF CO-MORBID EMOTIONAL DISORDERSANXIETY AND DEPRESSION

7.0 CARE ENVIROMENT		
7.1

91

ENVIROMENTAL DESIGNS FOR PEOPLE WITH DEMENTIA

8.0 INTERVENTIONS FOR CAREGIVERS
8.1

89
91
93

EDUCATIONAL INTERVENTION IN THE MANAGEMENT OFPEOPLE WITH DEMENTIA AND THEIR CAREGIVERS

xv

97

9.0 BASIC LEGAL AND ETHICAL ISSUES
9.1 DISCLOSURE IN DEMENTIA OR TRUTH TELLING
9.2 CAPACITY AND DECISION MAKING
9.3 PALLIATIVE AND END of LIFE CARE FOR PEOPLE WITH DEMENTIA
		
9.3.1 Artificial nutrient and hydration
			 9.3.2 Pain						 9.3.3 Treatment of Infection
			 9.3.4 Restraint					 9.3.5 Cardio-pulmonary resuscitation

98
98
100
101
101
102
104
104
105

References				106

Appendix 1

SEARCH strategy	

121

Appendix 2

CLINICAL QUESTION

124

Appendix 3

Malay Mini Mental State Examination

127

Appendix 4

THE ICD -10 CLASSIFICATION OF MENTAL AND BEHAVIOURAL DISORDERS 129

Appendix 5		 DSM-IV CLINICAL CRITERIA FOR DIAGNOSIS OF DEMENTIA

131

Appendix 6		 DIAGNOSTIC CRITERIA FOR DEMENTIA OF THE ALZHEIMERS TYPE
( based on DSM-IV-TR)

132

Appendix 7		 DISCLOSURE OF PROGNOSES AND DIAGNOSES

134

Appendix 8

ACETYLCHOLINESTERASE INHIBITOR

135

Appendix 9 N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST		 (Micromedex®Healthcare Series, vol 141 version 2009)

136

Appendix 10 ANTIPSYCHOTIC
		 (Micromedex®Healthcare Series, vol 141 version 2009)

137

Appendix 11 ANTIDEPRESSANT

138

Appendix 12 ENVIROMENTAL DESIGNS APPROPRIATE FOR PEOPLE WITH DEMENTIA 139
Appendix 13 EDUCATIONAL INTERVENTION IN THE MANAGEMENT OF PEOPLE WITH
		 DEMENTIA AND THEIR CAREGIVERS
140
Appendix 14 WHO PAIN LADDER141

LIST OF ABBREVIATIONS		ACKNOWLEDGEMENT			DISCLOSURE STATEMENT		SOURCES OF FUNDING			

142
144
144
144

xvi

1.0

INTRODUCTION

Dementia is a syndrome characterised by diverse behavioural, cognitive andemotional impairments. The Royal College of Physicians of London, defined
dementia as an acquired global impairment of higher cortical functions
including memory, capacity to solve problems, learned percepto-motor skills,social skills, language and communication, and control of emotion, in theabsence of clouding of consciousness. [1] The associated features of dementia
include behaviouraland psychological symptoms. These symptoms can occur
at any stage of the illness, and may be the most likely reason for people
with dementia (PWD) being brought for medical attention. The condition isprogressive though not necessarily irreversible. It has been reported that
15% of people with dementia have a potentially treatable cause, but theprevalence of reversible dementia is only 1%.[2],[3]1.1

INCIDENCE AND PREVALENCE

It is estimated that there are 24.3 million people with dementia worldwide,with 4.6 million new cases each year. The number of people affected
is expected to double every 20 years. The forecasted rate of increase isestimated to be more than 300% in India, China and their South Asian andWestern Pacific neighbours. About 6.1% of the population 65 years of age
and older, suffer from dementia (about 0.5% of the worldwide population).
Fifty nine percent of PWD are females. [4],[5]There have been few prevalence studies of dementia in Malaysia. A community
survey (n=223) amongst Malays aged 60 years and above in Selangor, found that
24% were cognitively impaired.[6] Another study (n=522) found the prevalence of
dementia in an urban community of Malays (aged 60 years and above) in Kuala
Lumpur was 6%.[7] A large community study of the elderly in Malaysia (n=2980,
aged 60 years and above) yielded a prevalence of organic mental disorder(inclusive of dementia) at 14.4%. [8].Among those living in the government
residential homes, the prevalence of probable dementia are higher, at 36.5%.[9]In the United States Health Retirement Study (HRS), the prevalence of AD, VaD
and all dementia increased with age, reaching 37.4% dementia prevalence
among individuals aged 90 and older. [10]1

1.2GENERAL CLINICAL FEATURES

The symptoms of dementia may be divided into two major groups-the cognitive
and non-cognitive symptoms.
The cognitive symptoms comprise of memory impairment especially learningof new material, which is the most prominent early symptom. Previously learned
material may be lost in more severe dementia. Language may also be affected.
Individuals may have difficulty with spatial tasks, such as navigating aroundthe house or in the immediate neighborhood. Poor judgment and poor insightare also common. These cognitive deficits must be sufficiently severe to cause
impairment in occupational or social functioning and must represent a decline
from a previous level of functioning. The order of onset and relative prominenceof the cognitive disturbances and associated symptoms vary with the specific
type of dementia.
The non-cognitive symptoms encompass the neuropsychiatric symptoms(NPS) or the behavioural psychological symptoms of dementia (BPSD). The
behavioural component includes verbal or physical agitation, aggressive andnon-aggressive behavior which can be verbal or physical, such as wandering,disinhibition, sundowning syndrome, and others. The most common
psychological symptoms are depression, sleep disturbances, and psychotic
symptoms (delusions of persecution and misidentification, and hallucinations).
Anxiety is fairly common, and some patients manifest “catastrophic reactions,” anoverwhelming emotional responses to relatively minor stressors such as changes
in routine or environment. Dementia is sometimes accompanied by motor
disturbances, which may include gait difficulties, slurred speech, and a variety
of abnormal movements. Other neurological symptoms, such as myoclonus andseizures, may also occur.

1.3

SUBTYPES

The clinical diagnoses of dementia rely mostly on recognizing patterns ofneurological and cognitive impairment, rather than on specific biomarkers orother laboratory approaches. Diagnostic problems arise because the neurologicalfindings are usually non-specific, and the cognitive profiles may overlap.
21.3.1

Alzheimers disease

Alzheimers disease (AD) remains the most common type of the primarydegenerative dementia, accounting for 60-80% of cases. [11] It is characterised
by progressive deterioration of short term memory and other higher cortical
functions. Motor skills are generally preserved until late in the disease. Supportivefeatures include altered behaviour and inability to carry out activities of daily living(ADL). It predominantly affects the older age group (> 65 years), but early onset
can occur. A clinical diagnosis of AD can be made accurately in 90% of cases,
but diagnosis can only be confirmed on brain biopsy by the presence of neuritic
plaques (NPs), which are the accumulated deposits of amyloid B40 and amyloid
B42, and neurofibrillary tangles (NFTs), the hyperphosphorylated tau proteins. The
severity of the cognitive decline is more closely related to the NFTs burden. It is
yet unknown what triggers the changes in the neurons.

1.3.2

Vascular Dementia

The term vascular cognitive impairment covers a broad range of cognitive deficits
from mild impairment to dementia, that can be associated with vascular factors.
[331]
However, in this guideline, the focus will be limited to only vascular dementia.
Vascular dementia (VaD) is a heterogeneous disease with diverse vascularpathologies, such as strategic infarcts, multiple cortical infarcts, andsubcortical ischaemic lesions.[12] Major cardiovascular risk factors are independentrisk factors for the development of atherosclerosis and vascular dementia. Theserisk factors also predispose to acute stroke, which is a well established factor forthe development of VaD. [13] The Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leucoencephalopathy (CADASIL), an early genetic smallvessel disease that causes lacunar strokes, ischaemic white matter lesions, andsubcortical ischaemic vascular dementia has also been described.[12]1.3.3

Lewy Body Diseases

Lewy bodies are eosinophilic cytoplasmic inclusions from damaged cytoskeletalcomponent that contain deposits of a protein called alpha-synuclein. [14] Lewy
bodies are present in both Parkinson disease dementia (PDD) and
Lewy body dementia (DLB) with some differences in their distribution.
In Parkinson disease it is found primarily in the subcortical regions of the brain, themidbrain, substantia nigra and locus ceruleus. In contrast, DLB is characterized by thepresence of Lewy bodies in the subcortical and cortical (frontotemporal) regions of thebrain. Amyloid plaques can also be found in DLB.[15] Both PDD and DLB belonged to
the group called the “synucleinopathies”. [16]3

a. Dementia with Lewy Bodies (DLB)
Dementia with Lewy bodies (DLB) account for 15-25% of dementia cases
at autopsy. [17],[18] The cardinal features of dementia with Lewy bodies are:dementia, delirium (fluctuating cognition), early and vivid visual hallucinations
and Parkinsonism. Any two of the supportive features of repeated falls,
syncope, transient disturbances of consciousness, neuroleptic sensitivity,
systematised delusions and/or hallucinations in other modalities, further
strengthens the diagnosis. DLB is a distinct pathology, though there are
overlaps between DLB and PDD, and DLB and AD.[19] In DLB, the onset ofdementia and parkinsonism must occur within one year of each other, andeither feature can be the initial symptom.[20] In PDD the motor features ofparkinsonism predate the dementia by many years.
Dementia with Lewy bodies (DLB) differs from AD in that patients with DLB tend tohave more problems with executive functions (planning, prioritizing, sequencing)and visuospatial impairment, but they tend to perform better with verbal memory.
Both can co-exist, and diagnosis can be difficult as neither neuropsychologicaltesting nor neuroimaging can reliably differentiates DLB from AD with accuracy.[21]b. Parkinson Disease Dementia
The prevalence of dementia in patients with Parkinson disease is six times higher
than in the general population. The prevalence of dementia in patients with PD
was 24–31% and that 3–4% of the dementia in the general population is due to
PDD. The estimated prevalence of PDD in the general population aged 65 years
and older is 0.2–0.5%.[13] The development of PDD is associated with a two foldincreased in mortality, caregiver stress, nursing home admission, and reduced
quality of life.[22] There is usually a 10 to 15 year lag time between the Parkinson
diagnosis and the onset of dementia.[13]41.3.4

Frontotemporal Dementia

Frontotemporal dementia (FTD) is the most common cause of Frontotemporal
Lobar Degeneration, a frequent cause of dementia in younger individuals withdisease onset <65 years (mean age of onset is 52.8 to 56 years).[23],[24] It ischaracterized by behaviouralchanges and a dysexecutive syndrome. The othertwo syndromes in Frontotemporal Lobar Degeneration are: Semantic Dementia
and Primary Non-fluent Aphasia, which feature language dysfunction andvariable behaviouralabnormalities. Frontotemporal dementia (FTD) and Semantic
Dementia each account for 40% of the Frontotemporal Lobar Degeneration, andPrimary Non-fluent Aphasia accounts for the remaining 20%. [25] Frontotemporal
Lobar Degeneration accounted for 20% of all cases of dementia [26]. About 38%
to 40% of Frontotemporal Lobar Degeneration has a genetic component, of which
80% have an autsomal dominant pattern of inheritance.[27] Frontotemporal Lobar
Degeneration is caused by the progressive dysfunction of the frontal and/or
temporal lobes, with unilateral or bilateral involvement. Features that differentiate
it from AD include social misconduct, hyperorality or akinesia and absence ofperceptual disturbances. Memory is not predominantly affected.[28]1.3.5

Mixed Dementia

There is increasing evidence that the brain lesions associated with AD and
VaD often occur together. This coexistence of AD and VaD pathology is often
termed mixed dementia. In an autopsy series from dementia clinics, it wasreported that coexisting vascular pathology occurs in 24% to 28% of AD
cases. Patients with mixed dementia are usually older and have more medical
co-morbidities. The diagnosis and treatment of patients with both AD and
VaD brain pathology is complex due to the lack of consensus on appropriate
clinical criteria and terminology.[29] The term can also include other coexisting
pathologies. Pathological Parkinson disease is present in 20% of patientswith AD, and about 50% of patients with DLB have AD pathology. [30] ,[31]

5

1.4

DIFFERENTIAL DIAGNOSISDementia has to be differentiated from delirium and depression. Either condition
may co-exist with dementia (refer Table 1).

Table 1: Differentiating dementia, depression and delirium
SYMPTOMSDEMENTIA

DEPRESSION

DELIRIUM

Onset

Insidious

GradualAcute

Duration

Months/years

Weeks/Months

Hours/days/weeks

CourseGradually progressive

Worse in morning andimproves at night

Fluctuates. Worse atnight. Lucid period

Alertness

NormalNo interest.
Responds usually as“don’t know”

Fluctuates

Orientation

Usually impaired fortime and place

Usually normal

Always impaired

MemoryImpaired recent andsometimes remotememoryRecent memory may
be impaired. Remotememory intact

Impaired recent
memoryThoughts

Slowed, perseverance

Slowed, preoccupied,
sad and hopelessOften out of touch withreality

Perception

Often normal
20% with mood
Visual hallucinations in congruent
30-40%
hallucinations

EmotionApathetic, labile,
irritable

Sleep

Disturbed, nocturnal
Early morning
wandering or confusion awakening

OthersVisual and auditory
hallucinations arecommonFlat, sad, unresponsive. Irritable, aggressive or
May be irritablefearful

Past history or family
history of mood

Nocturnal confusion
Other physical diseaseobvious

Adapted from ‘Dementia touches everyone -a training guide for GPs’.[32]A relationship between symptoms of Obstructive Sleep Apnea (OSA) and cognitive
impairment has been identified in patients with dementia. [33] Patients with severe
dementia were found to have significantly more severe obstructive sleep apnea,
and those with more severe obstructive sleep apnea had significantly more
severe dementia.[34]62.0 PREVENTION, RISK FACTORS & EARLY IDENTIFICATION
It has been estimated that delaying the onset of dementia by five years would
half its prevalence.[35] Hence prevention of dementia must be an ultimate
goal. There has been much research into the prevention in dementia, but forany preventive strategies to be effective, several considerations need to belooked into:

Preventive strategies:r Knowledge about risk factorsr Identifying the non-modifiable and the potentially modifiable risk factors,
andr Evidence that modifying the potentially modifiable risk factors could
reduce the incidence of dementia(NICE 2006) [13]2.1

NON-MODIFIABLE RISK FACTORSThe confirmed risk factors for dementia are age and gender, which are notmodifiable. Genetic/family history of dementia, intellectual disability and Down
syndrome are also non–modifiable risk factors. [36]

2.1.1

Age

Advancing age remains one of the few confirmed risk factors for the developmentof dementia. The other confirmed risk factors are genetic, APOEε4 and Down
syndrome. Prevalence of dementia doubles for every 4-5 years after the ageof 65 years and those for VaD doubled every 5.3 years.[13] In a population study(n=1931), age ≥ 65 years was a risk factor for any dementia (Odds ratio (OR) =1.1)
and for AD (OR=1.2). [37]2.1.2

GenderPrevalence studies show higher rates in women, especially for AD. The risk for
all dementia and AD for the female sex was OR=1.7 and OR=2.0, respectively.
[37]. Rates for VaD are higher in men, though the rates for women will equalise atolder ages.[36]72.1.3

Genetic

Early onset AD is generally defined as occurring before 60 years of age. It
accounts for only 6%–7% of all cases of AD. Of this group, only 13% clearly
exhibit autosomal dominant transmission. Early onset autosomal dominant formsof AD account for 1% of AD cases. [38]Three causative gene mutations are identified; amyloid β-protein precursor(AβPP) on chromosome 21, presenilin 1(PS1) on chromosome 14 and presenilin2(PS2) on chromosome 1. Among families in which causal genetic mutations
for Early onsetAD have been identified, 30%–70% of mutations are in thepresenilin-1 gene, 10%–15% are in the amyloid precursor protein gene, and lessthan 5% are in the presenilin-2 gene.[39]No single causative genetic mutation has been identified for late onset
AD. Most cases are a complex influence of genetic risk factors (e.g., theapolipoprotein E gene [APOE], sortilin-related receptor 1 gene [SORL1]) andenvironmental risk factors. APOE ε4 is the only robustly established risk
factor for late onset AD. [40] Level III, fair
A systematic review of five population studies reported that APOE ε4 significantly
increased the risk. The findings of APOE ε2 as reducing risk of dementia were
not as robust. Only 2 studies were identified and the results were inconsistent.
[41] Level II-3, fair

The strength of the association between the APOE ε4 allele and AD isstronger among women and people between 55 and 65 years old, but less soamong older people. This may be because the risk of AD rises sharply in older
age. Given all these uncertainties, genetic screening for the APOE genotype
in asymptomatic individuals in the general population is not recommended
due to low specificity and sensitivity. [39] Level III, good Patients suspected of having
familial Early onsetAD should, however be referred to a memory or genetic
clinic for further evaluation.[39] Level III, good

Recommendation
Genetic screening should only be done in a research setting. (Grade C)8

2.1.4

Intellectual Disability and Down syndrome:a. Intellectual disability (excluding Down syndrome)
The prevalence of dementia in people with learning disabilities without Down
syndrome is raised to two to three times that expected in those aged over
65 years. Learning disability is an established non-modifiable risk factor for
dementia. [13] , Level I, good)
In a recent epidemiological survey (n=228) of people with intellectual disability
without Down syndrome aged 60 years and older, 28 patients (12.3%) met atleast one set of dementia criteria.[42] Level III, fair
Dementia is common among people with intellectual disability.

b. Down syndrome
People with Down syndrome are at risk of developing dementia of Alzheimer type
about 30-40 years earlier than the rest of the population. [13] Level I, good
In a cohort study of people with Down syndrome (n=506) aged 45 years andabove, the prevalence of dementia over a period of four years was studied. It was
found that up to the age of 49 years the prevalence was 8.9% (95% confidence
interval (CI) 5% to 12%). The prevalence rate for the age group of 50-54 years
was 17.7% (95%CI 12% to 23%), 55-59 years, 32.1% (95%CI 22% to 42%),and for 60 years and above the prevalence was 25.6% (95%CI 12% to 40%). [43]Level II-3, fair

Another cohort study followed up hospitalised adults with Down syndrome (n=92)
for 15 years. Of the 87 participants who were dementia-free at the onset, 18 (21%)
patients developed dementia during follow-up, with a median age of onset of 55.5
years. At the age of 60 years and above, a little more than 50% of patients still alive
had clinical evidence of dementia. [44] Level II-2, fair
Down syndrome is an established risk factor for the development of dementia.
9

2.2

POTENTIALLY MODIFIABLE RISK FACTOR

The pathogenesis behind the aetiology of dementia involves several underlying
mechanisms leading to neuronal loss and cell death. These mechanisms include
the inflammatory hypothesis, role of antioxidants, ‘use it or lose it’ hypothesis
and others. The potential effects of nutrition have become a topic of increasing
scientific interest. There are arguments that nutrients such as vitamins, traceminerals, lipids can affect the risk of cognitive decline and dementia especially infrail elderly people at the risk of deficiencies.
These potentially modifiable risk factors will be grouped under three main
headings:r

Cardiovascular risk factors: high blood pressure (hypertension),
hypercholesterolemia, diabetes mellitus, folate and high homocysteinelevelsr		Lifestyle risk factors: obesity/being overweight, alcohol use, smoking, head

injury, physical activity and education/mental stimulationr

Medication: NSAIDs, statins and antioxidants.

2.2.1

Cardiovascular Risk Factors

Major cardiovascular risk factors such as hypertension, smoking,hyperlipidaemia and diabetes are independent risk factors for the development of
atherosclerosis and VaD. These risk factors also predispose to acute stroke, whichitself is a well established risk factor for the development of vascular dementia.
Indeed, cardiovascular risk factors are known to associate with dementia of allclinical types. [13] Level I, good
The Singapore guideline highlighted the fact that vascular risk factors should beconsidered and treated. [45] Level III, good10

a. Hypertension
A systematic review and meta-analysis of four studies on hypertension
demonstrated that there was a non-significant trend (relative risk
(RR)=0.8, 95%CI 0.6 to 1.0) towards a reduction in dementia among treatedsubjects. This suggests that antihypertensive treatment may be a promisingavenue for prevention of dementia, including AD and VaD. Furthermore there
are already many evidence-based reasons for treating hypertension apartfrom reducing dementia risk. This includes reducing cardiovascular andcerebrovascular events. [13] Level I, goodHypertension in the Very Elderly Trial Cognitive Function Assessment(HYVET-COG) showed there was no significant difference between treatment
and placebo groups (hazard ratio (HR) 0.9, 95%CI 0.7 to 1.1). When thesedata were combined in a meta-analysis with other placebo-controlled trialsof antihypertensive treatment, the combined risk ratio favoured treatment(HR 0.9, 95%CI 0.8 to 1.0, p=0.045).[46] Level I, fair
In a recent systematic review of 16 longitudinal observation studies, a significant
association between hypertension and risk of AD was reported, but this wasachieved only by changing the criteria of hypertension, including altering thecriteria levels for systolic (≥140 mmHg) and diastolic (both lower and higher) or
changing the length of the observation (midlife). APOE 4 was the most consistentrisk factor interacting with hypertension. The association with diabetes further
increased risk. [41] Level II-2, good

Recommendation
Hypertension, occurring at mid-life (40-60 years) is a risk factor for dementia
and should be appropriately treated. (Grade A)

b. Diabetes Mellitus
Diabetes is an established cardiovascular risk factor and is associatedwith mortality and significant morbidity. Emerging data suggests that
diabetes mellitus is also a risk factor for dementia and cognitive decline
in older persons.
11A Swedish Health Technology Assessment report concluded that the evidence
linking diabetes to dementia is moderately strong.[47] Level I, good A recent systematic
review of 17 cohort studies found the relationship between diabetes and riskof AD to be complex. Most studies reported no significant association between
diabetes and incident AD and few reported only a modest effect. It is only when
diabetes is considered in association with other factors, particularly hypertension,that significant associations are reported. [41] Level II-2, good
A recent meta-analysis of 15 prospective cohort studies showed that the pooled
adjusted risk ratio (RR) for all dementia when persons with diabetes were compared tothose without, was 1.5 (95%CI 1.3 to 1.7). Summary RRs for AD and VaD comparing
persons with diabetes to those without diabetes were 1.4 (95%CI 1.2 to 1.7) and2.4 (95%CI 1.8 to 3.2), respectively. It was found that diabetes was associated witha 47% increased risk for all dementia, 39% for Alzheimers dementia, and more than
two-fold risk for vascular dementia, among the community dwelling older adults. The
association of diabetes to dementia was independent of cardiovascular co-morbidities. The
results of the association between diabetes medications and risk of dementia were tooheterogeneous to be conclusive. [48] Level II-2, good

Recommendation
Diabetes mellitus is a modifiable risk factor for the development ofdementia and should be appropriately treated. (Grade C)

c. Hypercholesterolemia
Hypercholesterolaemia is a recognised risk factor for stroke, itself a major risk for
VaD. Raised cholesterol level has also been implicated in AD.
A systematic review of 18 cohort studies (n=25,682), follow-up range 4.8-29
years (mean 13.3) looked at the association of total cholesterol and risk of AD,
VaD and cognitive decline. It was noted that there was a consistent association
between high midlife total cholesterol and risk of AD and any dementia. No study
reported a significant association between midlife total cholesterol and VaD.
The meta-analyses of late-life total cholesterol in relation to AD, VaD, and any
dementia, did not reveal any significant association, suggesting the possibility
that the effect of total cholesterol on dementia risk may be limited to midlife.
There was only weak evidence for an association between total cholesterol andcognitive decline.[49] Level II-2, fair
There is insufficient evidence that hypercholesterolaemia increases the risk of dementia.
12

d. Homocysteine, vitamin B12, vitamin B6 and folic acid
Homocysteine, vitamin B12 and folate have been linked to cognition, dementia
and mood. Deficiency in either vitamin leads to an increase in total serum
homocysteine concentrations, and high homocysteine levels was found to disturb
brain metabolism, as well as increased the risk of atherosclerosis and CVD. The
prevalence of vitamin B12 deficiency in the elderly is 20%. Folate deficiency
primarily caused by dietary deficiency is also common (10% prevalence) among
the frail elderly population.[50]The NICE guideline stated that raised homocysteine levels, associated with low
folate intake and low folate levels, increased the risk of dementia, including AD.
There is much interest in whether supplementation with B12 and/or folate may
prevent the development of dementia and perhaps slow its progression. However
supplementation has not shown any positive results. It remains a potentiallymodifiable risk factors [13] Level I, goodA Cochrane review on folic acid with or without vitamin B12 in the prevention ofdementia (one RCT) and cognitive decline (three RCTs) provided no consistentevidence on the role of folic acid in dementia prevention. However the studies
were too heterogenous to be conclusive.[51] Level I, fair
Vitamin B12 was not efficacious in reducing the risk of dementia and cognitive
decline. This was based on a systematic review of three RCTs (three months
duration) of healthy elderly and patients with dementia who were given vitamin
B12 supplementation versus placebo.[51] Level I, fair
Another homocysteine related vitamin is vitamin B6 (pyridoxine). A Cochranereview of two RCTs of the effect of vitamin B6 on healthy elderly (n=297) against
placebo over a period of 5-12 weeks, concluded that vitamin B6 had no overall
effects on cognition or mood.[52] Level I, poor

Recommendation
Folic acid supplement, vitamin B6 or vitamin B12 should not be used for theprevention of cognitive decline or dementia. (Grade B)
13

2.2.2

Lifestyle risk factors

a. Smoking
Large prospective epidemiological studies have established that smoking is a risk
factor for dementia in general and AD in particular. Smoking is clearly a risk factor
for cardiovascular and cerebrovascular disease and as such increases the risk forstroke and vascular dementia.[13] Level I, good
In a more recent meta-analysis of prospective studies (n=19), it was found thatelderly current smokers were at increased risk of dementia. Compared with neversmokers, current smokers had 1.8 times (95%CI 1.4 to 2.2) risk of incident AD,
1.8 times (95%CI 1.3 to 2.5) risk of incident vascular dementia, and 1.3 times(95%CI 1.0 to 1.6) risk of any dementia. They also found that, compared withformer smoking, current smoking was a significant risk factor for AD (RR 1.7,
95%CI 1.3 to 2.3) but not for VaD (RR 1.26, 95%CI 0.6 to 2.6) or any dementia(RR 1.3, 95%CI 1.0 to 1.8).[53] Level II-2, good
Another cohort study (n=6868) also found that current smoking at baseline
was associated with an increased risk of dementia (HR 1.5, 95%CI 1.2 to1.9) and AD (HR 1.6, 95%CI 1.2 to 2.0) when compared with never smokers.
There was no increased risk for VaD (HR 1.4, 95%CI 0.7 to 2.8) found. There
was also no association found between past smoking and risk of dementia(HR 1.2, 95%CI 1.0 to 1.4), AD (HR 1.2, 95%CI 0.9 to 1.4) or VaD (HR 1.2,
95%CI 0.7 to 2.2).[54] Level II-2, fair)
Smoking is a modifiable risk factor for dementia.

Recommendation
Smoking cessation is strongly advocated. (Grade A)

b. Alcohol consumption
Excessive alcohol consumption is an established risk factor for dementia.
Epidemiological studies have shown that moderate alcohol consumption isassociated with lower rates of dementia compared to either heavy drinking or
abstinence. There is no consistent evidence to show that one type of alcoholic
drink is more protective than another. [13] Level I, good14

A more recent cohort study of over 16 years duration, found that any intake ofalcohol predicted a 34% lower risk (HR 0.7, 95%CI 0.5 to 0.9) of developing
dementia. Compared with those who are abstinent, the risk of developing dementia(HR) for those taking: 1-7 standard drinks per week were 0.7 (95%CI 0.5 to 0.9);
0.7 (95%CI 0.5 to 1.0) for 8-14 drinks per week ; and 0.4 (95%CI 0.2 to 0.8) for
15-28 drinks per week. [55] Level II-3, fair The general medical recommendation for safe
drinking is up to 14 standard units per week for females and 21 standard units
per week for males. [56], Level III, good
In a 34 year cohort study of women, (n=1462) consumption of wine was found to
be protective for dementia (HR 0.6, 95%CI 0.4 to 0.8). [57] Level II-2, fairA recent systematic review include a meta-analyses of 15 prospective
studies (follow-ups ranged from 2 to 8 years).The participants comprised of
AD (n=14,646), VaD (n=10,225) and any dementia (n=11,875). It was foundthat among older adults, light to moderate alcohol intake was associatedwith a 25%–28% reduction in risk of AD, VaD, and any dementia comparedwith alcohol abstinence. The pooled relative risks (RRs) of AD, VaD, and any
dementia for light to moderate drinkers compared with nondrinkers were0.7 (95%CI 0.6 to 0.9), 0.8 (95%CI 0.6 to 1.0), and 0.7 (95% CI 0.6 to0.9), respectively. [333] Level 1,fair
Excessive alcohol consumption is a modifiable risk factor for dementia.

Recommendation
Excessive consumption of alcohol should be discouraged. (Grade C)
c. Obesity
Increased Body Mass Index (BMI) and increased body adiposity have been linked
to increased risk of developing dementia. Several prospective studies havedemonstrated an association between raised body mass index in mid life and anincreased risk of dementia in general, and AD in particular. Obesity also increases
the risk of developing type-II diabetes, which itself is a modifiable risk factor forthe development of dementia. [13], Level I, goodA systematic review of four cohort studies (n=22,861) with a long follow-up
of at least 20 years showed that elevated body mass index was associatedwith significant increased risk of dementia. [59] Level II-2, fair15

A meta-analysis of seven prospective cohort studies of older adults
demonstrated that the pooled OR for obesity and incident AD was 1.8 (95%CI
1.0 to 3.3), while that for obesity and VaD was 1.7 (95% CI 0.5 to 6.3).
This study showed a moderate association between obesity and the risk fordementia and AD. [60] Level II-2, good

Recommendation
Obesity is a modifiable risk factor and maintenance of normal body massindex is recommended. (Grade C)

d. Head injury
Head injury is associated with loss of consciousness almost doubles the risk ofdementia. However, a meta-analysis of 15 epidemiological studies demonstrated
that this effect was specific to males only. [13] Level I, good
Mild to moderate traumatic brain injury was not associated with higher
rates of amnestic mild cognitive impairment or dementia. The presenceof APOE ε 4 in traumatic brain injuries was not associated with cognitivechanges. [61] Level II-2, good
For APOE ε4 allele-carriers, even fall-related head injuries which are notassociated with explicit traumatic brain injury (TBI), was associated with anincreased risk of dementia (HR 2.7, 95%CI 1.0 to 7.2).[62] , Level III, fair
Head injury associated with loss of consciousness is a risk factor for dementia

Recommendation
Road and occupational safety measures are recommended. (Grade A)

e. Exercise
There have been several population based studies on the association of
exercise and dementia but no RCTs undertaken to investigate whether
starting to engage in exercise for those who currently do not, will reduce
their risk of developing dementia. It was concluded that there was insufficientevidence to recommend physical activity specifically as a preventive measurefor dementia. [13] Level I, good ;[63] Level I, good)16

A recent RCT (n=170) on volunteers who had subjective memory
complaints but did not meet the criteria for dementia, were assigned
to regular exercise for a duration of 24 weeks (150 minutes per week)
versus usual care. It was found that the participants in the exercise group
improved by 0.3 points (95%CI -0.9 to 0.5) and those in the usual caregroup deteriorated by 1.0 (95%CI 0.3 to 1.8) on the ADAS-Cog at 24
weeks. At the end of 18 months the participants in the intervention group
improved by 0.7 points (95%CI -1.3 to 0.0) and the usual care group
improved by 0.1 points (95%CI -0.5 to 0.9). [64] Level I, good
There is insufficient evidence that exercise reduced the risk of developing dementia.

f. Education and mental stimulation
Findings from two long-running studies of ageing and cognition, the Nun study
and Religious order Study, have revealed that education helps protect people fromthe effects of AD. The more years of education, the greater the cognitive reserve.
The likelihood that more poorly educated subjects will adopt unhealthy lifestyle
behaviours has been suggested as an explanation for the stronger association
found in subjects with types of dementia other than AD.
Lower educational attainment may be linked to subsequent development ofdementia while cognitive training and participation in cognitively demanding
leisure activities, may reduce risk of dementia. [13] Level I, good
A cohort study of non-demented subjects (n=931) on mentally stimulating
activities at work, found that complex work, in particular complexity with dataand people, was related to lower risk of dementia. The relative risk for thoseworking with complex data (analysing, synthesising, coordinating, etc) was
0.6 (95%CI 0.4 to 0.8) and working with people (mentoring, negotiating,supervising, etc) was 0.6 (95%CI 0.4 to 1.0). In persons with lower education,highest levels of work complexity involving analysis and self-direction,
could modify their dementia risk (RR 0.5, 95%CI 0.3 to 1.0). [65] Level II-2, good
However in another population-based study (10 years duration), the positiveeffect of work complexity were noted in those with vascular dementia only among
subjects who had high complexity of work with people (HR 0.4, 95%CI 0.2 to 0.9)
and high complexity of work with things (HR 0.5, 95%CI 0.3 to1.0).[66] Level II-2, good17

Evidence from a systematic review showed that higher brain reserve wasassociated with a lowered risk for incident dementia by 46% (OR 0.5,
95%CI 0.5 to 0.6) wherein brain reserve is a composite of education,
occupation, premorbid IQ and mental activities. Similarly, history ofhigh occupational status was associated with decreased risk of 44%(OR 0.6, 95%CI 0.5 to 0.7, p<0.0001) compared to low occupational
status. Protective effects of mentally stimulating leisure activities wereindependent of age, health, education and occupation (combined OR 0.5,
95%CI 0.4 to 0.6, p<0.0001). [67] Level I, good
In a recent systematic review of seven RCTs (n=3,194), it was foundthat cognitive exercise may confer a protective effect, showing a relative
improvement of 1.2-2.6 points in the MMSE (95%CI 0.3 to 1.8). The study
concluded that cognitive exercise training in healthy older individuals may
produce protective effects on cognition. [68] Level I, poor
There is some evidence that low education level is a risk factor for dementia
and AD.

Recommendation
Mentally stimulating activities should be continuously pursued throughout life.
(Grade C)
g. Social network
Social isolation and unengaged lifestyle have been reported to be associatedwith accelerated cognitive decline in ageing. The term social network is used tocapture the range of interactions, degree of engagement, marital status, support,
contacts and activities. There are no RCTs that have looked at the protective
effect of social networks on dementia. [69] Level III, fair
Compared to consistently high social engagement, low social engagement
in both midlife and l a t e l i f e r e s u l t i n i n c r e a s e d r i s k o f d e m e n t i a(HR 1.7, 95%CI 0.9 to 2.9), while men whose social engagement
decreased from midlife to late life had a significantly higher risk of dementia(HR 1.9, 95%CI 1.1 to 3.1). [70] Level II-2, fair
There is insufficient evidence on the role of social engagement in reducing therisk of dementia.
18

2.2.3

Medicationa. Non-steroidal anti-inflammatory drugs
The role of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk ofdementia arise from the inflammatory hypothesis of AD. Fifty percent ofretrospective studies found that NSAIDs is protective against dementia andcognitive impairment and 20% of prospective studies found an association withincident dementia but not with cognitive decline.
However it was concluded that further research is needed to establish
dose, drug and duration of potential benefits with careful consideration ofpotential risks. [13] Level II-2, good
The Alzheimers Disease Anti-inflammatory Prevention Trial (ADAPT) researchgroup performed a placebo controlled RCT comparing the use of naproxen (220mg bd) or celecoxib (200 mg bd) against placebo in the development of incident
dementia. The study was carried out on volunteers (≥ 70 years) with a family
history of AD (n=2528). Events while on treatment versus placebo yielded HR of
2.0 (95%CI 0.8 to 5.0, p=0.14) for celecoxib and 2.4 (95%CI 1.0 to 5.8, p=0.06)
for naproxen. The study did not support the hypothesis that celecoxib or naproxen
prevents AD, at least within the early years after initiation of treatment. [71] Level I, fair
In another study, Szekely et al did an analysis of pooled data from six
prospective cohort studies. They found that the risk of AD was reduced
among those who reported use of any NSAIDs (HR 0.8, 95%CI 0.6 to 0.9;
adjusted HR 0.8, 95%CI 0.7 to 0.9). [72] Level II-2, poor
A retrospective case control study that compared veterans over the age of 55
who developed dementia (n=49,349) against a matched control group(n=196,850), found that compared with no NSAID use, the adjusted OR for AD
among NSAID users decreased from 1.0 for ≤1 year of use (95%CI 0.9 to 1.0)
to 0.8 for >5 years of use (95%CI 0.7 to 0.9). Ibuprofen was the only NSAID thatwas found to reduce the risk of AD (OR decreased from 1.0 (95% CI 1.0 to 1.1)
to 0.6 (95% CI 0.4 to 0.8)). Effects of other NSAID classes and individual NSAIDs
were inconsistent. It was concluded that long-term NSAIDS (ibuprofen) use wasprotective against AD.[73] Level II-3, fair

Recommendation
Long-term usage of Non-Steroidal Anti-Inflammatory Drugs should not be
used as a measure to prevent dementia as risks outweigh benefits. (Grade B)
19

b. Statins
Evidence from biological and epidemiological studies suggests that high levelsof serum cholesterol may promote the pathological process that leads to AD.
These findings raise the possibility that treating patients with cholesterol lowering
agents might reduce the risk of developing AD.
Zhou et al, performed a meta-analysis on seven prospective and nested
case-control studies (n=13,920) and showed that pooled RR of case-control
studies was 0.3 (95%CI 0.2 to 0.5) while pooled RR for cohort studies
was 1.2 (95%CI 0.9 to 1.5). When the two placebo controlled RCTs werepooled, the mean difference using ADAS-cog score was 1.8, which was not
significant.[74] Level II-2, good
A prospective cohort study (n=1146) after adjusting for age, gender, education,
and APOE 4 allele found that the use of statins was associated with less cognitive
decline (p=0.0177). Similarly using logistic regression model on incidence of
dementia showed that the use of statins may be associated with reduction inincident dementia (OR =0.3, p=0.067). [75] Level II-2, fair
Two prospective cohort studies analyzed the association of statins use
and neuropathological changes in brain tissue after death. The firstcohort (n=110) of cognitively normal subjects followed up for 12 years
demonstrated that statins had significantly reduced risk for typical AD
neuropathology.[76] Level II-2, good However, a recent study (n=929) did not
find any association between statins and the risk of developing AD.
(HR=0.9, 95%CI 0.5 to 1.5). [77] Level II-2, good
A recent Cochrane systematic review of two placebo controlled RCTs
(n=26,340) found that statins given later in life to individuals at risk ofvascular disease have no effect in preventing AD or dementia. [78] Level I, good

Recommendation
Statins are not recommended for the primary prevention of dementia or
Alzheimers disease. (Grade A)

20

c. Antioxidants
One of the mechanisms causing neuronal degeneration is free radicals. Many
studies have found evidence of increased level of oxidative damage to neurons
and mitochondrial DNA in AD and MCI. Vitamin E functions biologically as ascavenger of different free radicals by working as an anti-oxidant.
There is a dearth of large scale prospective RCTs on the role of Vitamin C (ascorbicacid) and Vitamin E in the prevention of dementia. Vitamin E at higher doses
increased all cause mortality, and as such Vitamin E should not be recommended
for the primary or secondary prevention of AD or other dementias. [13] Level I, good
A cochrane review found only two RCTs on the use of Vitamin E, of which only
one was on prevention (n=516), involving MCI patients on vitamin E (1000 IU bd).
It showed no significant difference in the progression from MCI to AD (HR 1.0,
95%CI 0.7 to 1.4, p= 0.91). This systematic review concluded that there was noevidence of efficacy of Vitamin E in the prevention AD. [79], Level I, good

Recommendation
Antioxidants are not recommended for the primary prevention of dementia or
Alzheimers disease. (Grade A)21

3.0 EARLY IDENTIFICATION OF DEMENTIA
The development of dementia pathology occurred many years before thesymptoms became obvious. Of interest is the transitional stage of cognitive
impairment between normal aging and early AD, the state of mild cognitive
impairment (MCI).
The concept of MCI evolved when early detection and identification of individuals
at the pre-clinical stages of dementia became increasingly important in recent
years. The diagnostic criteria for MCI subsume the presence of subjective memory
complaints, preferably corroborated by a close informant, and documented by
an abnormal performance on cognitive tests, adjusted for age and education.[80]These deficits must have no, or minimal, impact on global intellectual functioning
and on the ability to perform ADL. The patient should not have evidence of
dementia.[81] The MCI classification was recently expanded to encompass othercognitive domains, such as executive functioning and language, allowing thediagnosis of single and multiple-domain amnestic or non-amnestic MCI.
A meta-analysis showed that patients with MCI convert to dementia at rates ofapproximately 10% per year. [82] Level I,good A single-domain amnestic MCI may be
a pre-dementia stage of AD whereas multiple-domain MCI may be a precursor
to both AD and VaD. Single domain non-amnestic MCI may be found in the
prodromal phases of FTD, VaD, DLB, or even depressive disorders.[83]There were no studies that discussed the benefits of early identification ofdementia. The NICE guideline states that, there is some evidence that earlyrecognition and active therapy at the point of sharp decline in cognitive function
delays the subsequent need for nursing home care and reduces the risk of
misdiagnosis and inappropriate management.[13], Level I, good)

22

4.0

ASSESSMENT AND DIAGNOSISAssessment is an integral component of managing people with dementia. At theearliest opportunity, assessment may be done to screen people who are at riskof having dementia. Assessment tools are available for screening and diagnostic
purposes as well as to determine the severity of dementia. Consequently
assessment tools look at the level of cognitive and psychosocial impairment.

4.1

ASSESSMENT AT PRIMARY CARE

Primary care physicians are the gatekeepers to specialised services. The elderly
are frequent users of primary care facilities. Despite this, majority of patientswith dementia remain undetected and therefore do not receive the appropriate
treatment. [84],[85]4.1.1

Routine cognitive screening

More than 60% of patients made their first contact for treatment at the moderateor severe stage of illness, [86] ,[84] corresponding to 9-11 years after the onsetof the first symptoms. [87] The growing number of at-risk elderly population andthe availability of treatment options favour early screening in order to optimize
the benefit of early treatment. However there is insufficient evidence to support
routine screening of elderly people for dementia at primary care level. [13] Level I,
good;[88] Level I, good

A cross-sectional study (n=3340) found that physicians identified only 18.7%of all patients with dementia. False positive rate for those screened positive wassubstantial and acceptance rate was poor as only 52% who screened positive
agreed to go into the diagnostic assessment phase. The program was not effective
in detecting dementia and due to high refusal rates, many cases would be missed aswell. [89] Level III, good
In two longitudinal studies on subjective memory complaints (SMC) it was found that
there was a higher association of SMC with incident dementia (OR= 2.2, 95%CI 1.2
to 4.0, p=0.008) in a cohort followed up for an average of 2.4 years. Despite this,it has a low predictive power of 14.1% (negative predictive value (NPV) of 81.6%).
[90] Level II-2, fair
There was a higher number of AD pathology amongst those with higher
memory complaints (amyloid plaques, p=0.01 and tau tangles, p<0.001), which
could not be explained by depression and other medical illness near to death.[91]Level II-2, good
Another cross-sectional study found that among subjects with subjective
memory complaints, depression need to be ruled out first. However delayedrecall, if present, was a sensitive predictor of future cognitive decline.[92] Level III, fair23

Questions to ask patients with subjective memory complaints
Modified from Jessen et al, 2007 [92] level III ,fair
1. Do you feel like your memory is becoming worse?
Possible answers are: ‘NO’ OR ‘YES’
2. Proceed to ask questions on the Subjective Memory Decline Scale[93](a) Do you have trouble remembering things that have happened to you
recently?
(b) Are you worse at remembering where belongings are kept?
(c) Do you have trouble recalling conversations a few days later? AND(d) Do you have more trouble remembering appointments and social
gatherings?
The choices of answers are the following: (1) NO (2) YES
Any ‘YES’ answer will require further assessment.
Source : Modified from Jessen et al, 2007, [91] level III ,fair

Recommendation
Routine screening in the primary care for dementia amongst the older population
is not recommended. (Grade A)

Screening among those with subjective memory complaints is
recommended. (Grade B)
Practitioners should have a high index of suspicion for dementia when patient
has subjective memory complaints. (Grade C)

4.1.2

Screening instruments for people at risk of dementia

There are many types of tools found suitable for screening of patients at risk ofdementia. The Mini Mental State Examination (MMSE) has been recommended
due to its widespread acceptance and use. In addition, the Newcastle Mental Test
Score, 7-minute Screen, General Practitioner Assessment of Cognition (GPCOG)
and 6-items Cognitive Assessment Test has also been suggested. [13] Level I good
As most clinicians have limited time, there are other brief screening tools that are
more practical to be used at primary care settings. A systematic review analysedand compared 22 instruments by their likelihood ratio (LR). Below is the list ofbrief instruments (Table 2) suggested according to the brevity of tests: [94] Level II-2 good24

Table 2: Brief Screening Tests at Primary CareNo

Instruments

LR Positive

LR negative

1

7-Minute Screen

47

0.1

2

Memory Impairment Screen

33

0.2

3

Brief Alzheimer Screen

25

0.0

4

Mini-Cog

13

0.3

5

Abbreviated Mental Test

6 =12

0.4 =0.6

6

Short and Sweet Screening Instrument

11

0.1

7

Clock Drawing Test (CDT)

1.2 =7.7

0.1 =0.786-items Screener

7.3

0.2

9

Short Cognitive Evaluation Battery

10 Subjective Memory Complaints (SMC)

6.3

0.1

6.5 (informants)
1.8 (patient)

0.1 (informants)
0.4 (patient)

11 General Practitioner Assessment of Cognition (GPCOG)

4.8

0.2

12 3-Words Recall

4.3

0.4

A systematic review looked into patient-administered and informant-rated
instruments. It was concluded that two instruments from the 16 reviewed,
satisfied the criteria of good screening tools based on their psychometric andadministration properties. The Concord Informant Dementia Scale (CIDS) andInformant Questionnaire on Cognitive Decline in Elderly (IQCODE) were brief andyet still retained reasonable accuracy.[95] Level II-2, good
An informant-rated instrument involves the administration of the various aspectsof memory and intellectual function in everyday situation when compared to earlier
in life.[96] A meta-analysis of 10 studies concluded that informant tests were aseffective as brief cognitive tests at screening for dementia.[97] Informant-rated
instruments such as the IQCODE, had also been found to be a better screening
tool in large populations with varying degree of educational background. [98]Combining an informant-rated instrument and cognitive testing increased theaccuracy of prediction of dementia caseness compared to either tests usedalone. [99] Level III, good;[100] Level III, good
In 2007, the Family Health Development Division of the Ministry of Healthembarked on the cognitive screening programme at the primary care centers.
A combination of informant-rated instruments such as Symptoms of Dementia
Screener (SDS), and patient administered instrument, such as, the Elderly
Cognitive Assessment Questionnaire (ECAQ), MMSE and 4-item GeriatricDepression Scale (GDS-4) were used.
25

The Symptoms of Dementia Screener (SDS) is a caregiver based tool. The resultsfrom a cross sectional study (n=103) using SDS showed that the Area under
the curve (AUC)=0.9, with a standard error of 0.0 (95%CI 0.8 to 1.0). A cut
off score ≥ 5, gave a sensitivity (Sn) 90.2%, specificity (Sp) 84.6%, positive
predictive value (PPV) 85.9% and negative predictive value (NPV) 84.6%. Thiswas compared against the MMSE cut off 23/24. For MMSE, Sn was 78.7%, Sp
92.2%, PPV 94.1% and NPV 75%. [101] Level III, good
The ECAQ is specifically designed to assess cognition among the elderly
population in developing countries, taking into account the cultural difference andthe relatively low literacy rate. This 10-items questionnaire had a Sn of 85.3%,
Sp of 91.5% and PPV of 82.8%. Both the inter-rater and the test-retest reliability
were good at 0.8 and 0.9 respectively.[102]The short version of geriatric depression scale (GDS) had been found to be as effective
as the long scales in screening for depression in the older people. A cross sectional
study comparing the four items against the 15 items and 30 items, found that GDS-4
did not differ from the longer scales in terms of accuracy. [103] Level III (Refer to Table 3)

Table 3: Accuracy of different versions of GDS
Test
GDS-4

Sn

Sp

PLR

NLR

AUC-ROC

82%

67%

2.5

0.3

0.8 (0.7 to 0.9)

GDS-15

82%

60%

2.1

0.3

0.8 (0.7 to 0.9)

GDS-30

100%

62%

2.7

0.0

0.9 (0.8 to 0.9)

Recommendation
A caregiver based questionnaire (e.g. Symptoms of Dementia Screener) is to be
used before proceeding with a more detailed screening. (Grade C)
Appropriate tools that can be used for detailed screening include MMSE orECAQ and GDS-4 to be used. (Grade C)

4.1.3

Referral of patients with dementia to specialist services(secondary/tertiary)

Patients with dementia may require referral to specialist services (memory clinics
where available) after initial management at primary care level. Two guidelines
recommended that while most cases of dementia can be diagnosed and managed
by primary care clinicians, some cases may require referral to specialist services fordiagnosis, management and special care [104], Level III, fair;[105] Level III, fair (Refer to Table 4)26

Table 4: Summary of reasons for referral to specialist care services are:1

Issue of diagnosis, including for second opinion2

Difficult behaviour problems

3

Psychiatric co-morbidity e.g. depression

4

Treatment issues, including accessibility to certain drugs

5

To obtain community support services

6

Age is less than 60 years old

7

Rapid deterioration in clinical condition

8

Possible industrial exposure to heavy metal

9

Genetic counselling10

To involve other health care professionals in management

a = Australia Practice Guidelines 2003

a,b

a

b

b = Royal College of Psychiatrist 2005

In the local context, due to the lack of expertise and human resource at the
primary care level, all patients suspected of dementia, should be referred to thesecondary/tertiary services or memory clinics.

Recommendation
All patients with suspected dementia should be referred to a geriatric
psychiatrist, psychiatrist, geriatrician or wherever available a memory clinic, fora more comprehensive assessment. (Grade C)

4.2

MEMORY CLINIC

According to a United Kingdom National Audit Office report (2007), two-thirdsof patients with dementia in England receive no formal diagnosis or have nocontact with specialist services at any time during their illness. Furthermore,some hospital services avoid dementia diagnoses because of concerns about
their capability and resources, and fears that the diagnosis might delay a patient’s
discharge.[106]27In its five-year National Dementia Strategy (NDS), the Dept of Health UK
endorsed the creation of a network of memory clinics throughout their country,
staffed by a multidisciplinary team. This enables referrals from GPs to clinicalspecialists based in memory clinics. The aim is to improve dementia care andearly diagnosis.[107] Level III, good)
Memory clinics have become acceptable and useful vehicles for improving
the identification, investigation, and treatment of memory disorders, including
dementia. They are provided in various settings; the setting determining clientele
and practice. All aim to facilitate referral from GPs, other specialists, or by self
referral, in the early stages of impairment, and to avoid the stigma associatedwith psychiatric services.[108] Level III, good NICE Guideline recommends memory clinics
for service provision with a multi-disciplinary approach from old age psychiatrists,
nurses, allied health staff and social workers. [13] Level I, goodIn keeping with this, the European Dementia Consensus Network also
recommends provision of memory clinics with an emphasis on multidisciplinary
collaborative care for both early, accurate diagnosis and management. Here,close collaboration between GPs and specialised memory clinics may be theideal model. [109] Level III, fair
Besides hospital-based or centralised memory clinics, an alternative model for
memory clinic is a primary care-based practice with specialist input, for greater
outreach and greater acceptability. [110] Level III
A cohort study (n=290) of consecutive referrals demonstrated that specificservices for early dementia increased the identification of people with early
dementia and provision of adequate care. Those receiving such services appear
to improve in terms of quality of life and BPSD. Furthermore such memory
services can be incorporated within the local services. Acceptability is also
greater when it is seen as a memory services rather than services defined under
old age psychiatry or mental health. [111] Level II-2, good28

Multidisciplinary team consists of:Core team members
v Clinicians - Geriatric psychiatrist/geriatrician/neurologist
v Medical Officers
v Psychologist
v Nurses/Psychiatric nurses
v Occupational therapist
v Physiotherapist
Supportive members
v Primary care physicianv Home care nurses/community nurses
v Dietician/Nutritionist
v Social worker
v Speech therapist
v Pharmacistv Alzheimers Society representative
Recommendation
Memory clinic with a multidisciplinary team should be set up at secondary andtertiary care level. (Grade C)

4.3

ASSESSMENT OF DEMENTIA AT THE SECONDARY/TERTIARYCARE LEVEL

A more comprehensive clinical evaluation of all the three domains of cognition,
behaviour and function will be required in those suspected of dementia, with theaims of making an early diagnosis, assessing complications and determining thecauses of dementia.
It is important to exclude delirium (acute confusional state), especially when
the presentation is acute in onset. If the onset of symptoms is subacute(weeks to months), then the exclusion of obstructive sleep apnea (OSA),
depression and other neurological conditions, need to be made as most ofthese conditions are treatable.
29

4.3.1

History Taking

The basis of any clinical evaluation is in getting a detailed history, which should
encompass the mode of onset of symptoms, course of progression, patternof cognitive impairment and the presence and pattern of the non-cognitive
symptoms. History from a reliable informant is mandatory. [63] Level I, good
Practical questions to assist in the diagnosis using the DSM-IV criteria(refer to Appendix 5).

4.3.2

Physical examination

Physical examination, particularly neurological examination is essential in the
differential diagnosis of dementia.

4.3.3

Brief cognitive tests

Mental state examination would encompass assessment of cognitive function
which can be made by using brief cognitive instruments, or a more detailed
neuropsychological assessments administered by a clinician or neuropsychologist.
There are many brief cognitive tests that can be used to obtain an objective
measure of the cognitive impairment.
Neither the NICE-SCIE guideline, SIGN and Swedish Health Technology
Assessment make any specific recommendations as to which cognitive
tests to be used. The tests listed below are simple and easy to use at
the clinic setting, with fair to good evidence. The Singapore Guidelines
recommend some instruments that had been validated for its population(e.g. ECAQ, Abbreviated Mental Test, Chinese MMSE and Vascular
Dementia Battery Test).

It is well to remember that a diagnosis of dementia can only approach a highlevel of accuracy if the clinician follows up the patient for many years and/or
compares multiple assessment instruments. [112]30a. Mini Mental State Examination (MMSE) (Folstein)
The most commonly used cognitive test is the MMSE. The MMSE score andcut-off values are affected by several factors including educational levels, age,and ethnic differences. Certain component of the MMSE may be more reliable inpointing towards the diagnosis, rather than the total score.
The cut-off value for MMSE had to be adjusted according to the educationlevels of the subject. A cut-off scores of 27 gave Sn 0.9, Sp 0.9, PPV 0.8,
NPV 0.9 and a cut-off of 28 (Sn 0.78, Sp 0.8, PPV 0.6, NPV 0.9) in the higher
educated subjects yielded a better diagnostic accuracy, in both the cognitively
intact and cognitively impaired subjects among the Caucasians and English
speaking subjects. [113] Level III, fair
The AUC values for the MMSE ranged from 0.9 to 1.0, indicating excellent
overall accuracy at identifying dementia across age and education stratifications.
The lowest AUC value (0.8) occurred in the group aged 97 and older with theleast education. The highest AUC value (1.0) was for group aged 90 to 93 withvocational school or some college education. However when using MMSE in
the 90 and older age groups, age and education related adjustments should beconsidered. [114] Level III, good
The differences in MMSE were most pronounced among the non-educatedand lower educated subjects, with the MMSE showing a lower Sp (62.8%)
and a lower LR (2.6) among the Malays. A cut-off value of 23/24 among thebetter educated yielded AUC-ROC at 94.8%, Sn of 97.5%, Sp of 75.6%, anda LR of 4.0. [115] Level III, good
A recent cross sectional study to validate the Malay version of MMSE (M-MMSE)
was done on 300 subjects (24.3% with dementia vs 75.5% controls) using
3 versions: M-MMSE-7(serial 7), M-MMSE-3 (serial 3) and M-MMSE-S (spell‘dunia’ backwards). It was found that the optimal cut-off scores varied with eachversion and education level. Gender adjusted cut-off scores should be appliedin those with lower education. The validity of the M-MMSE for the 3 versions arelisted below (Table 5).[116] Level III, good31

Table 5: Cut off values & accuracy of the different versions of the Malay MMSE
M-MMSE-7(n=300)

M-MMSE-3(n=160)

M-MMSE-S(n=145)

Optimal cut-off

21/22

18/19

17/18

Sensitivity

88.5

97.1

97.7

Specificity

75.3

90.0

93.3

PPV

53.7

57.6

62.5

NPV

95.5

99.2

100.0

AUC

0.9

1.0

1.0

Details of the Malay Mini Mental are available in Appendix 3.

MMSE has been compared with other cognitive screening instruments suchas Clock Drawing Tests (95%CI 0.64, 0.6 to 0.7) [117] Level III, fair, Verbal Fluency(65-66%) and Blessed Dementia scale (67-72%), and were found to be wellcorrelated. [118] Level II-2, fairb. Verbal Fluency (VF)There are two types of verbal fluencies-categorical (semantic) verbal fluency (e.g:categories of fruits, vegetables, animals) and phonemic (letter) verbal fluency,
involving letters starting with F, A, and/or S.
A meta-analysis showed that patients with AD showed more impairment
in categorical (semantic) fluency irrespective of the MMSE scores(r=0.7, p<0.001). [119] Level I, good
It had also been shown that verbal fluency was sensitive to early memory changes,
but had to be used with other non-fluency measures.[120] Level III, fair The test was
associated with specific psychological functions at different stages of cognitive
impairment as suggested by the different cognitive predictors of Categorical
Verbal Fluency Test (CVFT) scores in the healthy and the questionable dementia
or mild cognitive impairment group. [121] Level III, good32

Verbal fluency could be influenced by education, and so the cut-off scores
had to be adjusted according to the educational levels (0 years: 9 (Sn 90.5%
and Sp 80.6%); 1-3 years: 12 (Sn 95.2% and Sp 80.0%); 4-7 years: 12(Sn 91.3% and Sp 91.9%) and ≥ 8 years: 13 (Sn 82.6% and Sp 100.0%).
[122], Level III, goodIt was not influenced by repeated learning in patients (n=69)
with MCI or dementia. [123] Level III, poor
Categorical (Semantic) fluency test may assist in the early detection of dementia.
The LR indicated that a score of <15 is 20 times more likely to occur in an
individual with AD as opposed to a person without AD.[124] Level III, fairc. Category naming
A meta-analysis of 21 studies (n=1066) on subjects with AD and controls showedthat patients with AD, were better at naming living things if it is presented in colour(significant difference between monochrome (1.5, 95%CI 1.9 to1.3) and colour (2.6,
95%CI 4.1 to 1.7). However the studies showed some heterogeneity (Qwi=36.1,
p=0.007). There were also gender differences seen, with female patients having
more problems in naming living things compared to non-living things (for living
things only the proportion of males approached significance (p=0.06) and for
non-living things, the proportion of males were significant (p=0.03)) [125] Level I, faird. Clock Drawing Test
The clock drawing test was found to be a reliable screening instrument for
dementia but was influenced by age, gender and education. [126] Level III, good In theolder person with less than four years of education, it was certainly not a valid
screening test for dementia. [127] Level III, good
The Clock Drawing Test can be done by drawing to command (CLOX I) or drawing
to copy (CLOX II). Both showed a high AUC-Receiver Operating Characteristic(ROC) at 84% and 85% respectively.[126] Level III, good
There are many types of scoring systems available of which, the best was thethree-factor system, using quantitative and qualitative scoring (e.g. Sunderlandscoring). It showed a high inter-rater correlation and classification agreementof 0.9-1.0 for AD, but a weak correlation with mild dementia (kappas of 0.2 to0.4). [128] Level III, good) Another study however, did not find any differences among thedifferent scoring systems. [127] Level III, good33

Clock Drawing Test that required time setting showed a high Sn (81% to93%) and low Sp (49% to 60%). Misdiagnosis was low as shown by theOverall Misclassification Rate (OMR) of 0.2 to 0.3. [129] Levels III, good Clock Drawing
Test also had a fairly good accuracy in discriminating between FTD from AD
and normal subjects, correctly identifying 88.9% of FTD and 76% of AD
patients with an overall prediction accuracy of 83.6%.[130] Level III, good A goodalternative was the Clock Reading Test as both Clock Reading Test and Clock
Drawing Test showed significantly good correlation of r=0.5. [131] Level III, faire. Montreal Cognitive Assessment (Nasreddin)
The Montreal Cognitive Assessment (MoCA) is a simple and brief screening
instrument better at identifying MCI (Sn 90%, Sp 87%) and early AD (Sn 100%;
Sp 87%) compared to the MMSE [MCI (Sn 18%) and AD (Sn 78%)] [132] Level II-2, good.
MoCA was also sensitive in detecting mild cognitive impairment in patients with
Parkinson Disease. [133] Level III, fair
The usual cut-off scale for MCI was 26/27, among the Western population with atleast 12 years of education. It had to be validated to the culture and educational
background of the subjects, as seen in the Korean version which predicted abetter accuracy at a lower cut-off (22/23; the Sn of 89% and 98% to MCI and AD
respectively, with a good Sp of 84%). [134] Level III; good
This instrument can be downloaded from w w w. m o c a t e s t . c o m .

f. Clinical Dementia Rating Scale (Morris)
The Clinical Dementia Rating (CDR) can be used for the detection of
MCI and mild dementia as shown by the poor performance on the othercognitive neuropsychological assessments. Use of CDR was influenced bysubject’s educational level, 57% concordance rate in those with less than
two years of education. [135] Level III, fair The CDR-Sum of Boxes (CDR-SOB)
may be a better indicator of questionable dementia rather than the CDR
global scores. [136] Levels III, poor
4.3.4.

Neuropsychological test

Cases presenting with subtle cognitive deficits will require a morecomprehensive assessment, using specific neuropsychological test batteries,
beyond the capabilities of the clinician. A series of tests administered bya clinical psychologist will require at least two to three hours of testing,covering the aspect of intelligence and memory, assessment of psychomotor
speed, information processing, attention and concentration, and the higher
executive function.
34

Neuropsychological tests are also useful in determining the subtypes of dementia
such as AD, FTD, DLB and VaD. It can also help in differentiating these dementia
subtypes from depression, when the features are not very clear cut.

Recommendation
History, physical and neurological examination remains an importantcomponent of assessment of dementia. (Grade C)
At the secondary/tertiary level, the brief cognitive tests that can be used
include the MMSE, categorical verbal fluency (CVFT), category naming, Clock
Drawing Test (CLOX-I or CLOX-II) or Clock Reading Test and Montreal Cognitive
Assessment. (Grade C)
When the diagnosis of dementia is inconclusive, then neuropsychologicaltests will be required. (Grade C)
All tests need to be validated for the culture, language and educational levelof the population. (Grade C)

4.3.5

Assessment of Behaviour and Psychological Symptomsof Dementia

Behavioural changes are present in most individuals with dementia, becoming
increasingly common as dementia progresses.[137] Behaviour and PsychologicalSymptoms of Dementia (BPSD) or neuropsychiatric symptoms, such as
depression, anxiety, agitation, paranoia, hallucinations and sleep problems, areseen in up to 90% of AD patients in the Asian countries, similar to that in theWestern countries. [138];[139];[140] Aggression and agitation which occur in 30% to
50% of patients with dementia,[141] is of great concern because it is a major
antecedent to institutionalisation,[142] increases costs and caregiver burden,
and leads to an overall poor prognosis.[143];[144] Hence BPSD should clearly be
documented and assessed in PWD.
These behavioural problems can be rated objectively using behaviour scales
which may be either self-rated, caregiver-based or observer reports. Some of thescales that can be used include the Neuropsychiatric Inventory (NPI) [145], Brief
Psychiatric Rating Scales (BPRS) [146] or Behavioural Pathology in AD Rating Scale(BEHAVE-AD).[147]35

Both the NICE and the SIGN guideline suggested that all PWD should be assessedfor depression, in view of its high prevalence. These guidelines did not makeany recommendations on the instruments to be used for the assessment ofdepression in dementia. [13] Level I, good;[63] Level I, good) However, the Singapore guideline
suggested that the Geriatric Depression Scale (GDS)[148] and the Cornell Scalefor Depression in Dementia (CSDD) [149] could be used but did not mention the
diagnostic accuracy of these instruments. [45], Level III, goodIt was found that both the Montgomery-Asberg Depression Rating Scale (MADRS)[150]
with a ROC-AUC of 0.9 and the CSDD (ROC-AUC of 0.7), performed wellin distinguishing depressed from the non-depressed patients with early onset
dementia (p<0.044). However MADRS had a strong correlation with CSDD
(rs=0.8, p<0.001), and the NPI subscales of dysphoria (rs=0.7, p<0.001) andapathy (rs=0.6, p<0.001). [151] Level III, fair
People with dementia may not exhibit the typical features of depression as
outlined in DSM-IV criteria. The National Institute of Mental Health Depressionin Dementia criteria (NIMH-dAD) (Sn 94%, Sp of 85%, PPV 77% and NPV 96%)
was able to identify patients with dementia who were depressed better than thecriteria for DSM-IV Major Depression (14%, p<0.001) or the DSM-IV criteria for
Major or Minor depression (36%, p=0.021) and as well as CSDD (30%, p=0.004)
and the GDS (33%, p=0.0041) at the established cut-off points. [152] Level II-3, good

Recommendation
Behaviour problems in people with dementia should be enquired on a routine
basis and rated qualitatively where possible. Suggested scales include NPI,BPRS and BEHAVE-AD. (Grade C)
All patients with dementia need to be assessed for depression. (Grade A)
The National Institute of Mental Health Depression in Dementia criteria(NIMH-dAD) can be used to make a diagnosis of depression in people withdementia. (Grade B)
The diagnosis and severity of depression in dementia can also be determinedusing qualitative scales such as the Geriatric Depression Scale OR Cornell
Scale for Depression in Dementia. (Grade C)36

4.3.6

Assessment of Functional Impairment

Functional impairment can be assessed based on the activities of daily living(ADL). Basic activities of daily living (BADL), relates to the day-to-day core survival
abilities, while instrumental ADL (IADL), defined by their higher level of complexity,
reflects the ability to live independently in the community. Difficulties in performing
ADL are progressive in AD and the related dementias, involving IADL to a greater
extent than BADL. [153] There are many scales available to assess ADL which canbe rated subjectively by the patient or objectively by the caregiver or observer.
The different dementia subtypes may differ in terms of their ADL. Patientswith AD may have less impairment in their ADL compared to those with FTD
or DLB. Those in the latter groups did not only differ in distinctive profiles offunctional impairment, but also in the specific types of activities.[154];[155]Persons with MCI showed slower speed of task performance and clinicallysignificant functional impairments, particularly on informant-based measure. [156]In a systematic review of five studies using four types of ADL scales: Index of
ADL [157]; IADL Scale [158] Modified Blessed Dementia Scale [159] and Functional
Activities Questionnaire [160] the sensitivities and specificities obtained when used
for population screening were shown below (see Table 6). However there may besome bias in the result, in view of the heterogeneity of the studies in terms of ageof the subjects and different literacy levels. There was also no adjustment done
for gender. [161] Level I, fair

Table 6: Sensitivity and specificity - Activities of Daily Living (ADL) scales
1
2
3
4
5
6
7
8

Principal author
Juva
Juva
Juva
Barberger-Gateau
Bermejo
BelandBelandGarcı´aTotal 8Functional scale
DS (Blessed)
IADL
FAQ
IADL
FAQ
IADL
FAQ
IADL

N
391
426
370
2763
3936
430
430
3214

Sn (95% CI)
84.0 (80.0–87.3)
91.0 (87.9–93.4)
94.0 (91.1–96.0)
94.0 (93.1–94.8)
90.8 (89.9–91.7)
92.1 (89.2–94.3)
98.4 (96.7–99.2))
85.0 (83.7–86.2)

Sp (95% CI)
82.0 (77.9–85.5)
86.0 (82.4–89.0)
84.0 (79.2–87.4)
71.0 (69.3–72.7)
90.6 (89.7–91.5)
91.5 (88.5–93.8)
89.0 (85.7–91.6)
66.0 (64.3–67.6)

11,960Recommendation
All people with dementia will need to be assessed on their activities, both inbasic activities of daily living and instrumental activities on a routine basis.
(Grade C)
37

4.4

DIAGNOSTIC CLASSIFICATION

Ascertain that the patient meets the clinical criteria of dementia, as definedby either the International Classification of Diseases-10 (ICD-10) or the
Diagnostic Statistical Manual (DSM-IV (1994) or DSM-IV-TR (2000)). Mostof the available criteria are based on the presence of clinically significant
cognitive change over time. [162]History remained essential in diagnosing dementia. Among the criteria of
dementia, DSM-IV have the highest agreement with history (k=0.8) compared to
DSM-III-R and history, (k=0.8).[163] Level II-2, fair
The final step in the clinical evaluation is to determine the dementia aetiology
or subtype, as this will determine the management and treatment, including thedecision on starting specific drug therapies. According to the two systematic
reviews. [13] Level I, good ;[164] Level I, good the DSM-IV-TR and ICD-10 definitions of dementia
are often appropriate in AD where memory is always affected but not always
appropriate for VaD, FTD or DLB where memory is not predominantly impaired.
The NICE guidelines listed the diagnostic criteria for each specific dementia
subtypes.
The AD criteria mentioned in the Singapore Guidelines include the DSM-IV
criteria [165] and the National Institute of Neurologic, Communicative Disorders
and Stroke–AD and Related Disorders Association Work Group (NINCDS-ADRDA)
criteria for AD [166] The National Institute of Neurological Disorders and StrokeAssociation Internationale pour la Recherche et l’Enseignement en Neurosciences(NINCDS-AIREN),[167] Alzheimer Disease Diagnostic and Treatment Centre (ADDTC)
criteria for VaD[168] and the Hachinski Ischemic Score (HIS) [169] and Modified
HIS [170] can be used for VaD. Table 7 summarises the different criteria for thedementia subtypes. Details of ICD-10 and DSM-IV-TR are available in Appendix
4 and 5 respectively.

4.4.1

Diagnostic criteria for dementia subtypesa. Alzheimer Disease
The clinical diagnosis for AD can be made using the clinical DSM criteria or the
NINCDS criteria. The latter criteria were mainly used in research. For probable AD,
both DSM-III-R and NINCDS-ADRDA have reasonable Sn (81%) and Sp (70%).
For possible AD, the NINCDS-ADRDA criteria had a higher sensitivity but a much
lower specificity (48%). [13] Level I, good
38

The specificity and sensitivity of the clinical diagnosis of AD against theneuropathological diagnosis was 75.9% and 60.6% respectively.
Neuropathological investigations remained critical to determining dementia
diagnosis.[171], Level II-2, poor
In an analysis of three epidemologic studies (n=175) comparing the clinicaland neuropathologic diagnoses, it was found that the sensitivity of a clinicaldiagnosis of probable or possible AD was 93%, with an overall diagnostic
agreement of 81%.[112] Level II-2, good.

b. Vascular Dementia
For VaD, DSM-IV and NINCDS-AIREN showed poor validity and inter-rater
reliability. The sensitivity with all criteria tend to be low (50%), but the specificity
was good (85%). [13] Level I, good The Alzheimer Disease Diagnostic and Treatment
Centre (ADDTC) criteria for VaD and the criteria for Vascular Cognitive Impairment(VCI) showed better sensitivity (88%) and specificity (75%), against post
mortem confirmed diagnosis, if used by an experienced rater. [172], Level II-2, fairc. Lewy Body Disease (DLB and PDD)
The consensus criteria for DLB had low sensitivity but highspecificity. [13] Level I , good In a recent study, it was found that there was agood correlation between clinically probable DLB using the 3 rd Consortium
Dementia of Lewy Bodies criteria and the pathological criteria (>95%), on
52 patients with DLB. [173] Level II-2, fair
Dementia with Lewy Body (DLB) and PDD are separated by the duration ofParkinsonian features which has to be present for more than a year before theonset of dementia for PDD, and less than a year for DLB.[13] Level I, goodd. Frontotemporal Dementia
For the diagnosis of FTD, the current consensus criteria lacked sensitivity (36.5%)
for FTD if based on neuropsychological profile alone (specificity was 100%, PPV
100% and NPV 64%), but when used with MRI, the sensitivity (63.5%) improved(Sp 70.4%, PPV 65.6%, NPV 68.5%). The used of SPECT/PET improved sensitivity
further to 90.5% (Sp 74.8%, PPV 76% and NPV 89.8%). [174] Level III, fair
The presence of the 5 core diagnostic criteria (Lund-Manchester criteria) for
FTD had a sensitivity (79%), specificity (90%) with moderate positive LR (8.1)
but good negative LR (0.2). [175] Level II-2, fair39

e. Mixed Dementia
None of the diagnostic criteria currently available deals with mixed causes ofdementia. Until further evidence emerges, it is pragmatic to consider the condition
that it fits best. [13] Level I, goodf. Mild Cognitive Impairment
There was no mention of any criteria for MCI in both the systematic
reviews. [13];[63] The definition of MCI varies according to the tests used for casedefinition. [176] Level III; fair) The predictive accuracy of MCI, using the Petersen’scriteria, against AD was good only for amnestic MCI in older subjects(AUC for > 80 years = 0.8 versus AUC for aged 55-69 = 0.7). [177] Level III, good
Table 7: Diagnostic criteria for subtypes of dementia
Alzheimer
Disease [13]ICD-10

Vascular
Dementia[13]ICD-10 [178](Refer Appendix 4)

DSM-IV-TR [165](Refer Appendix 6)

Lewy Body Disease Frontotemporal(DLB and PDD)
Dementia[13]The third consensus
criteria for Dementia
with Lewy bodies [20]Lund Manchester
Criteria [179]
The NINDS
Workgroup on
Frontotemporal
Dementia andPick’s Disease[181]DSM-IV-TR[180]NINCDS-ADRDA [141] NINDS-AIREN[167]
Modified Hachinski
Ischaemic Score(MHIS) [169],[170]
The California
Alzheimers Disease
Diagnostic andTreatment Centers(ADDTC) (criteria for
Ischaemic VaD[168]40Recommendation
The diagnosis of the subtypes of dementia should be determined using thespecified diagnostic criteria. (Grade B)
The DSM-IV, ICD-10 and the NINCDS-ADRDA criteria should be used todiagnose Alzheimers disease. (Grade A)
The diagnosis for Vascular dementia and Vascular Cognitive Impairment (VCI)
remains difficult. The Hachinski Ischemic Score may be useful in the diagnosis
in the clinical setting. (Grade B)
The DSM-IV and the NINCDS-AIREN criteria may be used in the diagnosis ofvascular dementia in research setting. (Grade B)
The Lund-Manchester Criteria should be considered when frontotemporaldementia is suspected. (Grade B)
The Third Consortium Dementia for Lewy Bodies criteria should be consideredwhen making a diagnosis for DLB. (Grade B)
The Petersen’s criteria may be considered when making the diagnosis ofamnesic (Mild Cognitive Impairment) in older patients. (Grade C)
The diagnostic definition is still unclear for Mixed dementia and other types ofMild Cognitive Impairment.

4.5

Progression and severity of dementia

As dementia is a progressive disease, staging tools can be used as surrogate
markers of severity. The multiple domains involved in dementia mean that, there
are a variety of tools available that can assess the global severity, cognitive andfunctional impairment of the PWD. These tools would require information from an
informant. It may also be useful in monitoring the response of the patients to thedrug therapy.
Instruments that were often used include the MMSE, Global Deterioration Scale(GDS)[182], CDR, Functional Assessment Staging (FAST)[183] and others.
The CDR discriminates well with the MMSE (see Table 8) in all stages of dementia
severity as shown by the Cohen’s kappa ranging from moderate to severe: (0.4) for
MMSE 30 /CDR 0 (no dementia); (0.5) for MMSE 25-21/CDR 1 (moderate dementia);(0.7) for MMSE 20-11/CDR 2 (moderately severe); (0.7) for MMSE 10-0/CDR 3(severe)); except in cases of questionable dementia, where the kappa was fair
(0.2 to 0.3). [184] Level III, fair41

Table 8: Severity of cognitive impairment based on MMSE
Mild

MMSE 21 to 26

Moderate

MMSE 15 to 20

Moderately severe

MMSE 10 to 14

SevereMMSE 0 to 9

The CDR has good convergent validity against clinical features(87% agreement, k=0.8 for all dementias), psychometric tests, and evenbetter than DSM-III-R (agreement 85%, k = 0.8 for all dementias at all stages)
and at discriminating milder stages of dementia (agreement 82%, k=0.8).
It is less susceptible to educational, linguistic and social-cultural influences(r= 0.1, p=0,204) or age (r= 0.0, p=0.47). [185] Level II-2, fair CDR and the DSM-III-R
diagnosis showed a good agreement for most stages of severity (k=0.8), except
for questionable or mild dementia (DSM-III-R, k=0.2), where CDR was better,
especially in a multi-ethnic, low educated population. [186] Level III, fair
CDR is also shown to be highly correlated to the global deterioration
scale (GDS), in rating the severity of dementia (r 0.9), in both AD and VaDgroup. [187] Level II-2, good
In questionable dementia or MCI, a combination of clinical assessment onfunction, and episodic memory tests, particularly verbal and visual measures canpredict the progression to AD.[188] Level II-2, fair

Recommendation
The Clinical Dementia Rating Scale and Global Deterioration Scale may be
used as both are equally sensitive in mild cognitive impairment and early
dementia. (Grade C)
When a definite diagnosis of dementia has been established, any of the scales
suggested (MMSE, Global Deterioration Scale, CDR, Functional Assessment
Staging) for determining progression may be used. (Grade C)
42

4.6

Screening for co-morbid medical conditions

Screening for co-existing medical problems, should be a regular practice for all
clinicians, as co-morbid conditions are frequent occurrences among the elderly.
These co-morbid conditions can cause cognitive impairment or dementia that
may be treatable, such as hypothyroidism, vitamin B12 deficiencies, etc.
A basic dementia screen should be performed at the first assessment which
include:v

Routine haematology e.g. full blood count and erythrocyte
sedimentation ratev

Biochemistry tests (including electrolytes, calcium, glucose, and renal andliver function)v

Thyroid function testsv

Serum vitamin B12 and folate levels
NICE[13] Level III

The SIGN guidelines did not recommend any specific blood tests andindicated that these tests should be selected according to history andclinical circumstances. The Royal College of Psychiatrists in United Kingdom
recommended that thyroid function test as one of the tests to be performedin patients with suspected dementia.
Both systematic reviews,[13],[63] also concluded that routine screening for syphilis
was not indicated. The Singapore Guidelines stated that test for syphilis would be
best done when patients exhibited clinical features of neurosyphilis.

Recommendation
Routine blood tests should be performed in those suspected with dementia.
(Grade C)
Specific blood tests (e.g. test for syphilis) should be selected on clinicalgrounds according to history and clinical circumstances. (Grade C)
43

4.7

Neuroimaging

Although dementia is a clinical diagnosis, the use of neuroimaging is an importantpart of the evaluation of dementia. Neuroimaging encompasses both structuraland functional neuroimaging.

4.7.1

Structural neuroimaging

These would include modalities such as computed tomography (CT scan) andmagnetic resonance imaging (MRI) which can identify the non-neurodegenerativeand potentially treatable causes of dementia. Based on the recommendations by
the NICE guidelines and the SIGN, the role of structural imaging would be to ruleout any intra-cerebral pathology and aid in determining the dementia subtypes.
Serial MRI scanning could identify brain changes early before the clinical onset
of dementia. Although not diagnostic, serial scanning can assist in clinicaljudgement. [13] Level I, good ;[63] 2006, Level I, good
There have been some controversies with regards to whether structural
imaging should be done on all patients suspected of dementia. The
Singapore guidelines suggested using the criteria of the CanadianConsensus Conference on the Assessment of Dementia (CCCAD).
However, relying purely on clinical predictors for selection of patientsfor neuroimaging would result in a significant number of patients withreversible causes being missed. [13] ;[63];[189]Atrophy of the medial temporal lobe structures estimated by MRI/CT Brain helps
to differentiate AD from controls and AD from other dementia based on studies
that used clinical diagnosis as the gold standard. [47] Level I, good
Subtyping of dementia can be done by using CT/MRI based on visual rating,voxel based and volumetric MRI studies of specific anatomical areas. In a crosssectional study [190] Level III, good the white matter lesion load (WML) scores of the whole
cerebrum and the frontal lobe were significantly increased in VaD as compared tocognitively normal controls, MCI and AD (p<0.001) even after correcting for age
and cognitive performance.
Structural neuroimaging had added value in the routine clinicalassessment of cognitively impaired patients and is useful for the diagnosisof all neurodegenerative dementias or VaD, but mainly of non-AD cases(AD cases-Number Needed to Test =15.3, compared to non-AD, Number
Needed to Test = 4.1). However taking all dementia diagnoses into account,the use of neuroimaging yielded Number Needed to Test = 9.[191] Level III, good44

A combination of neuropsychological testing and neuroimaging could benefit
in the early detection of dementia and MCI. A four-year longitudinal study
on healthy subjects showed that when neuropsychological testing using
Weschler Memory Scale (WMS) was combined with the summed gray mattervolume on MRI, the specificity increased from 75% to 92%, and was able
to differentiate the presymptomatic MCI from the healthy group. Sensitivity
remained at 78%. [192] Level II-2, fair
Changes in the hippocampus and/or entorhinal cortex were able to differentiate
those with MCI who subsequently develop AD from those who did not progress.
Imaging measures of the hippocampus could help differentiate AD (including
early stage) from controls with < 6% overlap rates. [13] Level I, good
The Alzheimers Disease Neuroimaging Initiative (ADNI) is a longitudinal study
that looked into using the tensor based morphometry on serial MRIs on healthy
controls, MCI and AD patients. The AD group showed a significant and moregeneralised atrophy (rates vary from 2.1% to 2.4% in AD compared to 0.2% to0.7% in healthy controls). The MCI converters showed a more restricted atrophy
profile compared to the AD group.[193] Level II-2, good
Post-mortem studies have shown that thickness is reduced in regions of thecerebral cortex that are affected with AD.[194];[195] Methods have been developed
to measure cortical thickness on MRI. Initial studies of cortical thickness had
demonstrated that thinning in distributed association areas suggested that
regional atrophy can be detected across widespread cortical region. A study(n=64) found that AD patients had a thinner cortex (p < 0.001) in parts ofbilateral parietal and precuneus regions compared to FTD patients. In AD thecognitive impairment was negatively correlated with cortical thickening in thefrontal, parietal and temporal lobes, while similar correlations were not significant
in FTD. Measuring cortical thickness was found to be equivalent to the corticalvolume in differentiating between normal ageing, AD and FTD. [196] level III, poor
A longitudinal study (n=380) compared cortical thinning to brain amyloid imaging
among normal individuals and in those at different stages of dementia. The finding
showed that thinning in vulnerable cortical regions was related to symptom
severity even at the earliest stages of clinical symptoms. Subtle thinning was also
seen in asymptomatic older controls with brain amyloid binding as detected withamyloid imaging. [197] Level II-2, good45

In the local context, CT scan and high resolution and diffusion weighted MRI brain
is currently available, for clearer delineation of frontal and temporal lobe atrophy,
subcortical white matter changes as well as changes seen in Creutzfeld-Jakob
Disease (CJD). However expertise to quantify volumetric changes is severely lacking.

Recommendation
Structural neuroimaging such as CT scan of the brain and MRI should be done
where available in the evaluation of dementia to rule out intracranial pathology.
(Grade A)
MRI is the modality of choice to assist with early diagnosis and to detect
subcortical vascular changes. (Grade C)

4.7.2

Functional Imaging

Functional neuroimaging includes functional MRI, magnetic resonancespectroscopy (MRS), positron emission tomography (PET), single photon
emission computed tomography (SPECT) and many others. Specific ligands
such as the Pittsburgh Compound B (PIB) can be used with PET, as PET-amyloid
imaging markers. Use of such markers is currently limited to research setting.
Functional imaging is useful to help in the early detection of dementia, to predictchanges from MCI to incident dementia and also in the subtyping of dementia.

a. Single photon emission computed tomography (SPECT)SPECT can be used to differentiate AD, VaD & FTD if the diagnosis is in doubt.
SPECT imaging, iodine-123-radiolabelled 2β-carbomethoxy-3β-(4-iodophenyl)N-(3-fluoropropyl) nortropane (FP-CIT) SPECT would be useful if the diagnosis of
DLB and PDD is in doubt.
A systema tic revie w l o o k e d a t t h e a c c u r a c y o f b o t h p e r f u s i o nhexamethylpropyleneamine oxime (HMPAO) SPECT and 2(18F) fluoro-2-deoxy
D-glucose PET (FDG PET) showed a Sn of 77.1% and a Sp of 89% in separating
AD from normal controls, a Sn of 71% and Sp of 76% in separating AD from VaD,
and Sn of 71% and Sp of 78% in separating AD from FTD. On comparing theclinical criteria (with pathological confirmation) to SPECT, the clinical criteria for
AD, was more sensitive than SPECT (81% vs 74%). However, SPECT provided
higher specificity against other types of dementia better than the clinical criteria(91% vs 70%).[13] Level I, good46

b. Positron emission tomography (PET)
Fluoro-2-deoxy D-glucose (FDG-PET) had sensitivity and specificity of 90% and
70% respectively in pathological verification studies. It may have superiority over
SPECT in detecting AD. [13];[164] Level I, goodStandardized disease specific PET patterns could classify AD (95%), DLB (92%),
FTD (94%) and normals (94%). Posterior cingulate cortex and hippocampal
hypometabolism was seen in MCI. An AD PET pattern was seen in 79% of MCI
patients with deficits in multiple cognitive domains and 31% amnesic MCI. MCI
with non-memory deficits showed patterns ranging from absent hypometabolism
to FTD and DLB PET patterns. [198] Level III, good
In an eight-year cohort study of healthy elderly population using FDG-PET,
the baseline hippocampal glucose metabolic rates (MRglc) predicted decline
from normal to AD with 81% accuracy, from normal to other dementias with
77% accuracy, and from normal to MCI with 71% accuracy. Greater rates ofhippocampal and cortical glucose metabolic rates (MRglc) reductions were foundin those who were progressing to MCI or AD. [199] Level II-2, goodc. Neuroimaging biomarkers
PET imaging studies involving radioligands that bind directly to β-amyloid plaques,
such as the Pittsburgh Compound-B (PIB), a thioflavin derivative had been performed.
The binding of PIB to brain sections was highly correlated with total Aβ levels. [200] ;[201]A cross sectional study using 11-C PIB-PET, showed a correlation between
beta amyloid deposition with memory impairment and those diagnosed with
AD. Multiple linear regression analysis showed an increased PIB binding was
related to being diagnosed with AD (β: 0.6, p < 0.001). There was also a strong
inverse relationship between episodic memory and PIB binding in amnestic MCI(r -0.6, p<0.001). [202] Level II-2, fair
Another study (n=69), looked at 11 C-PIB PET binding in AD, normal aging andother dementias using visual analysis. The study found marked PIB corticalbinding in AD (neocortex and caudate nuclei) (p<0.05), but there was no corticalbinding of PIB (p<0.05) in FTD. In the MCI group, PIB binding clustered in AD
like pattern and was indistinguishable from AD subjects (p<0.05). In DLB, there
was an increased binding similar to AD but with a significant lower degree andvariable binding levels. [203], L evel III, poor

Recommendation
Functional imaging and neuroimaging markers are not recommended routinely
in the diagnosis of dementia. (Grade C)
47

4.8

Electroencephalogram

There was a limited role for the use of Electroencephalogram (EEG) in the
diagnosis of dementia. [13] Level I, good;[63] Level I, good There was limited evidence thateither visually rated EEG or qualitative EEG helped in the diagnostic workup todifferentiate AD patients from controls and other dementia disorders. [47] Level I, good
The use of EEG may be considered when there is a suspicion that there
is an underlying seizure disorder, Creutzfeldt-Jakob disease (CJD) or indelirium. 47] Level I, good EEG in sporadic CJD had a sensitivity of 65% andspecificity of 86%. [63] Level I, good

Recommendation
The use of EEG is only for selected cases where there is a suspicion of underlying
seizure disorder, Creutzfeldt-Jakob disease or delirium. (Grade A)

4.9

Biomarkers

Biomarkers are becoming increasingly important as possible early diagnostic
measures, as surrogate measures of the ongoing pathology, prognostic markers
for those at risk and to monitor drug therapy. [204] Biomarkers can be detectedfrom the brain (cerebrospinal fluid (CSF) or neuroimaging of amyloid receptors),
blood, or a combination.
Of the central nervous system biomarkers, CSF β-amyloid1-42, β-amyloid1-40, totaltau, and hyperphosphorylated tau (p-tau) have emerged as the major biomarkers
of interest. In patients with AD, there were a reduced levels of CSF β-amyloid andincreased levels of CSF tau.[205]4.9.1

CSF biomarkers

Three CSF biomarkers (Aβ, tau and ptau) were highly sensitive and specificat differentiating AD from normal ageing (Sn 92%, Sp 89%), depression
and certain forms of dementia, but showed a much lower specificity at
differentiating other dementias such as FTD, DLB and VaD. There wasevidence that the presence of 14-3-3 protein in CSF is a predictor forsporadic CJD, with reported sensitivities and specificities of above
90%. [13] Level I , good;[63] 2006, Level I , good48

Using neuropathological diagnosis of AD as the gold standard, it was shown thatneuritic plaques (NPs) was the only significant predictor of low Aβ 42 levels (OR
7.2 to 53.3) and high CSF-tau (OR 9.0 to 85.1). The best documentation for
Braak staging of AD was the ratio of ptau/Aβ 42 with a sensitivity of 91.6% andspecificity of 85.8%, making it useful as a biomarker. [206] Level II-2, poor
The tau/Aβ 42 ratio was a better at predicting MCI and mild AD compared tothe ptau/Aβ42 ratio (AUC tau/Aβ 42=0.8 vs AUC ptau/AβB42=0.7). Patientswith mild AD exhibited the same CSF biomarkers phenotype as the moreadvanced AD. [207] Level II-2, fair
In a longitudinal study, it was found that the levels of CSF Aβ 42 and tau
increased over time with comparable changes in all diagnostic groups, butthere was no evidence that biomarkers were sensitive as markers of diseaseprogression. [208] Level II-2, fair
The Alzheimer Disease Neuroimaging Initiative (ADNI) study on CSF biomarkers
compared ADNI cohorts against an autopsy cohort of CSF samples which had a
Receiver Operating Characteristic ROC-AUC 0.9 and sensitivity for AD detectionof 96.4%. The CSF biomarker signature of AD defined by Aβ 1-42 and t-tau in an
autopsy confirmed AD cohort, was also found in the ADNI cohort over the periodof 12 months. It detected mild AD and predicted conversion of MCI to dementia.
[209] Level II-2, good

In a cross sectional study comparing CSF biomarkers and cognitive profiles ofpatients with AD, the levels of Aβ42, tau and ptau in the CSF were found to affectthe severity of dementia as shown by impairment of memory, mental speed andexecutive functions in patients with AD. [210] Level III, fair
CSF tau/Aβ42 may be useful in discriminating between frontotemporal lobar
degeneration (FTLD) and AD (Sn 78.9%, Sp 96.6%) in autopsied patients. FTLD
presented with a different profile from AD.[211] Level III, poor The ptau/Aβ42 ratios
showed the best sensitivity of 77.2% and specificity of 80.7% at differentiating
FTLD from AD.[212] Level II-2, fair
Combining CSF biomarkers with neuropsychological testing did not improve
discrimination between AD and FTLD. However the number of subjects in thisstudy is too small to make any definite conclusion. [211] Level III, poor
49

When combined with amyloid imaging, levels of CSF Aβ42, augmented clinicalmethods of identifying individuals with amyloid changes. CSF tau/Aβ 42 ratio
showed strong promise as preclinical biomarkers that predict dementia in
cognitively normal adults. [207], Level II-2, fair
There may be other potential CSF biomarkers such as CSF serphins, Visinin Like
protein-1 (VLP-1) and cytokines. The study on the latter was excluded because of poor
quality. However a cross sectional study of CSF serphins and 1-antichymotrypsin may
facilitate the diagnostic classification of AD (Sn 96.5% and Sp 77.8%) but it cannot
improve the differentiation between AD and DLB. [213] Level III, good The neuronal injury
markers, VLP-1, showed good correlation with ptau in AD patients (r=0.9) compared
to control (r=0.6) and may have potential as a biomarkers in AD in future. [214] Level III, fair

4.9.2.

Plasma biomarkers

a. Aβ biomarkers
Individuals with elevated plasma Aβ42 were at increased risk of AD (OR 2.8, 95%CI
1.6 to 5.1). It was shown that plasma Aβ40 and Aβ42 but not the Aβ42/Aβ40 ratio, weremodestly related to age among those who remained non demented over a period of time
(Aβ40 = r 0.2, p <0.001; Aβ42= r 0.2, p <0.001; and Aβ 42/Aβ 40 ratio= 0.1,
p <0.037). Therefore, Aβ42/Aβ40 ratio did not appear robust to be useful as abiomarker of AD. [215] Level II-2, good
In a 10-year cohort study (n= 593), the ratio of plasma Aβ42/Aβ40 showed
evidence of association with conversion to MCI or AD (RR 3.1, 95%CI 1.1 to8.3) . The rates of conversion were: 5% at 4 years (95%CI 3% to 8%); 11%
at 6 years (95%CI 7% to 14%); 18% at 8 years (95%CI 12% to 24%) and
30% at 10 years.[216] Level II-2, fairb. Genetic markers and plasma lipoproteinsIn the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) (n=5804) it
was found that subjects with APOE ε4 was associated with a more rapid cognitive
decline, as measured by memory. There was a 2.5 fold difference incident
dementia in the APOE ε4+ group. The APOE ε4+ group had higher plasma totalcholesterol (p<0.001), higher LDL-C (p< 0.001), lower HDL-C (p<0.001), andhigher plasma triglyceride (p<0.001) levels than the APOE ε4- group. However
the influence of lipid levels on cognitive decline was less convincing. [217] Level II-2, fair50

Apolipoprotein E (APOE) was not only a risk factor for AD, but it may also be arisk factor for DLB. Those with APOE ε4 allele and high cholesterol level had afour fold increase to develop AD among heterozygotes and 16 fold increased
for homozygotes. APOE ε4 alelle also showed influence on DLB regardlessof whether the cholesterol level was high or normal. [218] Level II-2, good) PDD whencarefully defined was clearly not associated with APOE polymorphisms or with adistinctive plasma cholesterol profile. [219] Level II-2, fair

Recommendation
CSF biomarkers and plasma markers are not recommended in diagnosing mild
cognitive impairment or dementia. (Grade C)
CSF biomarkers are not recommended in determining progression of mild
cognitive impairment to dementia. (Grade C)
The use of genetic marker, APOE with or without plasma lipid, is notrecommended to be used on a routine basis, and is only to be used in clinical
trials. (Grade C)

51

5.0

PHARMACOLOGICAL INTERVENTIONS

Drugs should be used synergistically with psychosocial interventions
to improve cognition, function, and behaviour. The cognitive enhancers include
acetylcholinesterase inhibitors (AChEI) and N-methyl-D-aspartate (NMDA)
receptor antagonist. Other agents considered include ginkgo, vitamin E,
omega-3 fatty acid, folic acid, vitamin B and huperzine A.
Behavioural and psychological symptoms of dementia (BPSD), a common
presentation in PWD can be controlled with antipsychotics, antidepressantsand mood stabilisers.
Only specialists in the care of dementia (psychiatrists, neurologists,and physicians specialising in the care of the elderly) should initiate
treatment. [220] Level I, goodOnce treatment is initiated, patients should be regularly reviewed every 6months. Assessment of cognition, global functioning and behaviour should bedone regularly. Caregivers’ view of the condition at baseline and at follow-up
should be sought. [220] Level I, good

Recommendation
Only specialists in the care dementia (psychiatrists, neurologists, andgeriatricians) should initiate treatment. (Grade C)
Caregivers should be involved in the management of patient from the
beginning. (Grade C)

5.1

Cognitive enhancers

Cognitive enhancers involve two separate mechanisms of action. AChEI works byaugmenting the levels of acetylcholine in the brain to compensate for the lossesof cholinergic function. Another mechanism of action is via continuous stimulationof NMDA receptors by glutamate which triggers a cascade of biochemical events
that damage and kill surrounding neurones. [221]Acetylcholinesterase Inhibitors (AChEI) are currently recommended for mild tomoderate dementia (see the classification of severity in section 4.5). However,
only donepezil has been approved for severe dementia. Memantine an NMDA
receptor antagonist is approved for moderately severe to severe dementia.
52

This section on cognitive enhancers is adapted from the NICE technology
appraisal 2006. Although AChEI is recommended only to people with AD of
mild to moderate severity, healthcare professionals should not rely on MMSE
scores in deciding treatment initiation. [220] Level I, good

5.1.1

Alzheimer Diseasea. Mild to Moderate Alzheimer disease
Donepezil
Donepezil was found to be beneficial but of modest clinical significance in treating
cognitive decline in patients with AD based on 13 published RCTs, two systematic
reviews and an unpublished RCT. [220] Level I, good
Donepezil 10 mg (Weighted mean difference WMD = 3.01, 95%CI −3.9 to−2.1) was found to be more efficacious than donepezil 5 mg (WMD= -5.5,
95%CI -3.3 to−1.8) was better compared to placebo in terms of change
from baseline on Alzheimer disease Assessment Scale-Cognition (ADAS-Cog).
Using MMSE score, the change from baseline was better for donepezil 10 mg(WMD of 1.3, 95%, CI 0.8 to 1.8) compared to placebo.[220] Level I, good
In another RCT, donepezil improved the MMSE score on average of 0.8 point
when compared to placebo (95% CI 0.5 to 1.2, p < 0.0001).[220] Level I, good
Donepezil had fewer adverse events (mainly nausea, vomiting, diarrhea) whencompared with rivastigmine based on a large RCT (n=998). [222] Level I, good

Rivastigmine
Evidence from three systematic reviews, four published RCTs (n=1940) and two
unpublished RCTs (n=1380) suggested that rivastigmine was beneficial in AD at
higher doses (6–12 mg/day). [220] Level I, good
A meta-analysis of two RCTs (26 weeks duration) was associated with a significant
difference (MWD=-3.1, 95%CI,-3.8 to –2.4) for rivastigmine 6–12 mg/day whencompared with placebo using the ADAS-cog. [220] Level I, good
The Investigation of transdermal Exelon in Alzheimers disease (IDEAL)study (n=1195)
found that rivastigmine patch, 17.4 mg (20cm2/24 hours) and 9.5 mg (10 cm2/24
hours) showed similar efficacy to capsule (6 mg bd). However the target dose was
not achieved in most of the patients and the effective comparison dose was 9 mg/
day (capsule). In this study, all rivastigmine groups compared to placebo showedstatistically significant benefit at week 24 on ADAS-cog, only on the intention to treat last observation carried forward (ITT-LOCF) analysis (p < 0.05). [223] Level I, good
53

The 9.5 mg patch had approximately two thirds fewer reports on nausea (7.2%
versus 23.1%) and vomiting (6.2% versus 17%) compared to capsule. However
the 17.4 mg patch had similar tolerability to capsule. Local skin tolerability wasgood (>90% experiencing no, slight or mild skin irritation).[223] Level I, good

Galantamine
Based on a systematic review of seven published RCTs and one unpublished RCT(total n=4300), galantamine was found to be beneficial but of modest clinicalsignificance. [220] Level I, good
Galantamine (24 mg) when compared to placebo showed significant improvement in
ADAS-Cog change from baseline (MWD= -3.3, 95%CI –3.9 to -2.7).[220] Level I, good

Head to head comparison of AChEIIn two RCTs comparing donepezil with rivastigmine, there was no statisticallysignificant difference in terms of cognitive changes from baseline. There was no
published study comparing rivastigmine with galantamine. [220] Level I, goodA Cochrane systematic review found that all three AChEI were
efficacious for mild to moderate AD, with no significant differences
between them. [222] Level I , good

Memantine
A Cochrane review, based on three RCTs found that memantine(20 mg/day) showed small beneficial effect on clinical impression of change(CIBIC-Plus) (CIBIC-Plus 0.13 points change, 95% CI: 0.01, 0.25, p = 0.030),
and ADAS-Cog (0.99 points, 95%CI 0.2 to 1.8, p=0.01) for patients with mild
to moderate AD at 24 weeks. There was no significant difference in the numberof patients experiencing at least one adverse event (NNH=39). [224] Level I, good
In a RCT (n=403), memantine compared to placebo had been shown to beeffective in improving cognitive function in mild to moderate AD (-1.9 points,
95%CI, -3.1 to -0.6) on the ADAS-cog at week 24 endpoint. The Mixed Model
Repeated Measure analysis favoured memantine treatment at endpoint (-1.4
points, 95%CI -2.3 to -0.5, p=0.003). [225] Level I, good)
Memantine is registered to be used only in the treatment of moderately severe tosevere AD. However in patients who are unable to tolerate AchEI, memantine may
be considered as an alternative.
54

Recommendation
Acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) are
beneficial in improving cognitive function of people with mild to moderate
Alzheimers disease. (Grade A)
Patients on cognitive enhancers should be reviewed at least once every 6months by using psychometric measures (e.g. MMSE or similar, functional andbehaviouralmeasures). (Grade C)

b. Moderately Severe to Severe Alzheimer Disease
Donepezil
A Cochrane review showed that donepezil was effective in improving cognitive
function in moderate to severe AD treated for up to 52 weeks at a dose of 10 mg/
day (WMD=-2.9, CI 95%, -3.6 to -2.2) on ADAS-Cog. The benefits for patientson the 10 mg/day dose were only marginally larger than those on the 5 mg/day
dose. [222] 2006 Level I, good
Another RCT reported that patients treated with donepezil improved more on
the Severe Impairment Battery (SIB) (Least square [LS] mean difference= 5.5,
95%CI 1.5 to 9.8, p=0.008) and declined less on the Alzheimers Disease
Cooperative Study–Activities of Daily Living (ADCS-ADL) (LS= 1.7, 95%CI
0.2 to 3.2, p=0.03). There was also improvement in the MMSE scores frombaseline at 6 months after initiation of treatment when compared to controls(LS=1.4, 95%CI 0.4 to 24, p=0.009). [226] Level I, good
The incidence of adverse events was comparable between groups (donepezil
82% versus placebo 76%) with most being transient and mild or moderate inseverity. More patients discontinued treatment because of adverse events in thedonepezil group than in the placebo group. [226] Level I, good
Another placebo-controlled RCT had found that donepezil was superior
on SIB score change from baseline to endpoint (p< 0.0001). The results werealso in favour of donepezil in terms of CIBIC-Plus (p < 0.0473) and MMSE
(p< 0.0267). [227] Level I, good
The reported adverse events were consistent with known cholinergic effects ofdonepezil. The safety profile of donepezil in patients with severe AD was found tobe similar to those with mild to moderate AD. [227] Level I, good55

Rivastigmine
There was modest benefit for moderately severe AD (MMSE 10 to 14), in termsof ADAS-Cog scores (99%CI -7.5 to -2.6) based on the manufacturer’s
ITT-LOCF data from trials (n=232) of up to 24 weeks. However, there
was no evidence to support the use of rivastigmine in severe dementia(MMSE < 10). [220] Level I, good
Galantamine
For moderately severe AD, there were some modest benefits in terms of ADASCog scores (-6.1points, 99%CI -7.9 to -4.3) based on the manufacturer’s ITTLOCF data from trials (n=340) of up to 24 weeks. [220] Level I, good
The SERAD (Safety and Efficacy of Reminyl in Alzheimers disease) study foundthat galantamine could be used safely in elderly patients with severe AD. Althoughgalantamine improved cognitive function, it failed to significantly improve the coprimary parameter of overall activities of daily living. The mean total SIB score
improved by 1.9 points (95%CI –0.1 to 3.9) with galantamine, and worsenedby 3.0 points (95%CI –5.6 to –0.5) with placebo. The between-group meandifference was 4.4, (LS= 4.4, 95%CI 1.3 to 7.5, p=0.006). [228] Level I, good

Memantine
Memantine is effective in improving cognitive function of people with moderate
to severe AD. This conclusion was based on two systematic reviews, 13
published RCTs (n=4200) and one unpublished RCT. Two RCTs (n=650)
showed less deterioration of cognitive function following treatment withmemantine compared with placebo as measured by the SIB. The mean change
from baseline at end point LOCF analysis for memantine and placebo was–4.0 and –10.1 respectively (p < 0.001). There were however no statisticallysignificant differences on the CIBIC, MMSE and NPI. [220] Level I, good
In a Cochrane review, treatment with memantine (20 mg/day) in patients withmoderate to severe AD was found to have a small beneficial effect in two of threestudies of six-month duration. The beneficial effects were on cognition using SIB(2.9 points, 95%CI 1.7 to 4.3, p < 0.00001), ADL (ADCS-ADLsev) (1.3 points, 95%
CI 0.4 to 2.1, p=0.003), mood and behaviour (NPI)(2.8 points, 95%CI 0.9 to 4.6,
p=0.004), and CIBIC-Plus (0.28 points, 95%CI 0.2 to 0.4, p< 0.0001). [224] Level I, good
Another placebo-controlled trial (n=350) which used SIB as an outcome
measure found a significant effect at week 12 (p=0.019) and at week 18(p=0.048) on the LOCF analysis, but failed to show any statistically significant
benefit at week 24. [229] Level I, good56

Recommendation
Donepezil and memantine are modestly effective in improving cognitive function ofpeople with moderate to severe Alzheimers disease. (Grade A)
Galantamine may offered as an alternative in those with severe Alzheimers
disease. (Grade B)
Patients on cognitive enhancers should be reviewed at least once every 6months by using psychometric measures (e.g. MMSE or similar, functional andbehaviouralmeasures). (Grade C)

5.1.2.

Vascular dementia

There are well documented cholinergic deficits in VaD. [230] Ischaemia induces
excessive glutamate stimulation on NMDA receptors. This leads to excitotoxicity
and neuronal cell death.[230] Donepezil has been approved for VaD treatment in
New Zealand, India, Romania, South Korea and Thailand, while memantine has
been approved in Argentina, Brazil and Mexico.[231]a. Cognitive enhancers
Acetylcholinesterase Inhibitors(AChEIs) and memantine are currently
prescribed in dementia, other than AD, as part of a clinical trial or at clinicaldiscretion without licence. [13] Level I, good
Their efficacy and adverse effects in VaD had been reported in a recent metaanalysis of placebo-controlled RCTs (n=5183, duration 24-28 weeks), comprisingof three trials on donepezil, two on galantamine, one on rivastigmine and two on
memantine. [231] Level I, good There were significant cognitive effects for all drugs
using ADAS-Cog (-1.1 points, 95%CI, -2.2 to -0.1); for rivastigmine (12 mg
daily), (-1.6 points, 95%CI -2.4 to -0.8) for galantamine (24 mg), (-2.2 points,
95%CI -3.0 to -1.4) for donepezil (10 mg daily) and (95%CI -2.8 to -0.9)
for memantine (20 mg). On the Clinical Global Impressions scale (CGI scale), only
donepezil 5 mg daily had a positive effect (OR 1.5, 95%CI 1.1 to 2.1). Donepezil(10 mg) also showed a beneficial effect on the Alzheimer Disease Functional
Assessment and Change Scale (ADCS-CGIC) (-1.0 point, 95%CI, -1.7 to -0.2).
There were more dropouts and adverse events (mainly gastrointestinal symptoms
and insomnia) with the AChEIs, but not with memantine. [231] Level I, good57

In eight systematic reviews and RCTs,[230] Level I,fair donepezil (5 mg) was foundto be the most effective with a numbers needed to treat (NNT)=10, and numbers
needed to harm (NNH)=50 compared to other AChEIs. Galantamine (24 mg daily)
was also found to be effective (NNT=7) but less well tolerated (NNH=7). Rivastigmine
was not recommended due to insufficient evidence. Memantine (20 mg daily)
appeared to be safe and well tolerated but did not demonstrate effectivenessacross all cognitive outcomes and clinical global measures (NNT= 30). Therewas significantly less agitation with memantine treatment than with placebo(OR=0.5, 95%CI 0.31 to 1.0; NNT=30, 95%CI 15-337). [230] Level I, fair
In a placebo-controlled RCT of CADASIL patients (n=168, 18-week duration),
donepezil (10 mg) was found to have no treatment effect on the primary endpoint,
the Vascular-ADAS-cog. However, there was significant treatment effect favouring
donepezil on the following secondary outcomes involving executive function tests:
Trail Making Test (TMT) B Time (p= 0.023), TMT A Time (p= 0.015), and executive
interview-25 item (EXIT25) (p= 0.022). [12] Level I, good
Although the improvements were noted on several measures of executive function
and processing speed, the clinical relevance of these findings was not clear as
the improvements did not translate into a clinical meaningful benefit on IADL andon global dementia rating such as Disability Assessment for Dementia (DAD) and
CDR-SB. [12] Level I, good)

Recommendation
Acetylcholinesterase inhibitors may be prescribed in selected patients with
vascular dementia at the clinician’s discretion. (Grade A)

b. Drugs that control vascular risk factors
For people with VaD, there is currently no evidence to suggest that drugs that
control vascular risk factors such as anti-hypertensive, aspirin, statin andantidiabetic have any beneficial effect on cognitive symptoms. [232] Level I, good It is
assumed that the control of these comorbid conditions reduces the risk of further
cerebral damage, but there is no direct evidence that there will be any beneficial
effect on cognitive function. [13] Level I, good)
Recommendation
Patients with vascular dementia with concurrent vascular risk factors shouldbe treated with recommended drugs for the management of these problems.
(Grade C)58

5.1.3.

Lewy Body Diseases (Dementia with Lewy Body/Parkinson
Disease Dementia)

There is current interest in the overlap between PDD and DLB. Both conditions
have common presentations, involving similar brain areas, and both areassociated with deficits in both acetylcholine and dopamine. At present there
is no agent that slows down the progression of PDD.[13] Level I, good These groupsof degenerative dementias are associated with prominent BPSD, but the useof neuroleptics lead to two to three fold increase in mortality due to severe
neuroleptic sensitivity reactions. [233] Unfortunately, there had been too few
studies focusing on the use of AChEIs in the treatment of these conditions.
Rivastigmine is licensed for the symptomatic treatment of mild tomoderately severe dementia in patients with idiopathic Parkinson disease
and DLB.[13] Level I, good)
A large RCT of rivastigmine in PDD, showed improvement in primary andsecondary endpoints. However, the clinical significance of these benefits wereuncertain. It was likely that the modest improvements reflected heterogeneity of
response, with some patients responding far better than others.[13] Level I, goodA systematic review found that there was evidence from one RCT (n=541)
that rivastigmine had a moderate effect on cognition and to a lesser extent on
ADL in patients with PDD. The LOCF change score from baseline to week 24
significantly favoured rivastigmine: ADCS-CGIC, ((WMD=-0.50, 95% Cl -0.8 to-0.2, p=0.0004); MMSE (WMD=2.8, 95% Cl 0.3 to 1.7, p=0.003); ADAS-Cog(p=0.0002) and ADCS-ADL (WMD= 2.5, 95% Cl 0.4 to 4.6, p=0.02). [234] Level I, good
Clinically moderate or marked improvement on cognition and ADL wereobserved in 19.8% of the rivastigmine group and 14.5% of the placebo group(NNT=19); whereas clinical worsening was observed in 13.0% and 23.1%,
respectively. Overall, rivastigmine had moderate effect on cognition and to alesser extent on ADL.[234] Level I goodTolerability issues such as nausea and vomiting (NNH=11) appear significant
and will require careful management. More patients on rivastigmine compared toplacebo experienced nausea (NNH=6), vomiting (NNH=7), tremor (NNH=16) ordizziness (NNH=22).[234] Level I, good59

A Cochrane systematic review on DLB, found no statistically significant
difference between rivastigmine and placebo at 20 weeks (WMD=1.2,
95%CI, -0.6 to 3.0, p=0.19).[14] Level I, good

Recommendation
Rivastigmine may be considered in improving cognition in Lewy Body
Dementias. (Grade A)
Rivastigmine should be used cautiously in patients with Parkinson Disease
Dementia. (Grade A)

5.1.4

Frontotemporal Dementia (FTD)

The clinical and pathologic heterogeneity of frontotemporal lobar degeneration(FTLD) creates particular challenges for determining optimal pharmacologic
management. Unlike AD, cholinergic neurons are relatively preserved in FTD, andstudies using AChEIs have produced mixed results.
There had been reports that AChEIs frequently lead to more severe behavioural
impairments. [24];[174] A number of other medications that affect the function of specificneurotransmitter systems (example: SSRI on serotonergic neurons; memantine
on the aberrant glutamatergic neurotransmission) have been studied and may
offer modest benefits for the behaviouraland cognitive sequelae of this disorder.
[235]
There are no approved treatments available for any of the FTLD syndromes.

a. Acetylcholinesterase inhibitors
There had not been many trials of AChEIs in FTLD, as there was no rationale forusing medications that increase brain acetylcholine in patients with FTD. In a
study of FTD patients (n=24) who were treated with donepezil (10 mg, 6 months),
against those not treated, there was an increased of disinhibited or compulsive
acts on the FTD Inventory scores (p=0.05) in 30% of the subjects. There wasno change in the global cognitive performance or severity of dementia in thedonepezil group. Even though the number of subjects was small, the findings
indicated that AChEIs could worsen disinhibition and compulsions in patients with
FTD.[174] Level III, poor60An open label placebo-controlled RCT (18 weeks open-label and 8 weeks ofplacebo RCT) of galantamine (16–24 mg) did not find any significant differencesin the primary efficacy measures using the Clinical Global Impression of
Improvement (CGI-I) and Clinical Global Impression of Severity (CGI-S). There
was also no significant difference found on behaviour using the Frontal Battery
Inventory. The frequency of adverse events was more than 10%, but no significant
differences were observed in the two groups. [236] Level I, poor

b. Memantine
There is no placebo RCT available. A 26-week (n=37), open-label study ofmemantine (20 mg daily) showed that Semantic Dementia (SD) and FTD
patients had greater decline on the ADAS-Cog (SD subjects, p=0.001; FTD
subjects, (p=0.156). MMSE declined significantly (p=0.002) in the FTLD
combined. The overall change in CDR-SOB, was not significant (p=0.24).
Effects on behavior showed a transient improvement on NPI score, maximal
at week 16, but back to baseline by week 26. This was most prominent in the
FTD group. The overall estimate of change on the Frontal Battery instrument(FBI) at week 26 was 2.4±1.2 points (p=0.038). The most common side
effect was confusion.[24] Level III, fair
Recommendation
Acetycholinesterase inhibitors are not recommended for the treatment offrontotemporal dementia. (Grade A)
Memantine is not recommended for frontotemporal dementia. (Grade C)

5.1.5

Mild Cognitive Impairment

Mild Cognitive Impairment (MCI) is a heterogeneous clinical condition with several
subtypes and multiple aetiologies.[237];[83] There are still controversies on the useof cognitive enhancers in the treatment of MCI.

a. Galantamine
A Cochrane systematic review of two placebo controlled RCT (n=1903)
found no significant treatment effect on the ADAS-Cog at 12 months (WMD=-0.1, 95%CI -0.6 to 0.4) or 24 months (WMD=1.5, 95% CI, 0.9 to2.4). One of the trials reached significance in terms of conversion todementia (change of CDR score from 0.5 to ≥1.0) at 24 months. Combining
data from both trials, dementia conversion at 24 months was significant(OR 0.7, 95%CI 0.6 to 0.9) for galantamine (12-24 mg).[238] Level I, good61

A significantly higher death rate however was found in the galantaminegroup. Causes of death included bronchial carcinoma/sudden death, cerebrovasculardisorder/syncope, myocardial infarct and suicide. An interim study from the
manufacturer reported an adjusted HR of 3.0 (95%CI 1.3 to 7.3). This review
concluded that there was some marginal clinical benefit, but as yet unexplained
excess in death rate.[238] Level I, good
A consensus statement by the British Association for
Psychopharmacology reported that a significantly increased mortality
in two unpublished studies of galantamine have been observed and remain
to be explained.[239] Level III, goodb. Donepezil
A Cochrane review based on two RCTs (n=782), reported no evidence
to support the use of donepezil in MCI patients. This review concluded
that the putative benefits are minor and short lived. Those on donepezil
suffered significantly more side effects, mainly gastrointestinal and weredose related. [240] Level I, good
One of the RCTs demonstrated a modest treatment effect with donepezil (10 mg/day) compared with placebo at 24 weeks, on the ADAS-Cog (MD=1.9, 95%CI
0.5 to 3.3, p=0.007), using the ITT-LOCF analysis. There were no significant
treatment effects for donepezil compared with placebo for other measures ofcognitive function. In the second study, there was a significant difference in thedonepezil group (NNT=12, OR 0.4, 95%CI 0.2 to 0.7, p=0.003), after the firstyear of treatment. However this difference was not significant at the end of 3
years (OR 0.8, 95%CI 0.6 to 1.3, p=0.4).[240] Level I, good
In a more recent double-blind placebo controlled RCT (n=821) of MCI
with a three-week placebo run-in followed by 48 weeks of donapezil,
there was a small but significant decrease in modified ADAS-Cog
scores in favour of donepezil. Little change from baseline in CDR-SB
was observed in either group. Using the CGI of Change, the donepezil
treated group scored better only at week 6 (p=0.04). [241] Level I, goodAdverse events were generally mild or moderate. More donepezil
treated subjects (18.4%) discontinued treatment due to adverse events thanplacebo-treated subjects (8.3%). The most frequent adverse events leading
to discontinuation of donepezil were diarrhoea (16.4%), muscle spasm(13.3%) and nausea (9.7%).[241] Level I, good62

c. Rivastigmine
A placebo-controlled RCT (n=1018) concluded that there was no significant
benefit of rivastigmine on the progression rate to AD or on cognitive function overfour years. It was found that 17.3% of patients on rivastigmine and 21.4% on
placebo progressed to AD (HR = 0.8, 95%CI 0.6 to 1.1, p=0.225). There wasno significant difference between the rivastigmine and placebo groups on the
cognitive test battery.[223] Level I, fair
Similar adverse events were reported for rivastigmine (95.6%) and placebo(92.7%). The frequencies of nausea, vomiting, diarrhoea, and dizziness were
two to four times higher in the rivastigmine group. Most adverse events weremild or moderate in both groups. [223] Level I, fair

Recommendation
Acetylcholinesteras inhibitors are not recommended in people with mild
cognitive impairment. (Grade A)

5.2.

DRUGS TO CONTROL Behavioural AND PSYCHOLOGICALSYMPTOMS OF DEMENTIA (BPSD)

The management of BPSD is challenging. Concerns have been raised in identifying
which behaviours and which patients are most likely to improve. Although nonpharmacological interventions should be the first-line treatment, a wide variety ofpharmacological agents can be used synergistically in the management of BPSD.

5.2.1.

Treatment of Agitation, Aggression and Psychosisa. Antipsychotics
Antipsychotic drugs are the most frequently used ‘off-label’ forinstitutionalized patients with dementia. [242] In the US and Europe, up to
60% of people with dementia residing in care facilities are prescribedneuroleptics. [243], Level III, fair The US Food and Drug Administration has put
out black box warning about the risk of increased mortality and stroke
associated with antipsychotics. [244] Level III, fair
The NICE guideline found that there is insufficient evidence to support use of
atypical antipsychotics in treatment of psychosis, aggression and agitation inpatients with dementia.[13] Level I, good63

In a meta-analysis of 16 RCTs (n=5110) on effects of atypical antipsychotics(risperidone, quetiapine, olanzapine and aripiprazole) on agitation and aggression
in dementia, the NNT ranged from 5 to 14. Small statistical effect sizes on
symptom rating scales supported the evidence for the efficacy of aripiprazole,using the NPI-total (OR =1.5. 95%CI 1.1 to 2.0, p=0.005) and risperidone,using the BEHAVE-AD (OR= 1.8, 95%CI 1.4 to 2.3, p<0.0001). Meanwhile, theNNH ranged from 10 for somnolence to 100 for death. Approximately one-third
dropped out without overall differences between drug and placebo (OR =1.1,
95%CI 0.9 to 1.3, p=0.5). [332] level I,fairIn the Clinical Antipsychotic Trials of Intervention Effectiveness: Alzheimers
Disease (CATIE-AD) (n=421), atypical antipsychotics (olanzapine, quetiapine andrisperidone) when used for psychosis or agitation/aggression were no better thanplacebo for the primary outcome (time to discontinuation for any reason) or thesecondary outcome (CGI).The time to the discontinuation of treatment for any
reason was not significant (p=0.52) for olanzapine (median 8.1 weeks), quetiapine(median 5.3 weeks), risperidone (median 7.4 weeks) and placebo (median 8.0
weeks). The median time to the discontinuation of treatment due to a lack ofefficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) compared
to quetiapine (9.1 weeks) and placebo (9.0 weeks) (p = 0.002). However, the trial
utilised a population of patients with mild agitation or psychosis. [245] Level I, fair
In the last few years, two serious adverse events have been associated withatypical antipsychotics, that is, cardiovascular events and death. [246] In themeta-analysis by Schneider et al, the pooled rates of cardiovascular eventswere 1.9% in atypical antipsychotic group versus 0.9% in placebo group(OR= 2.1, 95% CI 1.2 to 3.8).[245] Level I, fair
The DART-AD Trial (n=165) concluded that withdrawal of neurolepticsin AD patients showed no overall detrimental effect on function and cognitive
status. There was no significant difference in SIB scores at baseline and at 6
months. The estimated mean difference in deterioration was favoring placebo(MD=-0.4, 95%CI -6.4 to 5.5, p=0.9). Similarly, there was no significant
difference between the placebo group and the continuing treatment group(MD=-2.4,95%CI -8.2 to 3.5, p=0.4) on the NPI.[247] Level I, fair64

Risperidone
In the treatment of non-cognitive functions in PWD, risperidone (mean 1
mg/day) showed improvement in neuropsychiatric symptoms as measured
by NPI total and BEHAVE-AD on the psychosis (p=0.01) and aggression(p=0.0002) subscales. [242] Level I, good
An observational study (n=132) showed that risperidone was significant(p<0.0001) in improving BEHAVE-AD scores at four and 12 weeks andon most of the NPI items (p<0.0001). Agitation improved significantly(p<0.0001) at endpoint. In addition, caregiver distress was reduced
significantly. [248] Level II-3 ,good
In patients with severe dementia (n=119) (MMSE 5-9), treatment with risperidone(mean 1 mg/day) showed better global improvement as measured on the CGI-C(p=0.024).[249] Level I, fair
Risperidone (all doses pooled) treated patients were significantly more likely
to have serious adverse cerebrovascular events (NNH=50), falls (NNH=8)
and extrapyramidal symptoms (NNH=11). [242] Level I, good
A meta-analysis (n=1721) showed that mortality associated with cardiac-related
adverse events was higher with risperidone than placebo during and within 30
days of treatment discontinuation (HR 3.0, 95%CI 0.9 to 0.6) (NNH=115). Foursubjects on risperidone died due to cerebrovascular events during or within 30
days of use (HR 2.7, 95%CI 0.3 to 24.0).[250] Level I, fair

Aripiprazole
Based on two RCTs (n=464), there was a moderate to high quality evidence
that aripiprazole (15 mg/day for 10 weeks) produced small benefits in termsof reduced neuropsychiatric symptoms as measured by the total score on the
NPI or BEHAVE-AD, in AD. [13] Level I, goodA Cochrane systematic review concluded that aripiprazole(2-15 mg) given for 10 weeks showed benefit compared to placebo, in the
BPRS-Psychosis (MD=-0.7, 95%CI -1.3 to -0.1, p=0.03). [242] Level I, good
In another RCT (n=473), aripiprazole (10 mg) compared to placebo showedsignificantly greater improvement in mean change on the NPI-NH psychosis
subscale (p=0.013 from week 6 onwards), Cohen-Mansfield Agitation Inventory(CMAI) (p=0.023) and BPRS total (p=0.030).[249] Level I, fair)65Adverse effects due to aripiprazole (2-15 mg) compared with placebo was mainly
somnolence (NNH=15).[242] The cerebrovascular adverse events reported weredose-dependent (p ≤ 0.03).[249] Level I, fair
While a study by Mintzer et al [249] showed improvement on the NPI-NH psychosis
subscale, another study (n=256) using the same scale (p=0.883) did not find any
improvement.[251] Level I, poor However, there were no long term studies on aripiprazole.

Quetiapine
The NICE Guideline concluded that quetiapine (50-100 mg/day)
can be used for the non-cognitive symptoms of dementia. [13] Level I, good
In a RCT (n=435) of 10 weeks duration, quetiapine (200 mg/day) improved
agitation. The difference was significant on the observation carried forward (OC)analysis (p=0.014) but not on the LOCF analysis (p=0.065). In the secondary
analysis, quetiapine showed significantly greater improvement on the CGI-C
score compared to the placebo group on both LOCF (p=0.017) and OC (p=0.002)
analyses.[252] Level I, poor
Neither quetiapine (100 mg) nor haloperidol (2.5 mg) (n=284) comparedto placebo was efficacious in the treatment of psychosis using themean total BPRS scores (p=0.217 versus placebo and p=0.354 versus
haloperidol). [253] Level I, poor
There was no difference in rates of adverse events (falls, hypotension,
sedation, extrapyramidal symptoms and cardiovascular adverse events
between quetiapine at doses of 100 mg/day and 200 mg/day, suggesting
an absence of dose-dependency for tolerability and safety. The RR for deathon quetiapine versus placebo was 2.1 (95%CI 0.6 to 7.2) and was not
significant.[252] Level I, poor

Olanzapine
A 24-month, open-label uncontrolled study (n=68) of olanzapine (mean dose 4
mg/day), supported the use of these medications in AD, VaD, FTD, DLB and PDD.
The FTD group, showed the best response as reflected by a decrease in NPIscore (p<0.01) and BEHAVE-AD score (p<0.05). In this group, the most common
adverse effect was somnolence (31%), which was reduced up to 12% when the
dosage was lowered. Maximal response was found among patients who presented
with symptoms of delusions, hallucinations, anxiety and agitation. Benefits
were also seen in the DLB group, reduced NPI score (p<0.01) and BEHAVEAD (p<0.01). PDD patients responded well to olanzapine as seen by decreasing
NPI and BEHAVE-AD scores (p<0.05) and (p<0.01) respectively. [254] Level II-3, fair66

General Principles of the use of antipsychotics in BPSD
Drugs may be appropriate in the following situations:a. Where drugs have a specific indication (e.g. depression or psychosis),regardless of the severity and frequency of symptoms
b. Where the problem symptom is severe and treatment is needed quickly
e.g. dangerous or distressing to the patient or othersc. Where behaviours have no clear situational trigger or occur in a setting
where carers cannot cope with serious behaviour problems
Drugs are inappropriate in these conditions: wandering, restlessness andagitated behaviours that do not represent a danger to the patient or others
In cases of unexpected harmful behaviours, prescription of medication on a prn(when necessary) basis is allowed. However, medication should be given not
more than twice in 7 days without an assessment of the cause and developmentof an appropriate care plan.
For those who require regular medication, the ‘3T’ approach is a goodpractice:• drug treatments should have a specific target symptom• the starting dose should be low and then titrated upwards and• drug treatments should be time limited
Atypical antipsychotics should be continued forv people who still have continuing BPSD
v where it is felt that severe adverse consequences may occur (orhave occurred) if they are discontinued, andv when no alternative treatment approaches are suitable.
Modified from Faculty of the Psychiatry of Old Age (2004) and the Omnibus
Budget Reconciliation Act (OBRA) guidelines[255]

Recommendation
Antipsychotics should not be used routinely to treat patients with dementia withaggression and psychosis. (Grade A)
If indicated, atypical antipsychotics should be considered. (Grade A)
The family needs to be informed of the adverse events prior to commencementof treatment. (Grade C)
Patient should be assessed regularly and antipsychotics should be tailed down
and withdrawn as early as possible, after resolution of symptoms. (Grade C)
Refer to Appendix 10 for drug dosages and adverse effects.

67

b. Cognitive enhancers
According to the NICE guideline, donepezil (10 mg/day) compared to placebo
reduced neuropsychiatric symptoms in patients with dementia. There wasmoderate quality evidence suggesting that rivastigmine (12 mg/day for 20 weeks)
may produce benefits in reducing psychotic symptoms in DLB patients. There
was insufficient evidence to determine whether memantine or galantamine
produce benefits in neuropsychiatric symptoms in people with VaD.[13] Level I, goodA RCT (n=262), the Cholinesterase Inhibitor and Atypical Neuroleptic in theManagement of Agitation in AD (CALM-AD) concluded that the donepezil(10 mg) given for 12 weeks duration was not superior to placebo in treatment
of severe agitation in patients with AD. In this study, patients had also
received four weeks of psychosocial intervention prior to commencement ofdrugs. The CMAI score from baseline to 12 weeks did not differ significantly
between the donepezil and placebo groups (MD= -0.1, 95%CI -4.4 to 4.2,
p=0.94). The proportion of patients responding to treatment was similar in
the two groups. The reduction in the NPI score also did not differ significantly
between the two groups (p=0.96).[256] Level I, fair
A pooled post hoc analysis of six RCTs (n=1826, moderate to severe dementia)
of 24/28 weeks duration, compared memantine (20 mg/day) to placebo. The
ITT-LOCF analysis found that memantine treated group showed symptom
improvement on the NPI total scores (p=0.008) at end-point. There wassignificant symptom improvement on delusions (p=0.045), agitation/
aggression (p=0.028) and irritability/lability (p=0.048). Patients who
were asymptomatic at baseline also showed significantly less emergenceof symptoms of agitation/aggression (p=0.002), irritability/labilty(p=0.004) and night-time behavior (p=0.050).[257] Level I, fair
A systematic meta-analysis of 5 placebo-controlled RCTs (n=1750) that
rated BPSD with the NPI found that patients on memantine improved by
1.99 points on the NPI scale (95%CI -0.1 to -3.9, p=0.041). However
the effect sizes were small and the studies were too heterogenous to beconclusive. [258] Level I, poor

Recommendation
Acetylcholinesterase inhibitors or memantine may be used for the treatmentof behavioural and psychological symptoms of dementia. (Grade B)
Rivastigmine may be used in the treatment of behavioural and psychologicalsymptoms of Lewy Body Dementia. (Grade A)
68

c. AntidepressantsIn a systematic review (24 studies) on FTD, two placebo controlled
RCTs using serotonergic agents were identified. The first RCT reported thattreatment with paroxetine (40 mg) (n=10) for six weeks did not improve
behavioural symptoms, and was associated with a worsening of cognition
compared to placebo. The second RCT (n=26), was a crossover study
that demonstrated a significant decrease in the NPI score with trazodone(up to 300 mg/day), but no effect was seen on the cognition (MMSE). In
the same paper, a total of six open label and uncontrolled studies foundthat the combined mean reduction based on NPI was15.4 points withantidepressant treatment. However these studies had small sample size,
most were not controlled and thus subject to placebo bias. There was
likely a publication bias toward positive trials. Only trazodone appeared tohave a significant effect on the behavioural symptoms of FTD.[259] Level I, fair
Recommendation
Antidepressant is not effective in the treatment of Behavioural andPsychological Symptoms of Dementia (BPSD) in Frontotemporal dementia.
(Grade B)
5.3

TREATMENT OF DEPRESSION AND MOOD SYMPTOMS

5.3.1

AntidepressantsBased on one systematic review which included Selective Serotonin Reuptake
Inhibitor (SSRIs) and Tricycyclic antidepressants (TCAs), antidepressantswere beneficial in reducing depressive episodes and improving generalfunctioning. [13] Level I, good
A meta-analysis of five placebo controlled RCTs which included SSRIs(fluoxetine, sertraline) and TCAs (clomipramine, imipramine) showed efficacy on
antidepressants in depressed AD patients (NNT=5). The NNH for dropout owing
to adverse events was not statistically significant (NNH=36). Only two studies
investigated the properties of the more commonly used SSRIs and no studies
investigated the properties of newer classes of antidepressants.[260] Level I, fair

Recommendation
Antidepressant (preferably Selective Serotonin Reuptake Inhibitor) can beused for the treatment of depression in dementia. (Grade A)
Refer to Appendix 11 for drug dosages and side effects

695.3.2

Mood stabilisers

The NICE Guidelines concluded that neither valproate nor carbamazepine wasrecommended for use in treatment of depression or anxiety due to the significant
risks that outweighed benefits. Their use is associated with more numbers ofadverse events compared to placebo. [13] Level I, good
A placebo controlled RCT (n=14) concluded that valproate was not effective
for the management of agitation in moderate to severe AD, and may be poorly
tolerated in this population. [261] Level I, poor

Recommendation
Mood stabilisers are not recommended for mood symptoms in dementia.
(Grade B)
5.4

COMBINATION THERAPYAs the two classes of drug (AChEI and NMDA antagonist) are believed to work on
different mechanisms, it seems reasonable that additive effects can be achieved
from combination therapy.
Hypofunction of other neuronal systems such as monoaminergic and serotonergic
systems in the brain of AD patients has also been reported. [262]

5.4.1

Combination of Acetylcholinesterase Inhibitor with memantine

In a placebo-controlled RCT (n=404), subjects with moderate to severe
dementia on donepezil therapy were randomised to receive memantine orplacebo. The result favoured the combination of donepezil with memantine
as seen in the small but significant effects on global function, (55% vs 45%
unchanged/improved on CIBIC), cognitive function (SIB 3.4 points), ADL and
BPSD (NPI 3.8 points). [13] Level I, good
In a prospective non-randomised trial (n=382) the combination of memantine
and AChEI slowed the cognitive (p<0.001) and functional decline (p<0.001) in
AD, compared to AChEI alone or no treatment. [263] Level II-2, poor
Another prospective non-randomised trial (n=202) in moderate to severe
dementia, showed that combining AChEI with memantine had beneficial effectin terms of cognitive function compared to monotherapy (77.9% versus 46.3%
respectively). [264] Level II-2, poor
70

5.4.2

Combining Acetylcholinesterase Inhibitor with Selective
Serotonin Reuptake Inhibitor (Serotonin Augmentation)

A RCT (n=122) did not show any superiority of adding serotonin stimulation
to rivastigmine in improving cognitive function using MMSE (p=0.002) and
Weschler Memory Scale III (p=0.00) compared to rivastigmine alone on the
MMSE (p=0.000) and WMS-III (p=0.000). [265] Level I, fair

5.4.3

Combining Acetylcholinesterase Inhibitor with multivitaminsupplementation

A placebo-controlled RCT (n=89) combining multivitamin supplement (vitamin
B6, B12 and folic acid) to donepezil in patients with dementia, found no beneficial
effects on cognition (ADAS-Cog, p=0.34; MMSE, p=0.79) and ADL (Cognitive
Abilities Screening Test [CASI], p=0.51; ADL, p=0.70; IADL, p=0.89) [266] Level I, fair

5.4.4

Combining Acetylcholinesterase Inhibitor with nonpharmacological intervention

The NICE guideline, based on four RCTs concluded that there was a significant
treatment advantage on the cognitive symptoms using MMSE, when AChEI was
combined with cognitive stimulation. [13] Level I, good
In an open label study (n=24), patients who were already on AChEI, had some
additional benefit with the utilsation of multisensory behavioural therapy (MSBT)
in addition to standard psychiatric inpatient care. This study showed that thiscombination may reduce apathy and agitation (p=0.04) and additionally improve
ADL (p=0.04). [267] Level II-1, poor
Combining donepezil and psychosocial intervention was noted to increase
positive effect of quality of life when compared with donepezil alone(n=28, p=0.007). [268] Level II-1, poor

Recommendation
Adding memantine to acetylcholinesterase inhibitors in moderate to severe
Alzheimers disease may be of benefit. (Grade B)
Combining acetylcholinesterase inhibitors with non-pharmacological intervention
may be of benefit in patients with dementia. (Grade B)
71

5.5

ALTERNATIVE/COMPLEMENTARY MEDICATION

A number of other alternative or complementary preparations have beensuggested or investigated in the treatment of dementia. This CPG will review theevidence on these preparations.

5.5.1

Ginkgo biloba

Ginkgo biloba is widely available and, is marketed for ‘cerebral insufficiency’.
There are many different agents of the extract. The potential mechanismsof action include vasoactive effects, antiplatelet activity, increasing neuron
tolerance to anoxia and prevention of membrane damage caused by free
radicals.[13] Level I, good
The NICE guideline concluded from one systematic review (33 placebo-controlled
RCTs, n=3,278) of ginkgo biloba (80 to 600 mg/day for 3 to 52 weeks) and one
new RCT (n=123) of ginkgo (160 to 240 mg/day) that the benefits of ginkgo may
outweigh adverse events.[13] Level I, goodA Cochrane systematic review of 35 placebo-controlled RCTs (n=4247) of
ginkgo biloba (120 mg to 240 mg/day) appeared to be safe with no excess
adverse effects. The evidence that Ginkgo biloba had predictable and clinicallysignificant benefit for PWD or cognitive impairment was inconsistent andunconvincing.[269] Level I, good
Two trials (n=783) on the ADAS-Cog showed no significant difference (p=0.7)
between ginkgo biloba and placebo. However, four trials using the Syndrom
Kurz Test (SKT), noted a significant difference in favour of Ginkgo biloba for the
low dose (MD= -3.1, 95%CI -4.0 to -2.2, p<0.00001, two studies) and highdose (MD=-3.6, 95%CI -3.9 to -3.1, p<0.00001, three studies), and all doses
pooled (MD=-3.6, 95% CI -3.9 to -3.2, p<0.00001, four studies).[269] Level I, good
Two RCTs (n=549) using the Clinical Global Impression of Change (CGIC) scale
showed benefits associated with ginkgo (>200 mg/day) at 24 weeks (NNT=10).
However, another two RCTs (n=652) showed no benefit with the lower dose (<200 mg/day) (OR=1.7, CI 0.9 to 1.7, P=0.2).[269] , Level I, good72

Using the Sandoz Clinical Assessment Geriatric Scale (SCAG) there wasbenefit with ginkgo (< 200 mg/day) compared with placebo at < 12 weeks(MD= -14.70, 95%CI -28.0 to -1.4, p=0.03, n=70), and at 12 weeks(MD= -22.2, 95%CI -29.4 to -15.0, p<0.00001, n=38). The result
from one study using the Crichton Rating Scale showed benefit
for ginkgo (< 200 mg/day) compared with placebo at 12 weeks(MD= -5.0, 95% CI -7.9 to -2.1, p=0.0007).[269] Level I, good
Ginkgo causes bleeding when combined with warfarin or aspirin, raises bloodpressure when combined with a thiazide diuretic and possibly causes coma whencombined with trazodone.[270]

Recommendation
Ginkgo Biloba is not recommended for the treatment of dementia. (Grade A)

5.5.2

Omega-3 fatty acid

Several epidemiologic studies showed a protective effect with increase fishconsumption. The data indicated a beneficial effect of omega-3 or commonly
known as fish oil on the preservation of cognition in AD.[271]Two placebo-controlled RCTs found that omega-3 fatty acid did not show any
effect on the cognitive function (p=0.40) in patients with mild to moderate AD.
However both RCTs showed positive effects in a small group of patients with very
mild AD (MMSE>27, p=0.01) and MCI (p=0.03).[272] Level I, poor;[271] Level I, good
The decline in MMSE was not significant (p=0.4) during the first six
months (−1.0 point for omega-3 [4 gm daily] versus −1.4 points in theplacebo group). In patients with more advanced AD, the decline ratetended to be more rapid in the omega-3 group than in the placebo arm,(−0.9 vs 0 point, p=0.15). In the very mild AD group, there was no significant
treatment effect (p=0.96) for the ADAS-Cog scores over time.[271] Level I, good

Recommendation
Omega -3 should not be used in the treatment of dementia. (Grade A)73

5.5.3Folic acid and Vitamin B

Individuals with AD have been found to have higher plasma homocysteinelevel than age matched control. It has been reported that elevation of plasma
homocysteine levels precedes the clinical manifestation of AD. Folic acidsupplementation causes a significant decline in blood total homocysteine levels.
Many studies are in progress to assess the effects of reducing homocysteinelevels by the clinical manifestation of AD. Folic acid supplementation causes a
significant decline in blood total homocysteine dietary supplements of folic acidalone or in combination with B12 and B6. [51]
The NICE guidelines concluded that folic acid (2 to 15 mg/day, for 1 to 3 months)
had an increased risk of adverse events and this outweighed any potential benefit.
In addition there was insufficient evidence for vitamin B12 treatment for up to fivemonths.[13] Level I, good
A placebo controlled RCT of 18 months duration with high dose vitaminsupplements (5 mg/day of folic acid, 1 mg/day of vitamin B12, and 25 mg/day ofvitamin B6) concluded that these supplements did not slow cognitive decline inindividuals with mild to moderate AD. The ADAS-cog score did not differ between
treatment groups (p=0.52). There was an excess number of adverse events
especially depression in the high-dose group (NNH=10) (p=0.02).[273] Level I, good
A recent systematic review of eight placebo controlled RCTs (four trials of healthyolder people and four with mild to moderate dementia) with or without folate
deficiency, concluded that there was no consistent evidence that folic acid alone
or in combination with vitamin B12 had any effect on cognitive function (MMSE,
WMD=0.4, 95% CI -0.4 to 1.2, p=0.35; ADAS-Cog scales, WMD=0.4, 95%CI-1.3 to 2.1, p=0.63 and Bristol Activity of Daily Living, (WMD=0.6, 95%CI -2.0
to 0.8, p=0.42).[51] Level I, good

Recommendation
Folic acid and vitamin B are not recommended in the treatment ofdementia. (Grade A)74

5.5.4

Vitamin E

NICE guidelines concluded that vitamin E (2,000 IU total daily dose) had more riskof adverse events than benefit in people with dementia. [13] Level I, good
A recent Cochrane systematic review of two placebo controlled trials withvitamin E (2000 IU total daily dose) showed some benefits from Vitamin E withfewer participants reaching any of these endpoints: death, institutionalisation,
loss of two out of three basic ADL or decline of global CDR from 2 to 3
(OR= 0.5, 95%CI 0.3 to 1.0, NNT=6). However, more patients taking Vitamin
E suffered falls (OR=3.1, 95%CI 1.1 to 8.6, NNH= 3). This systematic review
concluded that there was no evidence of efficacy of Vitamin E in the treatment ofpeople with AD or MCI.[79] Level I, good

Recommendation
Vitamin E is not recommended in the treatment of dementia and mild cognitive
impairment. (Grade A)

5.5.5

Huperzine A

Huperzine A, (derived from a Chinese club moss Huperzia serrata) is a linearly
competitive, reversible inhibitor of acetyl cholinesterase. It has both central andperipheral activity with the ability to protect cells against hydrogen peroxide, betaamyloid protein, glutamate, ischemia and staurosporine-induced cytotoxicity andapoptosis. Animal and human studies have shown Huperzine A to be a promising
agent for treating acetylcholine deficit dementia including AD. [274]A Cochrane systematic review of six RCTs (n=454) showed that Huperzine A may
have some positive effects on cognitive function, global clinical status, behavioural
disturbance and functional performance, with no obvious serious adverse events
for patients with AD.[274] Level I, fair)
Four placebo controlled RCTs (n=220) with a dose of 0.3 to 0.4 mg daily up
to 36 weeks, demonstrated a beneficial effect in the cognitive function using
MMSE in AD patients (WMD=2.8, 95%CI 1.9 to 3.8, p < 0.00001). In the review,
Huperzine A was also superior to placebo in ADL (WMD= -7.2, 95%CI -9.1 to-5.2, p < 0.00001). The adverse events of Huperzine A were mild and there wereno significant differences of adverse events.[274] Level I, fair75

A RCT (n=202) comparing Huperzine A (0.4 mg daily) with Vitamin E(200 mg daily) versus placebo plus Vitamin E (200 mg daily) showed improvementon the ADAS-Cog at six weeks (95%CI -5.2 to -2.3) and 12 weeks (95%CI -7.1 to-3.6). Due to the low methodological quality of the included trials, it was concluded
that there was insufficient evidence to recommend Huperzine A.[274] Level I, fair

Recommendation
Huperzine A is not recommended in the treatment of dementia. (Grade A)

76

6.0

NON-PHARMACOLOGICAL TREATMENT OF DEMENTIA

The aim of non-pharmacological treatment or psychosocial intervention is toenhance the person’s self and quality of life. There is no single optimal psychosocial
approach available, and thus a multi-dimensional approach is essential to ensure
effective interventions. This approach should be person-centred and has to be
individualised and tailored to the person’s needs, personality, biography, goals,
strengths and preferences.[275]
Each patient should be assessed whereby a care plan is drawn to address issues,
such as activities of daily living (ADLs) that can maximise independence, enhancefunction, adapt and develop skills, and to minimise the need for support.

Assessment and care-planning approach
The following should be assessed:v

Physical healthv

Depressionv

Possible undetected pain or discomfort

v

Side-effects of medicationv

Individual biographyv

Psychosocial factorsv

Physical environmental factors

Behavioural and functional analysis should be undertaken in conjunction withcaregivers and care workers.
Individual care plans should be developed and recorded in patients’ notes.
These should be reviewed regularly with caregivers and other staff.
Adapted from Taylor C et al, 2009 [276]77In this section, the intervention is grouped according to the therapeutic goals,
with three major domains:v Maintenance of functions:o Adopting strategies to promote independenceo Maintenance of cognitive functioning.
v Management of challenging behaviours - agitation, aggression andpsychosis
v Reduction of co-morbid emotional disorders

6.1

MAINTENANCE OF FUNCTIONS

6.1.1

Strategies for promoting independence

The level of independence for each patient varies and will most likely change withthe stage of dementia and the occurrence of other illnesses. It is not uncommon inmost Asian cultures that the elderly is refrained from more complex activities, andfor others to take over the task for them. There is evidence to suggest that ADL
function often deteriorates below what would be expected by the illness alone.
So caregivers should encourage the PWD to take a more active role and maintaintheir independence for as long as possible by creative means and ensuring theright stimulation.[13] Level I, good
There is little research to draw clear conclusions on specific interventions
for promoting independence. Despite this conclusion, several strategies arerecommended to promote independence. The activities chosen must be
individualised according to patient’s needs, strengths and limitations.[13] Level III, good
Activities that promotes independence include:v

Communication strategies (e.g. cues, memory books)v

ADL skill training/activity planningv

Assistive technology/telecare/adaptive aidsv

Exercise/promoting mobilityv

Rehabilitation programmesv

Combination of interventions
NICE[13] Level III, good78

a. Communication
Good communication means using simple languages as well as short and concretesentences to match the level of comprehension. Non-verbal communication will
include cues and gestures. Communication can be in the forms of written or
pictorial, such as memory book. A memory book consists of individualised images
and simple statements that the PWD and caregiver can use to aid the individual’s
recall and to improve the quality and frequency of communication.
PWD also need to have their vision and hearing tested and corrected withappropriate aids prescribed. For those PWDs who have specific communication
problem, speech and language therapist need to be consulted regarding
appropriate strategies.[13] Level I, goodb. ADL skill training/Activity planning
Activities of daily living (ADL) skill training can promote independence inpersonal care tasks (such as bathing, dressing and feeding) and help themto maximise their remaining skills to participate in their own care. Schedule
voiding helps in the maintenance of functions. [277] Level I, good
ADL skill training involves assessing people’s abilities, their impairments
and their task performance in order to understand the underlying physical,
psychosocial and neurological issues. The programmes include gradedassistance, with the caregiver providing the least amount of assistance needed
at each step to complete the task. Strategies may include verbal or visual cues,
demonstration, physical guidance, partial physical assistance and problem
solving. Professionals trained in assessment and care planning can devise ADL
skill training programmes for use by caregivers and/or care staff. [13] Level I, goodc. Assistive technology/Telecare/Adaptive aids
Assistive technology has been defined as any item, product, system or pieceof equipment that can be used to maintain, increase or improve the functional
capabilities of the person with cognitive, physical or communication
disabilities [13] Level III, good
Telecare involves a range of services including virtual visiting, reminder
systems, home security, and social alarm systems with the overall aims of
avoiding hospitalisation and aiding ageing in place. A telecare package may
involve monitoring activity patterns to detect any changes that may warn ofpotential health changes or of an event such as a fall. Responsive alarms candetect risks by monitoring motion (for example falls) and the presence of fireand gas, and triggering a warning to a response centre or caregiver.[13] Level III, good79

Wandering is one of the manifestations of behaviour problems that lead tocaregiver distress and early institutionalisation of PWD.[278] It is estimated tooccur in 20-25% of community dwelling patients.[279] Electronic tagging andtracking devices such as mobile phone technology and Global Positioning
System (GPS) may be viewed as a way of creating a more secure environment
for vulnerable PWD who are at risk. [280] Level III, poor;[281] Level III, good However, todate no RCT have been carried out to look into the efficacy of electronictagging. [282] Level I, good The use of telecommunication system and computer
technology may also be used to support distance caregiving, although this has
not been fully utilised.[283] Level III, fair
Adaptive aids can range from memory aids to bathing equipment and are
aimed at minimising the impact of physical, cognitive and sensory deficits.
Similarly, low-level technology (for example lights attached to a movement
sensor) is widely used in adaptive aids to minimise risk without the need foraction by the user.[13] Level III, goodd. Physical exercise
A combination of structured exercise and conversation can help maintain mobility
in PWD, but there is no evidence to support the use of either intervention on its
own. The overall impact of physical activities on the symptoms of dementia wasminimal. [164] Level I, good)A Cochrane systematic review based on two RCTs did not find sufficientevidence to suggest that physical activity programmes were beneficial
for PWD. A meta-analysis measured by comparison of function at sevenweeks to six months (Changes in Advanced Dementia Scale [CADS] andADL scores) demonstrated that the pooled results were not significant(95% CI -0.1, -0.7 to 0.5).[284] Level I, poor

e. Rehabilitation programme
A systematic review focused on the effects of motor interventions such as
physiotherapy, occupational therapy and physical education in PWD found thatmotor intervention minimised physical and mental decline. [285] Level II-1, poor
The Singapore guidelines underlined structured activity programmes,
physical rehabilitation and physical exercise as part of non-pharmacologicaltherapies, but did not elaborate further on these activities. [45] Level III, good
In a RCT (n=165) of mild to moderate patients with dementia, it was
found that community based occupational therapy improved dailyfunctioning of the PWD. The NNT were 1.3 at 6 weeks and NNT were
1.5 at 12 weeks. [286] Level I , good80

f. Recreational activity
Recreational activities give an opportunity for PWD to engage in meaningfulactivity, and are often used as a way of facilitating the individual’s need forcommunication, self esteem, sense of identity and productivity. However activities
have to be individualised and adapted to maximise the person’s remaining
abilities. Activities based on previous interests may be more beneficial to PWD
than generic activities. [164] Level III, goodg. Combining interventions
PWD do not only experience cognitive impairment, but also physical,
emotional and social concerns. Interventions need to target multiple aspects
of PWD, the caregivers and environment in order to address the complex
needs of the PWD. [13] Level III, good
A qualitative systematic review of 25 studies relating to 22 programmes
were analysed according to the caregivers on three outcome measures, that is,mental health, burden and competence. Effects of the programmes on PWD werealso looked into and these encompassed mental health, cognitive functioning,
behavioural problems, physical functoning, delayed admission and mortality. The
conclusion drawn was that the caregiver general mental health was positively
affected by combined programmes, while competence appeared promising for
women and minority caregivers. For the PWD, combined programmes improved
mental health and delayed admission to long stay care. [287] Level I, fair

Recommendation
People with dementia need to engage themselves in meaningful activity.
(Grade C)
A combination of interventions that promote communication, mobility and cognition is recommended to facilitate independence in these patients. (Grade B)
Activities have to be individualised and adapted to maximise the person’s
remaining abilities. (Grade A)
Intervention needs to be integrated to target the person’s complex needs,
as well as taking into account the caregiver and environmental concerns.
(Grade A)81

6.1.2

Maintenance of cognitive functions

Cognitive functions are the core symptoms of any definition of dementia. The
key to improving cognitive functioning is linked to the maintenance of day
to day functioning. The evaluation of non-pharmacological interventions inrelation to the maintenance of cognitive function is still at an early stage ofdevelopment.

a. Cognition Oriented Approach
Three major types of approaches with a cognitive focus are:i. Cognitive stimulation entails exposure to and engagement withactivities and materials involving some degree of cognitive processing
ii. Cognitive training is a specific training exercises geared to specificcognitive functions, and includes practice and repetition which may becomputer-assisted
iii. Cognitive rehabilitation include working on personal goals, often using
external cognitive aids and with some use of learning strategies
NICE[13] Level III,good
A Cochrane systematic review of people with mild to moderate AD or VaD foundno evidence for the efficacy of cognitive training.[288] Level I,good Neither was there
evidence for cognitive rehabilitation. However, cognitive stimulation produced amodest improvement in cognitive function for patients with mild to moderatedementia. [13] Level I, good
Cognitive stimulation can be given informally through recreational
activities, or formally through a programme of memory provoking, problemsolving and conversational fluency activities (reminiscence or reality
orientation therapies), spaced retrieval method or face name training. It canbe carried out at home by a caregiver, with no risk to the PWD and withminimal training required.[63] Level I, good82

b. Reality Orientation Therapy
Reality orientation therapy was developed, based on the belief that continuallyand repeatedly telling or showing certain reminders to people with mild tomoderate memory loss will result in an increase interaction with others andimproved orientation. There are two types of Reality Orientation Therapy (ROT):
the 24-hours ROT and formal/classroom ROT.
According to SIGN guidelines, ROT may slow cognitive decline and delay nursing
home placement. The 24-hours ROT method had more benefits than the formal
method. It also suggested that ROT should be administered by a skilled practitioner
on an individualised basis.[63] Level I, good A systematic review found a positive effectof the use of Formal ROT on cognition in the domains of information/orientationand memory.[289] Level I, fair
A cross-sectional study (n=50) of probable AD patients found that ROT whencombined with integrated sessions of computerised cognitive training, showedbeneficial effects on cognitive function, as indicated by an improvement in
the mean MMSE scores on admission and at discharge, at 16.0 (SD 5.6) and17.5 (SD 5.5) respectively, (p=0.005). There was also improvement on ADL
and behaviour (mean ADL scores on admission=4.9, mean ADL scores ondischarge=5.0). [290] Level III, poorc. Reminiscence therapy/life review
In reminiscence therapy, past activities, events and experiences are discussedwith another person or group of people. It usually involves some tangible
prompts such as photographs, household and other familiar items fromthe past, music and archive sound recordings. Life review on the other hand
typically involves individual sessions. The person will be guided through theirlife experiences, encouraged to evaluate them, and may produce a life story
book. Family caregivers are encouraged to be involved in reminiscence therapy.
There was insufficient evidence to evaluate fully the effects of reminiscencetherapy in relation to cognitive function in dementia [13] Level I, good;[63] Level I, goodA RCT (n=102) study was carried out for eight weeks duration. Results
demonstrated that those receiving reminiscence therapy had significant
improvement in cognitive function as measured by MMSE (p=0.015) and affectivefunction by CSDD (p=0.026).[291] Level I, fair83

Recommendation
Cognitive stimulation (encompassing both reality orientation and reminiscencetherapy) may be offered to improve cognitive function for patients with mild tomoderate dementia. (Grade B)

6.2

MANAGEMENT OF CHALLENGING BEHAVIOURS- AGITATION,
AGGRESSION AND PSYCHOSIS

Behavioural and psychological symptoms of dementia is the result of a complex
interaction between the illness, environment, physical health, medication andinteractions with others. It is a major source of distress to patients and caregivers,
and often significantly impairs quality of life for both. These symptoms often remit
spontaneously, but they can also be persistent and severe.
There is lack of evidence to show that pharmacological interventions are effectivein the treatment for BPSD. Recent reports had indicated that the use of typicalor atypical antipsychotics was associated with increased risk of death [291];[292]Hence it is essential for non pharmacological intervention to be the frontline in
the management and treatment of BPSD.
A systematic review showed that caregiver’s education, music, physical exercise,recreation, and validation therapy were able to reduce psychological symptoms
in PWD. [293] Level I, good

6.2.1

Behavioural management approaches

Behavioural management emerges as one of the stronger nonpharmacological approaches, and appears to have lasting effectiveness forthe management of BPSD.
When faced with a patient with challenging behaviours:v
Review possible physical causesv
Examine medication listv
Look for contributing environmental factors
v
Consider psychiatric diagnosis
v
Focus on target behaviors to be addressedv
Reserve medications for situations where the safety or well being of
the patient or others is at risk.
(Adapted from Omelan 2006, Level III, good)84

Most of the evidence came from studies targeting co-morbid depression andanxiety in dementia. The evidence in relation to challenging behaviour is lessextensive, and largely derives from single case series. There is some evidence
that the intervention may need to involve working through others, eitherfamily caregivers or paid care workers. It may, inevitably, involve elements oftraining and support. Consideration should be given to providing access tointerventions tailored to the person’s preferences, skills and abilities. [13] Level III, goodA systematic review of four RCTS of the behavioural management approach for thetreatment of depression in PWD at various stages of dementia severity concluded that
there was no evidence for a significant reduction in disruptive behaviour among thenursing home residents or those in the community.[63] Level I, good

6.2.2

Music therapy

Both the NICE guidelines and a Cochrane systematic review based on five RCTs
found it difficult to draw any conclusions on the role of music therapy in the careof older PWD. [13] Level I, good ,[294] Level I, good)
In a systematic review of eight small sample size studies, with variations in theapplication of preferred music interventions (classical music or taped music),
compared with no music or other types of treatment conditions (family generated
video, social interaction or hand massage), music listening to personal preferences
generally had some positive effects on decreasing agitated behaviour in thosewith dementia. [295] Level I, poor
In a RCT (n=59), the intervention group received 30 music therapy sessions(16 weeks of treatment), and the control group received educational support
or entertainment activities. The NPI total score significantly decreased in theintervention group at eight and sixteen weeks (p=0.002). The effect persisted
four weeks after end of treatment (p=0.0007), suggesting that subjects allocatedto music therapy maintained their improvement over time. Specific BPSD
(delusions, agitation, anxiety, apathy, irritability, aberrant motor activity, and nighttime disturbances) also significantly improved. [296] Level I, fairMusic therapy stood out as an effective treatment of behavioural symptoms
of dementia, especially when tailored to reflect participants’ previous tastes.
In a systematic review of nursing home residents exposed to a range ofmusical styles in different settings, music could reduce irritability, fearand depression. When the ratings of irritability, depression and fear werecombined, the mean effect size for soothing music was substantial at 0.8(range 0.7–0.9). The mean effect sizes were 0.3 (range 0.1–0.5) for 1930s
jazz and 0.4 (range 0.3–0.5) for pop songs. [293] Level I, good85

6.2.3

Physical activity/mobility programme

The SIGN guidelines recommended a combination of structured exercise andconversation to help maintain mobility in PWD. [63] Level I, good 63
A RCT (n=90) which looked into two types of physical activities (gentle
comprehensive and walking) and a conversation group, found a higher
positive affect as measured by the Observed Affect Scale (OAS) in the
gentle comprehensive exercise group (15% in physical activity group > 9%in conversation group, (p<0.05). Negative affect scores on the Alzheimers
Mood Scale (AMS) were 12% lower in the exercise group than the walking
group and 21% lower than the conversation group (p<0.05). There were no
significant differences for OAS negative affects or AMS positive affects forthe physical activity groups noted. [293] Level I, goodA randomised study (n=45) of moderate to severe AD patients assigned either
to comprehensive individual exercise, supervised individual walking, or social
conversation, demonstrated that 35% of participants had CSDD score < 7, after
16 weeks of treatment. There was also significant changes in the Dementia
Mood Assessment Scale score (DMAS) (p=0.0003) and the OAS positive affect(p=0.0092) after two weeks. The OAS negative affect was not significant(p=0.1217). [297] Level I, fair

6.2.4

Validation therapy

Validation therapy is an approach to communicate with disorientated elderly
people, which involves acknowledging and supporting their feelings in whatevertime and place that is real to them, even if this may not correspond to their “hereand now” reality.[63] Level I, goodA systematic review based on four RCTs (n=144), did not find any significant
differences between validation and social contact or between validation and usual
therapy.[298] Level I, good
The NICE guidelines also concluded that there was insufficient evidence torecommend validation therapy in the treatment of dementia.[13] Level I, good86

6.2.5Multisensory stimulation and/or Snoezelen therapy

The rationale for multi-sensory stimulation and/or Snoezelen therapy, lies in the
proposition that the provision of a sensory environment for people with dementia
places fewer demands on their intellectual abilities but capitalises on theirresidual sensorimotor abilities.
There was very little research on Snoezelen therapy or multisensory
stimulation in dementia. [13] Level I, good However, two high quality RCTs analysedin a systematic review showed evidence that Multi Sensory Stimulation/
Snoezelen in multi-sensory room reduced apathy in people in the latter
phases of dementia. [299] Level I, good
An updated Cochrane systematic review included two new RCTs. There
was no effect on behaviour, mood, cognition and communication in either
the short or long term follow-up of session based snoezelen programme.
Likewise, the 24-hour integrated snoezelen care also failed to demonstrate
any effects on the behaviour, mood and interaction in PWD. [300] Level I, good A
more recent review concluded that multisensory stimulation proved noteffective in treating challenging behaviours in dementia. Some patients are
disturbed by its random lights, sounds and shapes. [293] Level I, good

6.2.6

Massage and touch therapy

A Cochrane systematic review based on two small RCTS found evidence to support
the efficacy of hand massage for immediate and short-term reduction of agitatedbehaviour, and the addition of touch and verbal encouragement to eat, for thenormalisation of nutritional intake. Massage and touch have been suggested asa non-pharmacological alternative or supplement to other treatments, to reduceor manage anxiety, agitated behaviour and depression associated with dementia.
It has also been suggested that massage and touch may counteract cognitive
decline.[301] Level I, good

6.2.7

Aromatherapy

Aromatherapy is the use of pure essential oils (such as lavender and melissa) tohelp relieve health problems and improve the quality of life in general. The healing
properties of aroma therapy include promotion of relaxation and sleep, reliefof pain, and reduction of depressive symptoms. Aromatherapy has been used
to reduce disturbed behaviour, to promote sleep and to stimulate motivational
behaviour of PWD.
87

A RCT on aromatherapy demonstrated a significant effect on measures ofagitation, using Cohen-Mansfield Agitation Inventory (CMAI), and NPI, in favourof interventions. However more large scale RCTs are needed to demonstrate theeffectiveness of aromatherapy.[302] Level I, good
Both the SIGN guidelines and a recent systematic review did not find any
good studies on the role of aromatherapy in reducing the core and associatedsymptoms of dementia.[63] Level I goodI;[293] Level I, good

6.2.8

Light therapy

Sleep disturbances is common among PWD and give rise to greater riskof mood disorders, poorer daytime functioning, poorer quality of life andincrease risk of falls and injuries. It is equally distressing to the caregivers.
Available medications proved to be ineffective, with significant adverse
effects. Bright light which affects the production of melatonin may be a safer
alternative. However three RCTs did not show any consistent benefit of bright
light therapy on sleep or agitation.[63] Level I, good
A crossover RCT (n=66) of moderate to severe dementia, exposed to four light
conditions (morning bright light, evening bright light, all-day bright light, andminimum standard light) for three weeks, was performed. It was found that nighttime sleep increased significantly, with the increase most prominent in severeor very severe dementia (mean increase 16 minutes (p=0.008) for morning,and 14 minutes (p=0.01) for all-day. Effect on daytime sleepiness was howeverinconsistent. [303] Level I, fair
A RCT (n=189), long term trial (3.5 years), involved patients with dementia
exposed to four types of interventions: light, melatonin, combinationand placebo. It was found that light has modest benefits on cognition(mean of 0.9 points, 95%CI, 0.0 to 1.7) or 5% improvement on the
MMSE and depressive symptoms (1.5 points, 95%CI, 0.2 to 2.7) or 19%
improvement on the CSDD. Melatonin has effects on sleep latency (shortenedby 8.2 minutes, 95%CI, 1.1 to -15.4) or 19% improvement, and increased
sleep duration by 27 minutes (95%CI, 9 to 46) or 6% improvement.
Combination therapy reduced aggressive behaviour (3.9 points, 95%CI, 0.9
to 6.9) or 9% improvement on the CMAI, increased sleep efficiency by 3.5%
(95%CI, 0.8 to 6.1), and improved nocturnal restlessness by 9%(3.5%, 95%CI, 0.3 to 1.8). Adverse events were dizziness and irritability. [304] Level I, good88

Recommendation
Psychosocial interventions should be tailored to individual needs, preferences,skills and abilities of the people with dementia. (Grade A)
Specific psychosocial interventions such as music and physical activity
programmes can be beneficial in managing behaviour and psychologicalsymptoms of dementia. (Grade A)
Multisensory stimulation is not effective in Behaviour and PsychologicalSymptoms of Dementia, and may be harmful in agitated patients. (Grade A)
There is insufficient evidence to recommend massage and aromatherapy.
(Grade A)
There is insufficient evidence to recommend bright light therapy for sleep
disturbances or behavioural and psychological symptoms of dementia.
(Grade A)

6.3

REDUCTION OF CO-MORBID EMOTIONAL DISORDERS ANXIETY AND DEPRESSION

Symptoms of depression and anxiety are common in dementia, and areassociated with decreased independence and increased risk of nursing home
placement. In individuals with dementia, the prevalence of anxiety ranges from
5% to 21% for anxiety disorders, and from 8% to 71% for anxiety symptoms.
Cognitive behavioural interventions have been used effectively for many problems(including depression, reduced social skills, acute stress disorder, and problem
behaviours) in other cognitively impaired populations. Caregivers may play animportant role in the implementation and success of Cognitive behaviour therapy(CBT) in this population.[305]Cognitive behaviour therapy delivered by trained mental health professionals
may be used in the early stages of dementia but is less likely to be effectivein the latter stages of dementia or in nursing home setting. However there
is a lack of RCT. [13] Level I, good In a systematic review of 19 studies looking into
psychosocial intervention, one RCT on behavioural therapy showed limited
evidence that, CBT approach using the Behaviour Therapy–Pleasant Events
and Behaviour Therapy–Problem Solving, reduced depression in people withprobable Alzheimers Disease living at home with their primary caregiver. [299] Level I, good89

Bright light therapy had also been looked into as treatment of depression
in dementia. In a cross-over RCT (n=66) of patients with moderate tosevere dementia exposed to light for duration of three weeks, there wasa significant sex differences found in the CSDD scores in response toevening light (p=0.003), all-day light (p=0.001), and standard light(p≤ 0.001). Depressive symptoms were lowest for women and highest
for men during morning light. However, findings do not support the useof ambient bright light therapy as a treatment for depressive symptoms
in PWD. [306] Level I, fair
A Cochrane review of four RCTs (n=144) on reminiscence therapy showedsignificant improvement in cognition, mood and functional ability after four to
six weeks of treatment among PWD. Participating caregivers of PWD in thereminiscence group also reported lower strain. No harmful effects were reported
in the outcome measured. However the review concluded that more robust
studies are needed. [275] Level I, good

Recommendation
Cognitive behaviour therapy may be used to treat depression in early dementia.
(Grade B)
Reminiscence therapy can be used in those with depression and anxiety.
(Grade B)

90

7.0

CARE ENVIRONMENT

Environment plays an important role in the development of behaviour problem indementia. Most people suffering from dementia in this country are still cared forat home by their family members, but institutional care may be inevitable as thedisease progresses with changes in the social and family structure.

7.1

ENVIRONMENTAL DESIGNS FOR PEOPLE WITH DEMENTIA

Designs of living environment for PWD and modification of physical environmentof their residential areas are largely based on agreed good practice. (Refer toAppendix 12)
There are no RCTs or well designed controlled studies that address the issue ofenvironmental designs, whether in the institution or in the domestic setting, thatare appropriate for those with dementia. Most systematic reviews failed to show
any benefits, reflecting the lack of high quality research rather than an actual lackof benefit. [307] Level I good ;[282] Level I, good
Environmental modifications, such as, exit modification in the form of subjective
barriers has been used to reduce problem behaviours. These include using
mirrors, floor stripes and camouflage of door furniture. It may provide an
inexpensive, safe, effective and ethical alternative to drugs or restraints in the
management of wanderers. However, a Cochrane systematic review found noevidence that subjective barriers prevent wandering. In fact, there is a possibility
that such barriers cause psychological harm. [307] Level I, good
The NICE Guidelines based recommendations on four descriptive studies looking
into environmental modifications and the use of adaptive aids and other qualitative
evidences using interview and observation methods. It looked into the designsof living and care environment for the PWD. Combining adaptive devices withcaregiver’s education and environmental modifications were reported to improveoutcomes in independence for PWD, and at the same time reduced caregivers’
stress. When considering environmental design, it was noted that due importanceshould be given to the differences in individual requirements, which may differ
according to the individual’s personal history, culture, religion, and the degree of
the impairment. [13] Level I, good
91

The SIGN guidelines [63] Level I, good reviewed the same papers but concluded
that changes made to the environment could have a positive impact on theassociated symptoms of dementia. However findings of the studies wereimpaired due to lack of comparison groups, non-equivalent comparisongroups and small sample size.
A Cochrane systematic review reported success in terms of adopting a lot ofstrategies, but outcomes in the area of behavioural difficulties or caregivers’
stress and institutionalisation were unknown. [282] Level I, good
The NICE and SIGN guidelines have identified that user involvement inenvironmental redesign is useful and provides insights. There is currently noevidence on cost effectiveness of environmental redesign related to PWD andtheir caregiver. [13] Level III, good ;[63]Level III, good

Recommendation
Environmental modification is helpful but needs to be individualised to theperson and the degree of impairment, preferably after occupational therapist
assessment. (Grade B)
The recommended and non-recommended features are listed in Appendix 12

92

8.0

INTERVENTIONS FOR CAREGIVERS

Caring for a PWD is very challenging, but it can be equally rewarding. The
role of the caregiver has been increasingly recognised as the care of the PWD
is dependent on them. There is evidence to show an increase in potential
costs, both direct and indirect, as a result of psychological distress, physicaland mental ill-health, as well as increased mortality among the caregivers. In
addition, interventions of caregivers would also benefit the patient, in termsof reducing BPSD, and nursing home placement. Hence the management ofdementia should also focus on helping the caregivers. A “one-size-fits-all”
approach is deemed ineffective while specific interventions that are tailored
towards the needs of the caregiver, implemented at the relevant trajectories
of illness, would be most effective.

93

The Michigan Dementia Coalition-Caregiver Support Workgroup, following ameta-analysis report, made the recommendations for an effective caregiverintervention, as outlined below:
For effective caregiver interventions:
1. Conduct Assessment- a thorough assessment of the caregiver and thecare giving situation to determine an effective intervention plan that is best
suited for the individual circumstance.
2. Utilise Multi-Component Interventions*- using multiple interventions
or techniques simultaneously, increases the chances of effectively
addressing the variety of caregiver needs.
v Psychoeducation

Structured program providing information about the disease process,resources, services and training on how to respond effectively to diseaserelated behaviours.
      
v Psychotherapy
Therapeutic goal to develop problem-solving abilities and help caregiver
re-engage in pleasant and positive activities.
v Supportive intervention

Unstructured support groups to focus on building rapport among
participants and creating space to discuss problems, successes, andfeelings regarding caregiving.

v Respite/day care

In-home or site-specific supervision, providing assistance with ADL to give
caregiver time off.

v Care recipient training

Activity therapy programs designed to improve competence of person withdementia.

3. Offer Interventions with Higher Intensity- more frequent contacts overa longer period of time are more likely to alleviate caregiver depression andcare recipient symptoms.
4. Promote Consumer-Directed Interventions. Caregivers who have morechoice, control, and flexibility in their home care options are significantly
more satisfied with overall service options.
(Modified from Michigan Dementia Coalition-Caregiver Support Workgroup,) [308] Level III

94

Some of the above Multi-Component Interventions are currently being offered by
the Alzheimer Disease Foundation of Malaysia and several patient support groups
in Malaysia.
It had been demonstrated that interventions which involve the PWD along side
the caregiver appear more effective than interventions that involve the caregiver
alone. Among the components of interventions, while psychological therapies
had the best outcome on caregiver depression, multi-component interventions
had more robust effect on caregiver burden and well-being. [13] level I, good Evidence
suggests that caregiver intervention can delay the need for nursing home
placement [63] Level I, good
The Resources for Enhancing Alzheimers Caregiver Health study II (REACH II)
is a large RCT (n=642) that looked into the effects of a structured andintensive multicomponent interventions (provision of information, didactic
instruction, role playing, problem solving, skills training, stress management
techniques, and telephone support groups) against usual intervention(educational material and two telephone calls). The primary outcome wasa quality-of-life indicator (five domains: caregiver depression, burden, selfcare, social support and care recipient problem behaviours) at six months.
Differences in net improvement between the groups favoured intervention
for both depression (2.6 points net improvement), and problem behaviours(1.5 point net decrease). Secondary outcomes were caregiver clinicaldepression and institutional placement of the care recipient. The intervention
group was found to experience significantly greater improvement in qualityof life than those in the control group (p <0.001 [Hispanic], p=0.0037[Caucasian] and p=0.003 [African-American]). The prevalence of clinicaldepression was lower among caregivers in the intervention group(12.6% vs. 22.7%, p=0.001), but there were no statistically significant
differences in institutionalisation at six months (p=0.118). [309] Level I, good
A meta-analysis based on six RCTs on psychosocial interventions (counsellingand personal assistance with problem solving), plus offering caregivers a choiceof various support strategies and support services, indicated that the odds ofinstitutionalisation (OR=0.60, 95%CI 0.4 to 0.9, p=0.004) were less comparedto those who received usual care. However time to institutionalisation was not
significant (MD=1.6, 95% CI -0.4 to 3.5, p=0.11). This study concluded thatinterventions should be individualized, intensive, and designed to meet the uniqueneeds of patients and their caregivers at the appropriate time.[310] Level I, good95

Another RCT comparing counselling and support intervention to usual care
had reported a 28.3% reduction in the rate of nursing home placement(HR 0.7, p=0.025) with a difference in median time to placement of 557
days [311] Level II-1, fair
Beneficial effects of caregiver interventions can continue beyond nursing home
placement. Burden of the intervention group (comprehensive counselling condition,n=203) was significantly lower than the burden of the usual care group (n=203)
at each point after nursing home admission (p<0.03). There was significant
reduction of depressive symptoms amongst the caregivers after nursing homeadmission (p<0.001) and for the accelerated decrease of depressive symptoms
after nursing home admission (p=0.009). [312], Level II-1, goodWith regards to the duration of effect, caregivers with high morbidity had lesstotal burden and strain 6 months after intervention compared with controls,
showing increased burden while at 12 months. All the indices of burden except
disappointment were reduced. [313] Level II-1, goodA RCT of PWD-caregiver dyad (n=81) was randomly allocated either to receive
the home based intervention (information on dementia, guidance on behaviour
management, a single psychiatric assessment and if needed psychotropic
medication) or to a waiting list group. The intervention group showed a significant
reduction in the outcome measures of General Health Questionnaire (GHQ)(21.1, 95% CI 22.1 to 20.2) and distress due to behavioural disturbances (NPI-D
scores) (22.0, 95%CI 23.5 to 20.4). There was a non-significant reduction in the
Zarit Burden Score (ZBS), Everyday Abilities Scale for India (EASI) and behaviouralproblems in the subject (NPI-S) scores. There was also a non-significant reductionin the total number of deaths in people with dementia in the intervention arm(OR=0.3, 95%CI 0.0 to 1.0) observed [314] Level I, good

Recommendation
An evaluation of the caregivers’ needs should be carried out on a routine
basis. (Grade A)
Multi-component* caregiver intervention should be individualised and intensive
to meet the needs of patients and their caregivers. (Grade A)*Refer to Michigan Dementia Coalition-Caregiver Support Workgroup

96

8.1

EDUCATIONAL INTERVENTIONS IN THE MANAGEMENT OFPEOPLE WITH DEMENTIA AND THEIR CAREGIVERS

Information about the disease process, resources, services, and training on how to
respond effectively to disease-related behaviours should be provided on a regularbasis, preferably as a structured programme. Both the PWD and the caregivers
are likely to benefit from enhanced knowledge about the disease, the care givingrole, and the available resources. Information is effective as an early intervention
strategy to delay more expensive supports. Caregivers may also benefit fromtraining in general problem-solving skills as well as interventions that target
behavioural problem or caregivers’ emotional response. Psychoeducation alongwith psychotherapy should be used whenever possible, as research indicatesthat these two interventions had the most consistent positive effects of caregiverinterventions.
There is lack of evidence on educational interventions targeted solely for PWD.
Education does appear to be a component of a few other programme including
support groups which have had a primary focus on outcomes of depression
and anxiety rather than on knowledge and awareness. Most of the researchsummarised relates to interventions for staff and family caregivers.
Two RCTs and few other descriptive studies that addressed the issue of educational
interventions to PWD and their caregiver were reviewed in NICE guidelines[13] Level
I, good)
and also in the SIGN guidelines[63] Level I, good. It was concluded that PWD
and their caregiver are entitled to receive relevant information. A recent narrative
review found that psycho-educational or psychotherapeutic approaches have agreater effect than those that use education alone or other type of interventions.
Psychoeducation programme had the best outcome in relation to depression
apart from psychological therapy (CBT).[315] level III, poor

Recommendation
Educational intervention to both patients and caregivers should be offered.
(Grade C)
Psychoeducation interventions are listed in Appendix 13

97

9.0

BASIC LEGAL AND ETHICAL ISSUES

Most patients in the early or mild stage will still have insight into his or her
condition. As the disease progress, the mental impairment of dementia bringsa gradual loss of understanding, including that of the person’s own feelings
and behaviour. There will also be a loss of autonomy as patient become more
dependent on others. Ethical problems may arise in the context of dementia careas a result of the loss of autonomy and personal freedom.
Underlying the concept of autonomy are two fundamental issues: disclosure ofdiagnosis and capacity of patient to make decisions.

9.1

Disclosure in dementia or truth telling

Following case identification, the fundamental question is how to disclose thediagnosis of dementia. Most physicians are uncomfortable about disclosure
and often would use the patient’s relatives and caregivers as a proxy when
considering discussion of the diagnosis, treatment and prognosis of the illness,without necessarily having the patient’s consent. [316]Although patients generally would like to know the truth about their own medical
condition, the rights of those who do not want to know should also be respected.
Health care professionals should therefore seek to understand their patients’preferences with respect to the diagnosis of dementia and act appropriately
according to their choice. Studies have shown that the vast majority of patientswith mild dementia wished to be fully informed. [45] , Level III, fair
Unless a patient suffering from dementia explicitly declines to know thediagnosis, the default mode should be to inform truthfully as it will enable
the patient to:a. Plan for optimal life experiences in remaining years of intact capacities
b. Designate and appoint a surrogate decision maker to take over the makingof treatment decision upon eventual incompetencec. Settle personal financial and legal matters
d. Participate in treatment decisions
e. Consider possible enrolment in research programmes andf. Participate in informed consent process
98Results from a postal survey of 389 GPs, and 239 neurologists andpsychiatrists demonstrated that the two professional groups (70% of the GPs and
77% of the specialists) strongly agreed that ‘‘patients with dementia should be
informed early because of the possibility to plan their lives’’. This similar survey
also reported in favour of a timely disclosure - an attitude that is more pronounced
among younger physicians. [317] Level III, fair
In a cross-sectional study to evaluate relatives’ attitudes (n=71) towards informing
patients with AD about their diagnosis, 60.6% relatives spontaneously requested
that patients not be fully informed, and 54.9% did not want the patient to be told
about the lack of disease modifying treatments. Justifications were related to theonset or worsening of depressive symptoms in the patient. A significant degree of
denial of AD diagnosis was found in 23.9% relatives. [318] Level III, fair
A small cross sectional study (n=10) of PWD and caregivers highlighted
deficiencies in current practice of truth telling and the complexity of the processof disclosing a diagnosis of dementia in an appropriate manner. There is a need to
tailor the process of disclosure to individual patients and caregivers. [319] Level III, poor
The Singapore guideline stated the importance of knowing patients
preference on the disclosure of the truth, the process of telling, theimportance of support after disclosure and reason for disclosure. [45] Level III, fair

Recommendation
Patient’s preference on the disclosure of the truth should be elicited.
(Grade C)
The process of truth telling should be done in an appropriate and sensitive
manner. (Grade C)
Following disclosure to patient, support should be provided to patients andcaregivers. (Grade C)

99

9.2

CAPACITY AND DECISION MAKING

Respect for autonomous decision making is a fundamental ethical and legal
right of a mentally competent individual. This right of self-determination should
be respected to the fullest possible extent, even in dementia. When affected bydementia, the key to a patient’s right of autonomy is the presence of adequate
decision-making capacity [45] .
A diagnosis of dementia does not automatically imply a loss of decision making
capacity, which is specific to each patient and to each medical decision.[45]Capacity can be assessed by the patient’s ability to:v Understand the information relevant to the decision.
v To retain this informationv To use or weigh that information as part of the process of making thedecision orv To communicate his decision (whether by talking, using sign language or
any other means)
NICE[13] Level III, good
Health and social care professionals should always seek valid consent from PWD.
People with dementia should be given the opportunity to convey information
in a confidential manner while he or she still has capacity. The PWD and theircaregivers should be educated on the use of advance statements (which allow
people to state what is to be done if they should subsequently lose the capacity to
decide or to communicate) and advance decisions to refuse treatment. [13]In dementia, the key to a patient’s right of autonomy is the presence of adequate
decision-making capacity. In Malaysia, once a patient is found to be mentallydisordered/incapacitated, the provision of the Malaysian Mental Health Act 2001
(Part X- proceedings in inquires into mental disorder; section 58 to section 75)
should be followed, which aims to protect the patient from his or her own harmful
decisions or actions.

Recommendation
While the people with dementia still has the capacity, early consideration foradvance statements and advance decision to refuse treatment should beplanned.( Grade C)
When a people with dementia loses decision making capacity, it is important toprotect the person from their own harmful decisions or actions. (Grade C)
100

9.3

PALLIATIVE AND END OF LIFE CA R E F O R P E O P L E
W I T H DEMENTIA

The term palliative care encompasses not only the physical symptoms, but also
the psychological, social and spiritual aspects of non-curable diseases. The aim
is to achieve “the best quality of life for patients and their families” from anearly point in the disease [320]. The palliative care approach equate to good-quality
person-centred care in dementia. The NICE guidelines advocates specialist
palliative care for dementia as that for cancer, particularly towards the end of thepatient’s life. Both approaches include palliative interventions, which are noncurative treatment aimed at making the patient comfortable, and maximisingquality of life, as well as supporting caregivers during their bereavement process.
[13] Level I, good

Palliative care in dementia should begin from the time of diagnosis, up to the timeof death. Communication about these issues should start as soon as possible,
ideally at time when the diagnosis of dementia was made because individuals
with dementia eventually lose the ability to make independent decisions about
their future care. However, doctors are reluctant to adopt adequate palliative carefor people with dementia.
A case control study (n=303) comparing palliative care measures(pain medications and oxygen) in PWD found that only 11% of were given palliative
care measures compared to 38% of subjects who were not demented. This finding
did not vary significantly with the severity of dementia [321] Level II-3,good

9.3.1

Artificial Nutrition and Hydration

As dementia progresses, the muscles of the throat gradually cease to work
properly, leading to swallowing difficulties, gagging, choking, loss of voice, ordifficulty catching one’s breath. This will compromise nutrition and hydration.
People with severe dementia also often lose interest in food and drink. The
challenge is whether or not artificial nutrition and hydration should be instituted.
However artificial nutrition and hydration is not without problems as findings
had shown that it could result burdensome complications such as aspiration
pneumonia and pressure sores. Patients often have to be restrained during
artificial nutrition and hydration, and this may also prolong survival.
101

A review of the evidence found no relevant RCTs comparing tube feeding andoral feeding. On the available data, it was concluded that the best evidence
did not support the use of tube feeding in dementia. There is a need toweigh the risk and benefit of artificial nutrition and hydration, as it is seldom
warranted for patients in the final stages of dementia. Food thickeners withappropriate posture and feeding techniques can be used in patients withdysphagia.[13] Level I, good
A survey of 376 severely demented patients (Global Deterioration Scale
Level 7) showed that 24.5% (92) were fed by nasogastric or gastrostomy
tube. Despite reservation concerning its utility, feeding tube is reasonably
widespread in patients who have reached the stage of severe dementia.
[322], Level III, fair

In an observational study of severe dementia (n=178, six weeks duration), a highlevel of discomfort was found at the time of decision to forgo artificial nutritionand hydration, but the discomfort reduced days thereafter. More than half ofthe patients (59%) died within one week after the decision was made to forgo
artificial nutrition and hydration. Discomfort level were higher in males (1.7 points
higher), symptoms of dyspnea and/or restlessness (2.6 and 3.3 points higher,
respectively), pain and dehydration (1.5 and 1.3 points higher, respectively) andbeing awake (3 points higher). [323] Level III, fair)

Recommendation
It is important to individualise and balance the risk-benefit ratio of artificial nutritionand hydration (nasogastric and gastrostomy tube feeding).(Grade C)
Alternative conservative measure e.g. posturing, feeding technique and foodthickener should be considered. (Grade C)

9.3.2

Pain

Pain is a common symptom and there is evidence that pain goes undetectedamongst PWD. This reflects difficulties with communication and the recognitionof pain by clinicians. There is evidence of under-treatment of pain. [13]Self-reported pain, although still attainable, may be less reliable in those withmild to moderate dementia than in cognitively intact elderly people, depending on
when it is assessed. [324]102The management of pain in dementia should be the same as it is in otherbranches of medicine. The WHO analgesic ladder is a useful resource (refer toAppendix 13). In the final days of life, a palliative care pathway might encourage
appropriate management of symptoms, including pain. [13] Level I, goodAn eight week randomised, double-blind, cross-over trial of patients withmoderate to severe dementia (n=25) compared acetaminophen (3,000 mg/d)
with placebo. Behaviour and emotional well-being were assessed using
Dementia Care Mapping and CMAI. As needed psychotropic medication use
was aggregated from medication logs. The conclusion was that untreated pain
inhibits activity in nursing home residents with moderate to severe dementia.
Pain treatment in this group of untreated pain may facilitate engagement withthe environment. [325] Level II-1, fair
A three month comparative study (n=163) emphasised the importance ofsystematic pain assessment in long-term care using Pain Assessment
Checklist for Seniors with Limited Ability to Communicate (PACSLAC) in
improving pain management practices and decreasing caregiver distress.
[326] Level II-3 , fair

A quasi-experimental study of older adults (n=126) showed that cognitively
impaired participants reported less pain than cognitively intact participants
after movement but not at rest. The findings from the study support the use ofmultidimensional pain assessment in PWD. [324] Level II-3, fair
A systematic review identified 12 observational pain assessment scales for theelderly with severe dementia and evaluated the psychometric properties andclinical utility of these instruments. It concluded (based on the psychometricqualities and criteria regarding sensitivity and clinical utility) that Pain Assessment
Scale for Seniors with Severe Dementia (PACSLAC) and DOLOPLUS-2 are themost appropriate scales currently available. [327] Level I, good

Recommendation:
High index of suspicion of the presence of pain and the use of pain assessment
scales will be helpful to improve pain detection. (Grade B)
Pain in dementia should be treated, the cause of pain determined andmanaged along WHO analgesic ladder. (Grade C) (Refer to Appendix 14)103

9.3.3Treatment of Infection

Pneumonia is common and there is evidence that treatment does not improvemortality and may even cause substantial suffering. However in certain
circumstance depending on the severity of the dementia, co-morbidity, immobility,
nutritional status and the virility of the infection, antibiotics may be helpful. [13] Level I, good
In a case control study of patients with severe dementia (n=303) against
patients without dementia, antemortem data were collected. It was foundthat 53% of PWD receive antibiotics compared to 41% of those without
dementia. It was concluded that use of systemic antibiotics is prevalent in
the treatment of patients with late stage dementia, despite the limited utility
and discomfort. [321] Level II-3, fair

Recommendation
Antibiotics for treatment of infections and pneumonia in severe and latedementia should be individualised taking into consideration of the severityof dementia, co-morbidity, nutritional status, mobility status and virility of theorganism. (Grade C)

9.3.4

Restraints

Restraints are used to protect patients with severe dementia from harming
themselves because of their behaviour. However the use of restraints can causesome potential problems including risk of harm and injury, further cognitive andfunctional decline, leading to ultimately loss of independence, as well as loss ofconfidence and self esteem [45] Level III, poor
A cross sectional study of patients with advanced dementia (n=141),
described the last month of life of these patients in long-term care, and theclinical decisions in the management of their end-of-life events. Some formof physical restraint was used on 58.2% (bed-rails and other immobilisers)of patients. Attention to physical suffering was found to be fairly good.
However, during the last 48 hours a number of inappropriate interventions
were provided. These include tube feeding (20.5%), intravenous hydration(66.6%), antibiotics (71.6%), and life-sustaining drugs (34.0%). [328] Level III, poor

Recommendation
Physical restraint should be used sparingly and individualised. (Grade C)104

9.3.5

Cardio-Pulmonary Resuscitation

Cardio-Pulmonary Resuscitation (CPR) should not be pursued actively
because:
1. The futility and burdensome nature of CPR in severe dementia.
2.

The evidence that, in severe dementia, CPR is unlikely to be successful.

3. Evidence from the US show that most older people are against life
sustaining treatments. [13] Level I, good
A cross sectional survey of Chinese family caregivers (n=51) on knowledge
about CPR, found that family caregivers had poor knowledge about life sustaining
treatments, with 59% unable to name any feature of CPR. Most relied on theirown views in decision-making rather than on what they thought their relative
would have wanted. [329] Level III, poor

Recommendation
Health care professional should have more discussion about
Cardio-Pulmonary Resuscitation and make individualised decision after
taking consideration of all factors. (Grade C)

105

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Appendix 1
SEARCH STRATEGY
The following free text terms or MeSH term were used either singly or in combination:
Alcohol AND dementia; Dementia AND “Down’s Syndrome”; “Learning disability” ANDdementia; “Intellectual disability” AND dementia; “intellectual disability” and dementia,
Dementia AND smoking; depression” AND risk AND dementia; “Early detection” ANDdementia; “early recognition” AND dementia; “early diagnosis” AND dementia; (Risk
OR “risk factor” OR prevention) AND dementia AND diabetes”; obese OR (Risk OR“risk factor” OR prevention) AND dementia AND obes*”; Risk OR “risk factor” OR
prevention} AND dementia AND homocysteine”, Risk OR “risk factor” OR prevention)
AND dementia AND folate; Risk OR “risk factor” OR prevention) AND dementia AND
exercise; (Prevention OR delay) AND dementia AND weight, (Prevention OR delay)
AND dementia AND education; “memory clinic” OR “memory clinic attendees”; (“Latedementia” OR “severe dementia” OR “end of life dementia” OR “terminal dementia”)
AND restraints; (Risk OR “risk factor” OR prevention) AND dementia AND (hypertension
OR blood pressure); (“Alzheimers disease” OR Dementia OR Alzheimer) AND “Decision
making capacity”; (“Alzheimers disease” OR Dementia OR Alzheimer) AND (Truth OR“truth telling” OR “disclosure); (“Late dementia” OR “severe dementia” OR “end of life
dementia” OR “terminal dementia”) AND “Artificial nutrition” OR hydration; (“Latedementia” OR “severe dementia” OR “end of life dementia” OR “terminal dementia”)
AND “treatment of pain”; (“Late dementia” OR “severe dementia” OR “end of life
dementia” OR “terminal dementia”) AND “treatment of infections”; (“Late dementia”
OR “severe dementia” OR “end of life dementia” OR “terminal dementia”) AND
resuscitation; (“Head injury” OR “brain injury” OR “traumatic brain injury”) AND(dementia OR “Alzheimers disease”); (“Mental stimulation” OR “mental activity” OR“mental training”) AND dementia; “Social engagement” AND (dementia OR “dementia
risk”); Dementia AND “caregivers” OR “caregiver intervention” OR “psychosocial
interventions”, Screen* dementia, Dementia AND (cognitive screening ); Dementia
AND “cognitive screening” AND “screening instrument”; “Dementia Screening” AND(“subjective memory complaints” OR “SMC”); (“mild cognitive impairment” OR “MCI”)
AND (diagnosis OR “assessment); (“mild cognitive impairment” OR “MCI”) AND“Montreal Cognitive Assessment”; dementia AND (“assessment of higher orderfunction” OR “assessment of higher executive function”); dementia AND (“verbal
121

fluency” OR “category fluency”); (dementia” OR “Alzheimers disease” OR AD) AND“measures of progression”; (Dementia” OR “Alzheimers disease” OR AD) AND“severity of dementia”; thyroxine AND dementia; Investigation AND dementia; syphilis
AND dementia; VDRL AND dementia; dementia AND (“serum B12” OR “folate” OR“homocysteine); (“diagnostic classification” OR “diagnostic criteria”) AND (“Alzheimers
disease” OR AD); (“diagnostic classification” OR “diagnostic criteria”) AND (“vasculardementia” OR VAD); (“diagnostic classification” OR “diagnostic criteria”) AND(“Dementia with Lewy Body” OR “Lewy Body Dementia”); (“Diagnostic classification”
OR “diagnostic criteria”) AND (“Parkinson’s Disease Dementia” OR PDD); (“Diagnostic
classification” OR “diagnostic criteria”) AND “Frontal Temporal Dementia”; (“Diagnostic
classification” OR “diagnostic criteria”) AND “Mixed Dementia”; (“Diagnostic
classification” OR “diagnostic criteria”) AND “Mild Cognitive Impairment”; Dementia
AND biomarkers; Biomarkers and DLB; (“Assessment of Depression” OR “Assessmentof mood symptoms”) AND dementia; (“BehaviouralPsychological Symptoms ofdementia” OR “Neuropsychiatric symptoms of dementia”) AND “NeuropsychiatricInventory”; (“Behavior and psychological symptoms of dementia” OR “Neuropsychiatric
symptoms of dementia”) AND “brief psychiatric rating scale”; (“Behavior andpsychological symptoms of dementia” OR “Neuropsychiatric symptoms of dementia”)
AND “BEHAVE-AD”; (Behavior and psychological symptoms of dementia” OR“Neuropsychiatric symptoms of dementia”) AND “Brief Psychiatric rating scales”;“Assessment of functional deficits” AND (dementia OR “Alzheimer disease”);(“Activities of daily Living assessment” OR “ADL assessment”) AND (dementia OR“Alzheimer disease”); dementia AND (“Acetylcholinesterase inhibitors” OR Donepezil
OR Rivastigmine OR Galantamine); Dementia AND (“Acetylcholinesterase inhibitors”
OR Donepezil OR Rivastigmine OR Galantamine) AND (Improvement in cognitive
function OR Cognition); Dementia AND (“NMDA antagonist” OR Memantine) AND(Improvement in cognitive function OR Cognition); Dementia AND (Alternative drugs
OR Codergocrine mesylate OR Ginkgo biloba OR Nicergoline OR Nimodipine OR
Hyergine OR NSAIDS OR Estrogen OR Fish Oils OR Vitamin E OR Vitamin B12 OR
Lecithin OR Folate OR Sage) AND Improvement in cognitive function OR Cognition OR
Memory OR Language OR Orientation OR Concentration OR “Executive function” OR
Learning); “Fatty Acids, Omega-3”[Mesh] AND “Dementia”[Mesh]; dementia AND“Ginkgo biloba”[Mesh];”Lecithins”[Mesh] AND “dementia”; dementia AND “Ergoloid
Mesylates”[Mesh]; dementia AND “Salvia officinalis”[Mesh]; “Dementia”[Mesh] AND“Vitamin E”[Mesh]; “Dementia”[Mesh] AND “Anti-Inflammatory Agents, NonSteroidal”[Mesh]; Dementia/drug therapy [MeSH] AND Non-cognitive; Dementia AND
Drug therapy AND Non-cognitive; Dementia OR AD OR Alzheimers OR Alzheimers
122Disease OR Mild cognitive impairment AND Pharmacotherapy OR Drug therapy;
Dementia [MeSH] AND Antipsychotics AND “Non-cognitive”, Dementia [MeSH] AND
Antipsychotics AND “Non-cognitive”; Dementia AND Antipsychotics AND [BPSD OR
behavioural OR neuropsychiatric]; Dementia [MeSH] AND Anxiolytics Dementia[MeSH] AND Hypnotics; Dementia [MeSH] AND Antidepressants; Dementia [MeSH]
AND “Acetylcholinesterase inhibitors” OR “Memantine”, Dementia [MeSH] AND
Antimanic OR “Mood stabilisers” Dementia [MeSH] AND Selegiline; Dementia [MeSH]
AND Lithium, “Dementia” AND “combination therapy”; Dementia AND “Dual Therapy”;
Dementia AND “Combination treatment”; Dementia AND “Augmentation Therapy”;
Dementia AND Pharmacological AND “Non-Pharmacological therapy”; Dementia AND“Drug and psychosocial interventions”; Dementia AND “Combination treatment”;(Dementia OR “Alzheimers disease” OR Alzheimers OR AD) AND (“strategies forpromoting independence” OR “psychosocial intervention” OR “behaviour intervention”
OR “non pharmacological intervention”); (Dementia OR “Alzheimers disease” OR
Alzheimers OR AD) AND (“Activities of daily living training” OR “cognitive rehabilitation”
OR “cognitive training” OR “cognitive stimulation activities” OR psychologicalintervention” OR “physical activity program” OR “reminiscence therapy” OR “reality
orientation” OR “validation” OR “setting suitable for dementia” OR “social
engagement”); (Dementia OR “Alzheimers disease” OR Alzheimers OR “BPSD” OR“Behavioural and psychological symptoms of dementia” OR “neuropsychiatric
symptoms of dementia”) AND (“Aroma therapy” OR “Multisensory stimulation” OR“Snoezelen therapy” OR “Group psychotherapy” OR “social engagement” OR “Music
therapy” OR “Physical activity program” OR “massage and touch therapy” OR“reminiscence therapy” OR “reality orientation” OR Validation therapy” OR “behaviour
therapy” OR “animal assisted therapy” OR “white noise”); (Dementia OR “Alzheimers
disease” OR Alzheimers) AND (Depression OR “Anxiety) AND (“Psychologicalintervention” OR “non pharmacological intervention” OR “cognitive rehabilitation” OR“cognitive training OR “cognitive stimulation activities” OR “physical activity” OR“reminiscence therapy” OR “reality orientation” OR “validation therapy” OR “social
engagement” OR “art therapy” OR “music therapy” OR ECT OR electroconvulsive);(Dementia OR “Alzheimers disease” OR Alzheimers OR AD) AND (Environment OR“Environmental design” OR “suitable setting” OR “subjective barriers” OR “therapeutic
garden” OR “design of dining areas” OR “bright light therapy”); (“Dementia caregivers”
OR “Alzheimers Disease caregivers” OR “Alzheimers carers” OR “AD caregivers”)
AND (psychoeducation OR “educational interventions” OR “supportive intervention”
OR psychotherapy OR “training of care recipient” OR “multi-component intervention”
OR “staff training”);
123Appendix 2
CLINICAL QUESTIONS
1.

What are the groups of people who are at increased risk of developing dementia?

2.

For people at risk of developing dementia, are there any non-pharmacologicalstrategies to prevent or delay the onset of dementia?

3.

Are there advantages/disadvantages to early identification of dementia?

4.

Is a person with dementia capable of making decisions?

5.

Is truth-telling beneficial for patients with dementia?

6.

Are these interventions (artificial feeding and hydration, pain treatment,
infection treatment, restraints, resuscitation) beneficial for patients with late/severe dementia?

7.

Are these interventions beneficial for patients with late/severe dementia?

8.

What are the roles of memory clinic?

9.

Are assessments of needs helpful to dementia caregivers?

10.

Are interventions for caregivers beneficial?

11.

Is routine cognitive screening for those 60 years and above at the primarycare level useful to detect early dementia?

12.

What are the tools suitable for screening people at risk of dementia at the
primary care level?

13.

When should patients with dementia be referred to a tertiary specialist
service?

14.

What are the brief cognitive tests that can help in the diagnosis of mild
cognitive impairment or early dementia or dementia, at the secondary/tertiarycare level?

15.

How can one determine the progression of dementia?

16.

What relevant investigations are needed to rule out treatable causes ofdementia?
oRoutine blood investigationoThyroid function testsoTests for syphilisoSerum B1, B12oSerum folate and Homocysteine level124

Appendix 2 (cont.)
17.

Are there diagnostic classifications of dementia for different subtypes ofdementia?
o

ICD10

o

DSM-IVo

NINDS- AIREN, ADDTC or HACHINSKI ISCHEMIC SCORE or RosenoModified ScoreoLund- Manchester Criteriao

MCI criteria

18.

Are biomarkers useful in the diagnosis of dementia (AD, VAD, FTD, DLB/PDD)?

19.

How should non-cognitive functions be assessed?

20.

How do you determine the functional difficulties in patients with dementia

21.

What is the role of CT and MRI brain in patient with dementia ?

22.

What is the role of PET /SPECT in the diagnosis of dementia?

23.

What is the role of EEG’s in the diagnosis of Dementia?

24.

For people with dementia do acetyl cholinesterase inhibitors/NMDA antagonist
when compared to placebo cause improvement in cognitive function?

25.

What are the other choices of drugs (other than acethylcholinesterase inhibitors/
memantine that produce benefit or harm compared with an appropriatecomparator?

26.

For people with vascular dementia do drugs (anti-dementia drugs anddrugs that control vascular risk factors) when compared to placebo cause
improvement or decline in cognitive function?

27.

For people with dementia do drug treatment when compared to placebo
cause improvement in non- cognitive function?

28.

In healthy adults, is there any pharmaceutical product in the prevention of dementia?

29.

In patient with dementia, are there any combination treatments for cognitive
and non- cognitive symptoms of dementia which produce benefit or harm?

30.

For patients with dementia are the strategies for promoting independence
produce benefits/harm in the specified outcome?
125

Appendix 2 (cont.)
31.

For people with dementia does cognitive rehabilitation produce benefit or harm?

32.

Do psychosocial/behavioural interventions (aromatherapy, reality orientation,
validation therapy, reminiscence) for management of behaviour/psychologicalsymptoms (BPSD) of dementia patient produce benefit or harm?

33.

For people with dementia what environmental designs are appropriatecompared to standard care?

34.

Are educational interventions useful in the management of people withdementia and their caregivers?

126

Appendix 3
MALAY- MINI MENTAL STATE EXAMINATION
Introduction
Three versions of the Malay-MMSE (M-MMSE) have been validated in a group of
Malay-speaking elderly population in Malaysia [116] Scores lower than the optimal
cut-off scores indicate cognitive impairment. Please refer to the table below for theappropriate cut-off scores for each of the three versions of the M-MMSE based on
the education level and gender.
o

M-MMSE-7 refers to serial 7so

M-MMSE-3 refers to serial 3s instead of serial 7so

M-MMSE-S refers to asking the patient to spell the word ‘dunia’ backwards
instead of serial 7

Table 9. The optimal cut-off scores for the screening of dementia forM-MMSE-7,
M-MMSE -3, M-MMSE-S.
M MMSE-7

M MMSE-3

M MMSE-S

Combined male and female

≤21

≤18

≤17

Male

≤23

≤22

≤19

Female

≤19

≤18

≤18

127

Appendix 3 (cont.)
Malay MMSE Assessment Type: .............................................................................
Patient ID: ..........................................

Date:......................................................

Male oFemale o

Educational level: Primary oSecondary oSex:

Tertiary oMarkahMaximum
pesakit5
Orientasi Masa
Tahun, bulan, hari, tarikh, waktu (+/- 1 jam)
5

Orientasi Tempat
Negara, Negeri, Bandar,Tempat (hospital/rumah), bilik (wad/klinik)

3

Pendaftaran
Saya akan menguji ingatan awak. Sila dengar dengan teliti, tiga objek
yang saya akan baca, iaitu, oren, kunci dan sikat. Sila sebut semula tiga
objek tadi. Ingat betul-betul, kerana saya akan bertanya kemudian.

5

Perhatian dan Pengiraan (sila guna salah satu kaedah)
M-MMSE-7: Sila tolak 7 dari 100 dan teruskan.
M-MMSE -3: Atau, tolak 3 dari 20 dan teruskan.
M-MMSE-S: Atau, ejakan perkataan ‘DUNIA’ dari belakang ke depan.

3

Ingat KembaliSila sebut kembali 3 objek yang telah disebut tadi.

2

Penamaan
Namakan benda ini. (Pensel dan Jam Tangan)

1

Ulangan
Sebutkan ‘Tidak mungkin dan cukup mustahil’

3

Arahan tiga peringkat
Ambil kertas dengan tangan kanan, lipat setengah dan letakkan atas
lantai/meja.

1

PembacaanBaca dan lakukan …..TUTUP MATA ANDA

1

Penulisan
Tulis satu ayat yang lengkap.

1

Penyalinan
Salinkan rajah berikut

Jumlah128

Appendix 4
THE ICD-10 CLASSIFICATION OF MENTAL AND BEHAVIOURAL DISORDERS
DEMENTIA
G1. Evidence of each of the following:
(1)

(2)

G2.

A decline in memory, most evident in the learning of new information.
m

Mild: A degree of memory loss sufficient to interfere with everyday
activities, but still compatible with independent living.

mModerate: A degree of memory loss causing a serious handicap to
independent living. Only highly learned material is retained.

m

Severe: Only fragments of previously learned information
remain. The subject fails to recognize even close relatives.

A decline in other cognitive abilities characterized by deterioration in judgement
and thinking, such as planning and organizing, and in the general processingof information.
m

Mild: Individual is independent but complicated daily tasks orrecreational activities cannot be undertaken.

mModerate: The individual is unable to function without the assistanceof another in daily living.

m

Severe: The decline is characterized by an absence, or virtual absence,of intelligible ideation.

Preserved awareness of the environment
Absence of clouding of consciousness. When there are superimposed
episodes of delirium the diagnosis of dementia should be deferred.

G3.

A decline in emotional control or motivation, or a change in social behaviour,
Manifests as at least one of the following: (1) emotional lability; (2) irritability;(3) apathy; (4) coarsening of social behaviour.

G4.

For a confident clinical diagnosis:

129Appendix 4 (cont.)
G1should have been present for at least six months.
Comments: The diagnosis is further supported by evidence of damage to otherhigher cortical functions, such as aphasia, agnosia, apraxia. Judgment about
independent living or the development of dependence (upon others) needs totake account of the cultural expectation and context.

F00

DEMENTIA IN Alzheimers Disease (for details please refer to ICD 10)
A.

The criterias G1 to G4 must be met.

B.

There is no evidence from the history, physical examination or special
investigations for any other possible cause of dementia.

Comments: The diagnosis is confirmed by post mortem evidence.
Specification of features for possible subtypes:
Because of the possibility that subtypes exist, it is recommended thatthe following characteristics be ascertained as a basis for a further classification:
age at onset; rate of progression; the configuration of the clinical features,
particularly the relative prominence (or lack) of temporal, parietal or frontal lobe
signs; any neuropathological or neurochemical abnormalities, and their pattern.
Subdivision of dementia in Alzheimers disease:
F00.0
Dementia in Alzheimers Disease with early onset
F00.1
Dementia in Alzheimers Disease with late onset
F00.2
Dementia in Alzheimers disease, atypical or mixed type
F00.9
Dementia in Alzheimers disease, unspecified

130

Appendix 5
DSM-IV CLINICAL CRITERIA FOR DIAGNOSIS OF DEMENTIA
Cognitive domain

Questions

Amnesia

Any forgetfulness?
Did it start gradually or suddenly?
Is it progressively worse?
And if so, is it smoothly declining or showing a
step-wise/fluctuating decline?
Is it over short-term or long-term matters?

AND declines in one of the following domains:
Aphasia

Any word-finding difficulty orother difficulties with communication?
Any problems with buttoning or dressing?

Apraxia

Agnosia

Executive
dysfunctioning

Any difficulties with using utensils during meal
times?
Any problems recognising familiar faces orfamiliar items?
Any problems handling money (loose change)?
Any change in general problem solving
abilities?
Is one’s work becoming more disorganised?

OF sufficient severity tocause significant
impairment in social or
occupational functioning

As a result of the above, is the patient becoming
less independent in the- community?
- home-care?
- self-care level?

(Source: American Psychiatric Association [165]. Diagnostic and Statistical Manual of Mental Disorders, 1994 & Singapore
MOH Clinical Practice Guidelines 3/2007)[45],[180]131Appendix 6
290.00 DIAGNOSTIC CRITERIA FOR DEMENTIA OF THE Alzheimers TYPE
(based on DSM- IV TR)A.

The development of multiple cognitive deficits manifested by both:(1)

memory impairment (impaired ability to learn new information or torecall previously learned information)(2)

one (or more) of the following cognitive disturbances:(a)aphasia (language disturbance)(b)apraxia (impaired ability to carry out motor activities despite
intact motor function)(c)agnosia (failure to recognize or identify objects despite intact
sensory function)(d)disturbance in executive functioning (ie, planning, organizing,
sequencing, abstracting).

B.

The cognitive deficits in Criteria A1 and A2 each cause significant impairment
in social or occupational functioning and represent a significant decline froma previous level of functioning.

C.

The course is characterized by gradual onset and continuing cognitive decline.

D.

The cognitive deficits in Criteria A1 and A2 are not due to any of the following:(1)other central nervous system conditions that cause progressive
deficits in memory and cognition (eg, cerebrovascular disease,
Parkinson’s disease, Huntington’s disease, subdural hematoma,
normal-pressure hydrocephalus, brain tumor)(2)

systemic conditions that are known to cause dementia (eg,hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency,
hypercalcaemia, neurosyphilis, HIV infection)(3)

substance-induced conditions.
132

Appendix 6 (cont.)
E.

The deficits do not occur exclusively during the course of a delirium.

F.

The disturbance is not better accounted for by another Axis I disorder(eg, Major Depressive Disorder, Schizophrenia).

Code based on type of onset and predominant features:With Early Onset: if delirium is superimposed on the dementia
290.11

With Delirium: if delirium is superimposed on the dementia

290.12

With Delusions: if delusions are the predominant feature

290.13

With Depressed Mood: if depressed mood (including presentations
that meet full symptom criteria for a Major Depressive Episode) isthe predominant feature.

290.10Uncomplicated: if none of the above predominated in thecurrent clinical presentation. With Late Onset: if onset is afterage 65 years.

290.3

With Delirium: if delirium is superimposed on the dementia

290.20With Delusions: if delusions are the predominant feature

290.21

With Depressed Mood: if depressed mood (including presentations
that meet full symptom criteria for a Major Depressive Episode) isthe predominant feature.

290.00Uncomplicated: if none of the above predominates in the current
clinical presentation

Specify if: With Behavioural DisturbanceCoding note: Also code 331.0 Alzheimers Disease on Axis III(Source: SIGN [63] Guideline 2006)133

Appendix 7
DISCLOSURE OF PROGNOSES AND DIAGNOSESGood practice in the disclosure of prognoses and diagnoses

Giving ‘bad news’•

Use patient-led communication•

Tailor your approach for each individual•

Remember that this is a dynamic and ongoing process•

Identify any potential benefits of knowing the diagnosis•

Instill hope

Diagnosis disclosure-suggested guidelines•

Use a multi-professional approach to answer questions and makerecommendations•

Consider telling patient and caregiver together•

Allow each separate time to talk and ask questions•

Arrange follow-up meetings to continue discussions•

Discuss how the disease might progress•

Agree to a care plan•

Provide written educational materials•

Provide a list of community resources and contacts•

Arrange for further support e.g. supportive individual or group counselling
Adapted from Pinner & Bouman (2003). [330]134Appendix 8
Table 10 : ACETYLCHOLINESTERASE INHIBITORS [270]
Drugs

DosageDonepezil

5 mg od at bedtime,increased after one
month to 10 mg od
Max: 10 mg od

Dosage in renal
failureNo dose adjustment

Rivastigmine

No dose adjustment

In moderate renal impairment,
reduced dose ≤ 16 mg/day.
In severe renal impairment(creatinine clearance < 9 ml/min), galantamine is NOT
recommended
Moderate hepatic impairment(Child-Pugh score of 7 to 9),
total daily dose ≤ 16 mg/day
In severe hepatic impairment(Child-Pugh score of 10 to 15),
it is NOT recommended.

Dosage in hepatic
insufficiency

No dose adjustment

No dose adjustment

Common adverse
eventsGastrointestinal:
Diarrhea, loss ofappetite, nausea,
vomiting
Musculoskeletal:
Cramp
Neurologic: Insomnia
Others: Fatigue

CapsuleGastrointestinal: Nausea, vomiting,diarrhea, loss of appetite, abdominal
pain
Metabolic: Weight loss
Neurologic: Dizziness, headache

Anesthesia withsuccinylcholine
Asthma or obstructive
pulmonary disease
Cardiac conduction
abnormalities (SVT,
AV block)
Concurrent use of
nonsteroidal antiinflammatory drugs(NSAIDs)
Gastrointestinal
disease or history ofulcer disease
Seizure history

Transdermal patch
Gastrointestinal: Diarrhea, nausea,
vomiting
l

l

l

l
l

l

Extrapyramidal symptom,
increased incidence orlintensity of tremorllSeizure history;l

Peptic ulcers orlgastrointestinal bleeding;llAnesthesia withsuccinylcholine
Asthma or obstructive pulmonary

Gastrointestinal: Nausea,
vomiting, diarrhea, loss ofappetite
Endocrine metabolic: Weightloss
Neurologic: Dizziness, headache

diseasel

Precautions

Galantamine

Oral route:
1.5 mg bd, increased to 3 mg BD
by minimum of 2 weeks according
to response and tolerance;
Initially 4 mg bd. Increased to 8
Max: 6 mg bd
mg bd after 4 weeks.
Transdermal/patch:
Initial dose is 4.6 mg once daily
Maintenance 8-12 mg bd
and increased to the 9.5 mg
once daily, after a minimum of 4
weeks according to response andtolerability.

lll

Urinary obstruction
Sick sinus syndrome or othercardiac conduction conditions.

135lAnesthesia withsuccinylcholine
Asthma or obstructive
pulmonary disease
Cardiac conduction
abnormalities (SVT, AV block)
Concurrent use of
nonsteroidal antiinflammatory drugs (NSAIDs)
Gastrointestinal disease or
history of ulcer disease
Seizure history

Appendix 9
TABLE 11: N-METYL-ASPARTATE RECEPTOR ANTAGONIST (MEMANTINE)
Drug

Memantine
Initial dose: 5 mg OD. The dose should be increased in
5 mg increments to 10 milligrams/day ( mg/day) given as
5 mg bd, 15 mg/day given in separate doses of 5 mg and
10 mg, and 20 mg/day given as 10 mg bd.

DosageThe minimum recommended interval between dose
increases is 1 week
The recommended maintenance dose is 10 mg bd
Dosage in renal
failureIf creatinine clearance (CrCl), <30ml/min: dose adjusted to
5 mg bdIf creatinine clearance >30 ml/min: No dose adjustment
required

Dosage in Hepatic
insufficiency

No information

Cardiovascular : Hypertension
Common adverse
Gastrointestinal : Constipation
effects (Commons)
Neurologic: Dizziness, Headache, Painl

Precautions

l

l

l

l

Concomitant use of drugs that make the urine alkaline,
the clearance of memantine was reduced by about 80%
under alkaline urine conditions at pH 8
(eg: Sodium Bicarbonate, Carbonic anhydrase inhibitors(eg: Acetazolamide, methazolamide))concomitant use of other NMDA antagonists
genitourinary conditions that raise urine pH; may
increase plasma levels of memantine
moderate to severe renal impairment.
seizure disorder136

Appendix 10
Table 12 : ANTIPSYCHOTICS
Drug

Risperidone

Olanzapine

Quetiapine

Aripripazole

Starting
dose

0.5 mg daily

2.5 mg12.5 to 50
mg daily

5 mg dailylBlack box
warningl

Maximum
dose

Adverse effects

2 mg daily

Rash, hyperprolactinemia, weight
gain, abdominal pain, constipation,
diarrhea, increased appetite,indigestion, nausea & vomiting,
Extrapyramidal syndrome, including
Parkinsonism, excessive salivation
and akathisia, dizziness, headache,insomnia, somnolence.

10 mg

Chest pain, orthostatic hypotension,
peripheral edema, tachyarrhythmia,
hyperlipidemia, xerostomia
hyperglycemia, increased appetite &weight gain, constipation, indigestion,
Extrapyramidal disease, Parkinsonian
abnormal gait, akathisia, asthenia,
dizziness, somnolence.

200 to 300
mg daily

Orthostatic hypotension, tachycardia
hyperlipidemia, xerostomia, weight
gain, constipation, increased appetite
increased liver enzymes, asthenia,
dizziness, extrapyramidal disease,headache, insomnia, sedated,
somnolence, agitation, fatigue.

15 mg daily

Weight gain, constipation, nausea& vomiting, akathisia, dizziness,extrapyramidal disease, headache,insomnia, sedated, somnolence,tremor, anxiety, restlessness, fatigue.

Elderly patients with dementia-related psychosis treated withatypical antipsychotic drugs are at an increased risk of death;most deaths were attributed to cardiovascular events(e.g. heart failure or sudden death) or infections (e.g. pneumonia)
Cerebrovascular adverse events (stroke, transient ischemic attack)including fatalities, have been reported in elderly patients withdementia-related psychosis.

(Source: MICROMEDEX ® HEALTHCARE SERIES, Vol 141 Version 2009 [270])

137

Appendix 11
Table 13 : AntidepressantsName

Starting

Maximum

RenalfailureHepatic
insufficiency

Adverse Effects

Selective Serotonin Reuptake Inhibitors
Sertraline

25 mg

150 mgNo
Lower or lessadjustment frequent dose

Fluoxetine

20 mg

40 mg

No
Lower or lessadjustment frequent dose

Escitalopram

10 mg

20 mg

Caution insevere RF

Fluvoxamine

25 mg

300 mgLower startNo
dose andadjustment monitor dose
increase

No adjustment

Weight gain,
bloating,
constipation,
xerostomia,
asthenia, dizziness,headache,somnolence,nervousness,blurred vision,
urinary retention,rash, sweating,abnormalejaculation,
reduced libido,orgasm incapacity,
fatigue

Precautions:• Increased risk of developing cardiac abnormalities• Cardiovascular disease - cardiac conduction defects, arrhythmias, congestive heart failure,
myocardial infarction, stroke, tachycardia• Hyponatremia
Serotonin and Noradrenaline Reuptake Inhibitor (SNRIs)

Venlafaxine

37.5 mg

225 mg

Dose
Lower or lessadjustment frequent dose

Nausea, insomnia,
dry mouth,
somnolence,dizziness,sweating,
nervousness,headache, sexual
dysfunction.
Hypertension.

Noradrenergic and specific Serotonergic Antidepressants (NaSSA)

Mirtazepine

15 mg

30 mg

Cautionin renal
failure(Source: MICROMEDEX ® HEALTHCARE SERIES, Vol 141 Version 2009 [270])

138

Monitor dose
increase

Increased
appetite, weight
gain, drowsiness,oedema, dizziness,headache, blood
dyscrasia.
Nausea/sexual
dysfunction
uncommonAppendix 12
Environmental designs appropriate for people with dementia
General RecommendationsA) Institution
Unit size:• Give consideration to the size of units, mix of residents and the skill mix of staff to ensurethat the environment is supportive and therapeutic.
• Smaller units are associated with gains that include less anxiety and depression, greater
mobility, increase in supervision and interaction between caregiver and residents, higher
motor functioning, improve or maintenance of ADL’s and lowers level of strain and better
attitude to dementia care.
Dining:• Food not served in tray and served in a common dining room.
(Modified from NICE guidelines)[13] Level III,good

Other recommendations:• Simulated home environment/show rooms in the hospital/community settings.
• Usual care consists of education materials and booklet describing home environment
safety tips.
• Safety devices (alarms, child proof locks) - No study reports outcome of using thiselectronic devices [282]• Floor with coarse-textured coverings, shining, with sharp colour contrast and highly
patterned surfaces can be misinterpreted as change in level by people with impaired
depth perception.[13}Special recommended featuresB) Domestic setting• When organising living arrangements and/or care homes for PWD, must ensure thatbuilt environment are enabling and aid orientation. Attention should be given to lighting,colour schemes, floor coverings, assistive technology, signage, garden design and theaccess to and safety of the external environment.
• Incorporate outdoor areas with therapeutic design features.
• Using covers over fire exit bars and door knobs helps to reduce unwanted exiting.
• Tactile way finding cues, good lighting and windows allowing daylight to enter, view of
external landmarks may help PWD to find their way around the indoor environment.
• Colors may also used to assist with orientation.
• Highly visible toilets may potentially reduce level of incontinence.
• Providing moderate level of environmental stimulation is also recommended such as
murals on walls.
• Wandering paths are recommended.
(Modified from Singapore guidelines) [45]139Appendix 13
Educational interventions in the management of people withdementia and their caregivers:
Recommendations
1. Both PWD and their caregiver are entitled to receive relevant information regarding
dementia, treatment, available support services, as well as legal, financial and benefits
advice.

This can be done through: Written information•

Individual or group psychoeducatio•Counselling•

Telemedicine services•

Training courses about dementia, services and benefits, communication and problem
solving in the care of people with dementia•

Cognitive Behaviour Therapy•

Stress management•

Peer support groups tailored to the needs of individuals depending on the stage of
dementia by telephone and through internet•

Involvement of other family members as well as the primary caregiver in family
meetings

2. Components of psychoeducation:•

Disease information, diagnosis, investigations and treatment•

Medication used -efficacy and side effects•

Strategies to improve independence•

Medico-legal issues including driving and finance•Communication skills•

Stress management•

Grief work
(Modified from NICE[13] and SIGN[63])140Appendix 14
WHO PAIN LADDER
WHO three-step “ladder”
If pain occurs, there should be prompt oral administration of drugs in the following
order: nonopioids (aspirin and paracetamol); then, as necessary, mild opioids(codeine); then strong opioids such as morphine, until the patient is free of pain. To
calm fears and anxiety, additional drugs -“adjuvants” -hould be used. To maintainfreedom from pain, drugs should be given “by the clock”, that is every 3-6 hours,
rather than “on demand” This three-step approach of administering the right drugin the right dose at the right time is inexpensive and 80-90% effective. Surgicalintervention on appropriate nerves may provide further pain relief if drugs are notwholly effective.

World Health Organization Analgesic Ladder

Source: http://www. Painstop.com.au/gallery/images/underst.

141

ABBREVIATIONS
AChEIAcetylcholinesterase inhibitors

AD

Alzheimer disease

ADAS-Cog

Alzheimer Disease Assessment Scale- Cognitive

ADL

Activities of daily living

ADAS-Cog

Alzheimer disease Assessment Scale-Cognition

ADCS-ADL

Alzheimers Disease Cooperative Study–Activities of Daily Living

AUC

Area Under The Curve

AβPP

amyloid β-protein precursor

BADL

Basic activities of daily living

BEHAVE-AD

Behavioural Pathology in AD Rating Scale

BPRS

Brief Psychiatric Rating Scales

BPSD

Behavioural and psychological symptoms of dementia

CADASIL

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts andLeucoencephalopathy

CBT

Cognitive Behaviour Therapy

CDR

Clinical Dementia Rating

CDR-SB/CDR-SOB Sum Boxes of Clinical Dementia Rating Scale
CPR

Cardio-Pulmonary Resuscitation

CGIC

Clinical Global Impression of Change

CGI scaleClinical Global Impression scale

CGI-I

Clinical Global Impression of Improvement

CGI-S

Clinical Global Impression of Severity

CJD

Creutzfeldt-Jakob diseaseCI

Confidence Interval

CMAI

Cohen Mansfield Agitation Inventory

CNS

Central Nervous System

CSF

Cerebrospinal fluid

CSDD

Cornell Scale for Depression in Dementia

CT

Computed tomography

CVFT

Categorical Verbal Fluency Test

DAD

Disability Assessment for Dementia

DLB

Dementia with Lewy bodies

DSM-IV-TR
ECAQ

Diagnostic statistical manual, 4th edition, revised version
Elderly Cognitive Assessment Questionnaire

EEG

Electroencephalography

FBI

Frontal Battery instrument

FTLD

Frontotemporal lobar degeneration

FTD

Frontotemporal dementia

GDS

Geriatric Depression ScaleHR

Hazard ratio

142

IADL

Instrumental Activities Of Daily Living

ICD-10International Classification Diagnostic manual, version 10

ITT-LOCF

Intention to treat - last observation carried forward

IQCODE

Questionnaire on Cognitive Decline in the ElderlyLRlikelihood ratio

LOCF

Last Observation Carried Forward

MCI

Mild Cognitive Impairment

MMSE

Mini Mental State Examination

MRI

Magnetic Resonance Imaging

MADRS

Montgomery-Asberg Depression Rating Scale

MoCA

Montreal Cognitive Assessment

NPV

negative predictive value

NMDA

N-methyl-D-aspartate

NNH

Number Needed To Harm

NNT

Number Needed To Treat

NFTs

neurofibrillary tangles

NPI

Neuropsychiatric Inventory

NPs

Neuritic plaques

NSAIDs

Non-steroidal anti-inflammatory drugs

OAS

Observed Affect ScaleOC

Observation carried forward

OMR

Overall Misclassification RateOR

Odds Ratio

PET

Positron Emission Tomography

PDD

Parkinson Disease Dementia

PIB

Pittsburgh Compound B

PPV

Positive predictive value

PWD

People with dementia

RCT

Randomised Controlled Trial

ROT

Reality Orientation Therapy

RR

Relative riskSD

Semantic Dementia

SIB

Severe Impairment Battery

SPECT

Single Photon Emission Controlled Tomography

SDS

Symptoms of Dementia Screener

SMC

Subjective Memory Complaint

SSRI

Selective Serotonin Reuptake Inhibitor

Sn

Sensitivity

Sp

Specificity

TCAs

Tricycyclic antidepressants

VaD

Vascular Dementia

WMS

Weschler Memory Scale143

ACKNOWLEDGEMENT
The committee of this guideline would like to express their gratitude andappreciation to the following for their contributions:oPanel of external reviewers who reviewed the draft formoTechnical Advisory Committee for Clinical Practice Guidelines for their valuable
input and feedback.

DISCLOSURE STATEMENT
The panel members have no potential conflict of interest to disclose. None holdshares in pharmaceutical firms or acts as consultants to such firms (Details areavailable upon request from the CPG Secretariat).

SOURCES OF FUNDING
The development of the CPG on Management of Dementia (2nd edition) was
supported financially in its entirety by the Ministry of Health Malaysia and wasdeveloped without any involvement of the pharmaceutical industry.

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