Chapter 1
Overview of Dementia: Epidemiology,
Definitions, Terms

CQ 1-1

What are the diagnostic criteria for dementia?
AnswerRepresentative diagnostic criteria for dementia include the International Statistical Classification of Diseases andRelated Health Problems, Tenth Revision (ICD-10) published by the World Health Organization, the diagnostic criteria
proposed by the National Institute on Aging–Alzheimer’s Association Workgroup (NIA-AA), and Diagnosis andStatistical Manual of Mental Disorders, Fifth Edition (DSM-5) published by the American Psychiatric Association.

Comments and evidence
In ICD-10 (1993), dementia is described as “a syndrome due to disease of the brain, usually of a chronic or progressive
nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation,
comprehension, calculation, learning capacity, language, and judgement”. Detailed diagnostic criteria are provided in
ICD-10 1).
In the diagnostic criteria of dementia proposed by the NIA-AA (2011), impaired ability to acquire or remember new
information, impaired executive function, impaired visuospatial abilities, and impaired language functions are treatedequally, and the diagnostic criteria include behavioral impairment and subtypes of dementia other than Alzheimer’s disease
dementia 2).
DSM-5 (2013) introduced a new term, “neurocognitive disorders”, and replaces the term “dementia” with “major
neurocognitive disorder”. DSM-5 details six cognitive domains that may be affected in neurocognitive disorders. A diagnosis
of major neurocognitive disorder (dementia) requires evidence of significant decline in one or more of the following cognitive
domains: complex attention, executive function, learning and memory, language, perceptual-motor function, and social
cognition, and that the cognitive deficits interfere with independence in activities of daily living 3). DSM-5 provides new
information sources for these criteria.

▪ References
1) World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 10th Revision. Geneva: World HealthOrganization; 1993.
2) McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National
Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7(3): 263-269.
3) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: DSM-5. Arlington, VA: American
Psychiatric Association; 2013.

▪ Search formula
PubMed search: July 3, 2015 (Friday), August 8, 2015 (Friday)#1 ((“Dementia/diagnosis” [Majr] OR “Dementia/classification” [Majr] OR dementia [TI]) AND (definition* [TIAB] OR criteria [TIAB] OR
concept* [TIAB])) OR ((“Cognition Disorders/diagnosis” [Majr] OR “Cognition Disorders/classification” [Majr] OR cognition disorder* [TI] OR“cognitive dysfunction” [TI]) AND (definition* [TIAB] OR criteria [TIAB] OR concept* [TIAB]))
Ichushi search: July 3, 2015 (Friday)#1 (Dementia/MTH OR Dementia/TI OR Cognitive disorder/MTH OR Cognitive disorder /TI) AND ((((SH = Diagnostic use, diagnosis,
diagnostic imaging, X ray diagnosis, radionucleotide diagnosis, ultrasound diagnosis) OR Diagnosis/TH OR Diagnosis/TI) AND (Definition/TI
OR Criteria/TI)) OR (Term/TI OR Synonym/TI OR Synonym/TI OR Synonym/TI OR Disease name/TI OR Name/TI OR History/TI OR
Origin/TI))

2

Clinical Practice Guideline for Dementia 2017

CQ 1-2

What other terms are related to dementia?
Answer
The DSM-5 introduces the new terms of major neurocognitive disorder (replacing dementia) and mild neurocognitive
disorder (replacing mild cognitive impairment or MCI). Other terms include subjective cognitive impairment (SCI) andsubjective cognitive decline (SCD).

Comments and evidence
The National Institute on Aging–Alzheimer’s Association (NIA-AA) workgroup classifies Alzheimer’s disease into threedisease stages based on the pathophysiological process of Alzheimer’s disease: preclinical Alzheimer’s disease 1), mild cognitive
impairment (MCI) due to Alzheimer’s disease 2), and dementia due to Alzheimer’s disease (Alzheimer’s disease dementia) 3).
In addition, the preclinical stage is divided into stage 1 (asymptomatic amyloidosis), stage 2 (amyloidosis + neurodegeneration),and stage 3 (amyloidosis + neurodegeneration + subtle cognitive decline).
In DSM-5 (2013), the new term “neurocognitive disorders” was introduced. Neurocognitive disorders are classified intodelirium, major neurocognitive disorder, and mild neurocognitive disorder. DSM-5 details the diagnostic criteria for thesethree types 4).
Vascular cognitive impairment (VCI) is a concept that comprehensively encompasses a range of cognitive deficits frommild cognitive impairment caused by cerebrovascular disorder to vascular dementia (VaD) 5). Vascular cognitive disorder(VCD) has been proposed as a diagnostic category that includes VCI, post-stroke dementia, genetic VaD [cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cerebral autosomal recessive
arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), Binswanger disease, and Alzheimer’s disease
with VaD 6). (See CQ14-1).
Multiple definitions have been proposed for mild cognitive impairment, and the concept has undergone changes. Apartfrom the diagnostic criteria proposed by Peterson et al. 7) in 2004, diagnostic criteria have been provided in DSM-5, NIA-AA
and ICD-10 8), all of which differ to some extent (see CQ4B-5). In addition to mild cognitive impairment, other conditions
such as age-associated memory impairment (AAMI), aging-associated cognitive decline (AACD), mild cognitive disorder(MCD), mild neurocognitive decline (MNCD), and cognitive impairment no dementia (CIND) have been included in theconcept of prodromal stage of dementia9).

▪ References
1) Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National
Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7(3): 280-292.
2) Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the
National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7(3):270-279.
3) McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National
Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7(3): 263-269.
4) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: DSM-5. Arlington, VA: American
Psychiatric Association; 2013.
5) Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive
impairment harmonization standards. Stroke. 2006; 37(9): 2220-2241.
6) Roman GC, Sachdev P, Royall DR, et al. Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment andvascular dementia. J Neurol Sci. 2004; 226(1-2): 81-87.
7) Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3): 183-194.
8) World Health Organization. International Statistical Classification of Diseases and Related Health problems. 10th Revision. Geneva: World HealthOrganization; 1993.
9) “Treatment Guideline for Dementia” Preparation Joint Committee (Ed.) Japanese Society of Neurology (Supervision). Treatment Guideline for
Dementia 2010. Tokyo: Igaku Shoin; 2010. (In Japanese)

Chapter 1

3▪ Search formula
PubMed search: July 3, 2015 (Friday), August 8, 2015 (Friday)#1 ((“Dementia/diagnosis” [Majr] OR “Dementia/classification” [Majr] OR dementia [TI]) AND (definition* [TIAB] OR criteria [TIAB] OR
concept* [TIAB])) OR ((“Cognition Disorders/diagnosis” [Majr] OR “Cognition Disorders/classification” [Majr] OR cognition disorder* [TI] OR“cognitive dysfunction” [TI]) AND (definition* [TIAB] OR criteria [TIAB] OR concept* [TIAB]))
Ichushi search: July 3, 2015 (Friday)#1 (Dementia/MTH OR Dementia/TI OR Cognition disorder/MTH OR Cognition disorder /TI) AND ((((SH = Diagnostic use, diagnosis,
diagnostic imaging, X ray diagnosis, radionucleotide diagnosis, ultrasound diagnosis) OR Diagnosis/TH OR Diagnosis/TI) AND (Definition/TI
OR Criteria/TI)) OR (Term/TI OR Synonym/TI OR Synonym/TI OR Synonym/TI OR Disease name/TI OR Name/TI OR History/TI OR
Origin/TI))

4

Clinical Practice Guideline for Dementia 2017

CQ 1-3What are the causes of dementia and how are they classified?
AnswerDementia is caused by a variety of diseases and conditions. In DSM-5, the etiological subtypes of major neurocognitive
disorder (dementia) comprise Alzheimer’s disease, frontotemporal lobar degeneration, Lewy body disease, vascular disease,
traumatic brain injury, substance/drug use, HIV infection, prion disease, Parkinson’s disease, Huntington’s disease, othermedical conditions, multiple etiologies, and unspecified.

Comments and evidence
Many diseases and conditions may cause dementia or dementia-like symptoms 1).
ICD-10 classifies dementia into Alzheimer’s disease dementia, vascular dementia, dementia in other diseases classified
elsewhere, and unspecified dementia 2).
In the neurocognitive disorder category of DSM-5, the etiological subtypes of major neurocognitive disorder (dementia)
and minor neurocognitive disorder (mild cognitive impairment) are listed as follows: Alzheimer’s disease, frontotemporallobar degeneration, Lewy body disease, vascular disease, traumatic brain injury, substance/drug use, HIV infection, priondisease, Parkinson’s disease, Huntington’s disease, other medical conditions, multiple etiologies, and unspecified 3).
Among these causative diseases and conditions, some neurosurgical diseases such as normal pressure hydrocephalus andchronic subdural hematoma, as well as some medical diseases such as hypothyroidism and vitamin B12 deficiency are being
treated under the concept of treatable dementia, and early diagnosis and appropriate treatments and interventions aredesirable.

▪ References
1) “Treatment Guideline for Dementia” Preparation Joint Committee (Ed.) Japanese Society of Neurology (Supervision). Treatment Guideline for
Dementia 2010. Tokyo: Igaku Shoin; 2010: 4-7. (In Japanese)
2) World Health Organization. International Statistical Classification of Diseases and Related Health problems. 10th Revision. Geneva: World HealthOrganization; 1993.
3) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: DSM-5. Arlington, VA: American
Psychiatric Association; 2013.

▪ Search formula
PubMed search: July 3, 2015 (Friday)#1 (“Dementia/etiology” [Majr] OR (dementia [TI] AND etiology) OR “Cognition Disorders/etiology” [Majr] OR ((cognition disorder* [TI] OR“cognitive dysfunction” [TI]) AND etiology)) AND (“Risk Factors” [Majr] OR risk factor* [TI])
Ichushi search: July 3, 2015 (Friday)#1 (Dementia/MTH OR Dementia /TI OR Cognitive impairment/MTH OR Cognitive impairment /TI) AND ((SH = Etiology) OR Etiology/TI
or Cause/TI) AND ((Risk factor/TH OR Risk factor /TI OR Risk/TI) AND (PT = Review)) OR ((SH = Etiology) AND (Etiology /TI OR Cause/
TI))

Chapter 1

5

CQ 1-4

What pathological conditions should be differentiated from dementia?
AnswerPathological conditions that should be differentiated from dementia, especially Alzheimer’s disease dementia, include
normal cognitive decline accompanying aging (physiological amnesia), delirium, depression, other learning disabilities,
and mental retardation.

Comments and evidence
DSM-5 lists pathological conditions that should be differentiated from dementia as follows: normal cognitive decline
accompanying aging, delirium, depression, other learning disabilities, and mental retardation 1). Important points fordifferentiation of Alzheimer’s disease dementia from the above disorders are summarized below.

1. Physiological amnesia accompanying aging
In general, physiological amnesia is differentiated from dementia by partial forgetfulness of past experience, with no or
slow progression, preserved self-recognition of the disability, preserved orientation to time, and little disturbance in activities
of daily living.

2. Delirium
Delirium is an acute psychiatric symptom accompanied by impaired consciousness, causing difficulties to focus andmaintain attention. Common triggering factors include physical illnesses, environmental changes, and effects of drug. The
symptoms fluctuate, which differ from symptom persistence in dementia, but delirium and dementia are often foundconcomitantly.

3. Depression
Pseudodementia due to depression or a depressive state may cause psychomotor retardation and difficulties in concentration,
as well as memory decline and impaired judgement. Patients complain of reduced memorizing ability, which may be mistaken
as dementia. Unlike Alzheimer’s disease dementia, memory and executive dysfunctions usually do not persist in
pseudodementia, and patients often over-estimate their functional impairment (while dementia patients underestimate theirfunctional impairment, reflecting decreased awareness of disease). Response to antidepressants is another point ofdifferentiation.

▪ Reference1) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: DSM-5. Arlington, VA: American
Psychiatric Association; 2013.

▪ Search formula
PubMed search: July 3, 2015 (Friday)#1 (“Dementia/diagnosis” [Majr] OR (dementia [TI] AND (diagnosis OR diagnostic)) OR “Cognition Disorders/diagnosis” [Majr] OR ((cognition
disorder* [TI] OR “cognitive dysfunction” [TI]) AND (diagnosis OR diagnostic))) AND (“Diagnosis, Differential” [Majr] OR “Diagnostic Errors”[Mesh] OR “differential diagnosis” [TI] OR diagnostic error* [TI] OR misdiagnosis [TI])
Ichushi search: July 3, 2015 (Friday)#1 (Dementia/MTH OR Dementia/TI OR Cognitive disorder/MTH OR Cognitive disorder /TI) AND ((((SH = Diagnostic use, diagnosis,
diagnostic imaging, X ray diagnosis, radionucleotide diagnosis, ultrasound diagnosis) OR Diagnosis/TH OR Diagnosis/TI) AND differential
diagnosis/MTH OR differentiation/TI OR misdiagnosis/MTH OR misdiagnosis/TI OR distinction/TI)

6

Clinical Practice Guideline for Dementia 2017

CQ 1-5

What is the prevalence of dementia in Japan?
AnswerIn the first half of the 2010s, the prevalence of dementia in older people aged 65 years and above in Japan was estimatedto be approximately 15%.
A

Comments and evidence
During the period from the 1980s to the 2000s, the prevalence of dementia in older people aged 65 years and above inJapan was reported to be 3.8-11%, and the prevalence of dementia has shown a tendency of increase 1). A survey on theprevalence of dementia in 8 municipalities nationwide estimated that there were 4.26 million older people with dementia in
2012, and the prevalence was reported to be about 15% 2, 3). Based on a longitudinal survey conducted in Hisayama Town,
Fukuoka Prefecture, the future prevalence of dementia was estimated and reported. Assuming that the prevalence of
dementia in each age group remains constant after 2012, the number of people with dementia in 2025 is estimated to be 6.75
million [95% confidence interval (CI); 5.41 million to 8.44 million]. When assuming that the frequency of diabetes increases
by 20% in the future, the number of people with dementia in 2025 is estimated to be 7.3 million (95% CI: 5.7 million to
9.36 million) 4).
The number of people with dementia in the world is estimated to be 46.8 million in 2015, and predicted to increase at apace of doubling every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050. Furthermore, the increase in lowto middle-income countries is predicted to be markedly higher compared to high-income countries 5). On the other hand, a
study in the UK has reported decrease in prevalence of dementia 6), while studies in the Netherlands, Germany, Sweden and
US have reported decreases in incidence of dementia 7-10).

▪ References
1) Dodge HH, Buracchio TJ, Fisher GG, et al. Trends in the prevalence of dementia in Japan. Int J Alzheimers Dis. 2012; 2012: 956354.
2) Ikejima C, Hisanaga A, Meguro K, et al. Multicentre population-based dementia prevalence survey in Japan: a preliminary report. Psychogeriatrics.
2012; 12(2): 120-123.
3) Ministry of Health, Welfare and Labour Grant-in-aid for Dementia Control Integrated Research Project. Prevalence of dementia in urban areas andmeasures for impaired daily living functions in dementia. General Study Report for 2011-2012; 2013. (In Japanese)4) Ministry of Health, Welfare and Labour Grant-in-aid for Dementia Control Integrated Research Project. Study of prediction of future elderly
population with dementia in Japan. General and Partial Study report for 2014. Study Group for Prediction of Future Elderly Population with
Dementia In Japan; 2015. (In Japanese)5) Alzheimer’s Disease International. World Alzheimer Report 2015: The Global Impact of Dementia: an analysis of prevalence, incidence, cost andtrends. London: Alzheimer’s Disease International; 2015.
6) Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from threegeographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013; 382(9902): 1405-1412.
7) Qiu C, von Strauss E, Backman L, et al. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden.
Neurology. 2013; 80(20): 1888-1894.
8) Schrijvers EM, Verhaaren BF, Koudstaal PJ, et al. Is dementia incidence declining?: Trends in dementia incidence since 1990 in the Rotterdam
Study. Neurology. 2012; 78(19): 1456-1463.
9) Doblhammer G, Fink A, Fritze T. Short-term trends in dementia prevalence in Germany between the years 2007 and 2009. Alzheimers Dement.
2015; 11(3): 291-299.
10) Satizabal CL, Beiser A, Chene G, et al. Temporal trends in dementia incidence in the Framingham Study. 2014 Jul 17; Copenhagen: AAIC; 2014.

▪ Search formula
Search formula: search period
PubMed search: May 28, 2015 (Thursday), October 19, 2015 (Thursday)#1 (“Dementia/epidemiology” [Majr] OR dementia [TI]) AND (“Morbidity” [Mesh] OR morbidity [TI] OR incidence [TI] OR prevalence [TI])
Ichushi search: May 28, 2015 (Thursday)#1 (Dementia/TH OR Dementia/TI) AND (Japan/TH OR Japan/TI OR This country/TI) AND (Incidence/TH OR Prevalence/TI OR Incidence/
TI OR Prevalence/TI)

Chapter 1

7

CQ 1-6

Are there changes in prevalence depending on subtype of dementia?
AnswerDementia shows a tendency of increase in Japan, and Alzheimer’s disease dementia is increasing compared to vasculardementia.
B

Comments and evidence
According to a nationwide survey conducted in the first half of the 2010s, the frequency of Alzheimer’s disease dementia
was the highest at 67.6%, followed by vascular dementia at 19.5%, and dementia with Lewy bodies /dementia with Parkinson’s
disease at 4.3% 1). In the 1980s, vascular dementia was more prevalent than Alzheimer’s disease dementia in Japan, but
Alzheimer’s disease dementia has shown a trend of increase since the latter half of the 1990s, especially in older people aged
80 years and above 2-5)

▪ References
1) Ministry of Health, Welfare and Labour Grant-in-aid for Dementia Control Integrated Research Project. Prevalence of dementia in urban areas andmeasures for impaired daily living functions in dementia. General Study Report for 2011-2012; 2013. (In Japanese)
2) Dodge HH, Buracchio TJ, Fisher GG, et al. Trends in the prevalence of dementia in Japan. Int J Alzheimers Dis. 2012; 2012: 956354.
3) Wakutani Y, Kusumi M, Wada K, et al. Longitudinal changes in the prevalence of dementia in a Japanese rural area. Psychogeriatrics. 2007; 7(4):150-154.
4) Sekita A, Ninomiya T, Tanizaki Y, et al. Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese community: the Hisayama
Study. Acta Psychiatr Scand. 2010; 122(4): 319-325.
5) Suzuki M, Fukuda T, Narusei Y, et al. Prevalence over time of dementia viewed from a survey on senile dementia in Toyama Prefecture. Japanese
Journal of Geriatric Psychiatry (Ronen Seishin Igaku Zasshi) 2003; 14(12): 1509-1518. (In Japanese)▪ Search formula
PubMed search: May 28, 2015 (Thursday)#1 (“Dementia/epidemiology” [Majr] OR dementia [TI]) AND (“Morbidity” [Mesh] OR morbidity [TI] OR incidence [TI] OR prevalence [TI])
AND (subtype [TI] OR subtypes [TI] OR “sub type” [TI] OR “sub types” [TI])
Ichushi search: May 28, 2015 (Thursday)#1 (Dementia/TH OR Dementia/TI) AND (Incidence/TH OR Incidence/TI OR Prevalence/TI OR Frequency/TI) AND Disease type/AL

8

Clinical Practice Guideline for Dementia 2017

CQ 1-7Is the disease duration of dementia getting longer?
AnswerStudies have reported a possibility that the survival period of people with dementia may be prolonged. However,there is no report showing that the death rate of people with dementia is clearly lower compared to the general population.
C

Comments and evidence
In the United States, the hazard ratio (HR) for death in people with dementia aged 70 years and above compared to those
without dementia was 2.53 in 1993 and 3.11 in 2002, with no significant change during the 9-year period (p = 0.09) 1). In a
study conducted in Stockholm, Sweden, the mortality rate of people with dementia decreased by 29% over the 14-year
period from 1988 to 2002, but the HR compared to non-dementia subjects was 2.42 in 1988 and 2.47 in 2002, with nosignificant change during the 14 years 2). In these reports, while the incidence of dementia has declined, prevalence has notchanged, suggesting that the duration of dementia may be prolonged 1, 2). In a study using medical insurance claim data in
Germany, the death rate of people with dementia increased by 1% in men (p = 0.75) and 11% in women (P < 0.001) over a
3-year period from 2004 to 2007 3).
When the mean loss of life expectancy (%) (survival period from dementia onset to the mean age of death divided by themean life expectancy of the general population at the age of dementia onset) was analyzed by period, many reports show thatloss of life expectancy in people with dementia decreases after mid-1990s when compared to that from the 1980s to early
1990s 4).

▪ References
1) Langa KM, Larson EB, Karlawish JH, et al. Trends in the prevalence and mortality of cognitive impairment in the United States: is there evidenceof a compression of cognitive morbidity? Alzheimers Dement. 2008; 4(2): 134-144.
2) Qiu C, von Strauss E, Backman L, et al. Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden.
Neurology. 2013; 80(20): 1888-1894.
3) Doblhammer G, Fink A, Fritze T. Short-term trends in dementia prevalence in Germany between the years 2007 and 2009. Alzheimers Dement.
2015; 11(3): 291-299.
4) Brodaty H, Seeher K, Gibson L. Dementia time to death: a systematic literature review on survival time and years of life lost in people withdementia. Int Psychogeriatr. 2012; 24(7): 1034-1045.

▪ Search formula
PubMed search: October 19, 2015 (Thursday)#1 (“Dementia/mortality” [Majr] OR “Cognition Disorders/mortality” [Majr] OR “Dementia/epidemiology” [Majr] OR “Cognition Disorders/
epidemiology” [Majr]) AND ((“Mortality” [Mesh] OR mortality [TIAB] OR survival [TIAB]) AND (“Morbidity” [Mesh] OR “Life Expectancy”[Mesh] OR “morbidity” [TI] OR “incidence” [TI] OR “prevalence” [TI] OR “disease duration” [TI])) OR (“dementia” [TI] AND (“morbidity”[TI] OR “incidence” [TI] OR “prevalence” [TI]))
Ichushi search: October 19, 2015 (Thursday)#1 (Dementia/MTH OR Dementia/TI OR Cognitive Disorders/MTH OR Cognitive Disorders/TI) AND (Disease duration/TI OR Incidence/TH
OR Prevalence/TI OR Frequency/TI OR Survival period/TH OR Mortality/TH OR Survival period/TI OR Mortality/TI OR Survival rate/TI)

Chapter 1

9CQ 1-8What is the pathological background of dementia?
AnswerVarious underlying pathologies are associated with dementia, such as degenerative disease, cerebrovascular disorder,
infection, inflammation, and tumor, and the clinical picture is strongly influenced by the lesion distribution. The frequency
of degenerative diseases is high, and in the majority of these cases, abnormal protein accumulation is the core feature of
the pathology.

Comments and evidence

Alzheimer’s disease is characterized by the formation of large numbers of senile plaques [amyloid β (Aβ) plaque formation]and neurofibrillary tangles (fibrous aggregates of tau protein). Both senile plaques and neurofibrillary tangles also appear inolder people without dementia, but they are particularly abundant in Alzheimer’s disease. It remains unclear how theformation of senile plaques and neurofibrillary tangles leads to neuronal degeneration and loss. The main lesion of dementia
with Lewy bodies is abnormal accumulation of α-synuclein in neurons. In Parkinson’s disease, Lewy lesions are confined tothe brain stem, whereas in dementia with Lewy bodies, Lewy lesions spread to the cerebrum. Alzheimer’s lesions are observedin many patients with dementia with Lewy bodies 1).
Fronto-temporal lobar degeneration (FTLD) is broadly divided into a disease group showing tau accumulation and agroup showing TDP-43 accumulation, while there are rare cases of fused in sarcoma (FUS) protein accumulation 2). Although
there is not always a good correlation between clinical features and pathological diagnosis, many cases of semantic dementia
and cases with coexisting motor neuron disease are associated with TDP-43 accumulation. In Japan, familial FTLD is oftencaused by tau gene mutations.
Argyrophilic grain dementia showing granular accumulation of tau inside neurites, and primary age-related tauopathy(PART) showing abundant neurofibrillary tangles (similar to Alzheimer’s disease) localized to the hippocampal limbic
system but no significant Aβ accumulation are increasingly common in older people aged 80-90 years and above 3).
Hippocampal sclerosis is a general term for disease conditions showing severe neuronal loss and gliosis in hippocampal CA1
and subiculum, with diverse underlying diseases.
Vascular dementia is frequently caused by ischemic brain lesions, and the culprit vascular lesions are broadly classified into
those caused by macrovascular atherosclerosis and those caused by microvascular lesions. Microvascular lesions cause
multiple lacunar infarcts and white matter lesions, and are strongly associated with dementia 4). Amyloid angiopathy also
causes dementia, and in this case is often accompanied by Alzheimer’s lesions. The coexistence of Alzheimer’s lesion andvascular lesion is not simply comorbidity, but is thought to influence each other in pathological mechanisms (see CQ14-4).

▪ References
1) McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.
Neurology. 2005; 65(12): 1863-1872.
2) Mackenzie IR, Neumann M, Bigio EH, et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an
update. Acta Neuropathol. 2010; 119(1): 1-4.
3) Crary JF, Trojanowski JQ, Schneider JA, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta
Neuropathol. 2014; 128(6): 755-766.
4) Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol. 2015; 11(3): 157-165.

▪ Search formula
PubMed search: July 24, 2015 (Friday)#1 ((“Dementia/pathology” [Majr] OR (dementia [TI] AND (pathology* [TI] OR neuropathology*[TI]))) AND (“Brain/pathology” [Majr] OR“Parkinson Disease/pathology” [Majr] OR “Inclusion Bodies/metabolism” [Mesh]) AND (neuropathologic [TI] OR neuropathological [TI] OR
pathologic [TI])) OR ((“Frontotemporal Lobar Degeneration/pathology” [Mesh] OR “Lewy Body Disease/pathology” [Mesh] OR “Alzheimer
Disease/pathology” [Majr] OR (Alzheimer* [TI] AND (pathology* OR neuropathology*))) AND (“Brain/pathology” [Mesh] OR “Parkinson
Disease/pathology” [Mesh] OR “primary age-related tauopathy” [TIAB] OR PART [TI]) AND (“pathological feature” [TIAB] OR “pathologicalprocess” [TIAB] OR “pathologic process” [TIAB] OR “neuropathological criteria” [TIAB] OR neuropathological stage* [TIAB] OR pathogenic
mechanism* [TIAB])) OR ((“Frontotemporal Lobar Degeneration/classification” [Majr] OR “Lewy Body Disease/physiopathology” [Majr] OR(“Tauopathies/pathology” [Majr] AND “Aging/pathology” [Majr]) OR (“Athletic Injuries/pathology” [Majr] AND Cognition [Mesh])) AND

10

Clinical Practice Guideline for Dementia 2017

(“Brain/pathology” [Majr] OR “Inclusion Bodies/metabolism” [Mesh]) AND (neuropathology* [TI] OR pathology* [TI] OR “pathologic
assessment” [TIAB]))
Ichushi search: July 24, 2015 (Friday)#1(Dementia/TH OR Dementia/TI OR Alzheimer/TI OR Fronto-temporal lobar degeneration/TI OR Lewy body/TI) AND (Brain/TH OR
Brain/TI OR Parkinson disease/TH OR Parkinson/TI) AND (((SH = Pathology) OR Pathology/TH) AND Pathology /TI AND (Background/TI
OR Dementia/TI OR Alzheimer/TI OR Fronto-temporal lobe/TI OR Lewy body/TI))

Chapter 1

11