China Cognition and Aging Study: a Multi-center, National-wide, Longitudinal Study in China
Conditions: Mild Cognitive Impairment(MCI), Alzheimer Disease, Late Onset, Familial Alzheimer Disease (FAD), Vascular Dementia (VaD), Normal Control, Non-Alzheimer Degenerative Dementia
Sponsor: Capital Medical University

1 
 
China Cognition and Aging Study 
(China COAST) 
Research protocol updated in 2020 
 
 
 
 
 
Leading Center: Xuanwu Hospital, Capital Medical University 
Principle Investigator: Professor Jianping Jia 
 
 
 
 
 
Ethical Committee Approval Time: 2007, 2012, 2018, 2020 
Version number: 1.4 
International Research Protocol Registration Number: SYXWJ001 
ClinicalTrials.gov ID: NCT03653156 
Time: 2008, 2012, 2018, 2020 
June 30, 2020 
 
 

2 
 
Contents                                                 
1. Study glossary ................................................................................................................................................................... 4 
2. Introduction ...................................................................................................................................................................... 5 
2.1 Background and significance........................................................................................................................................ 5 
2.2 Specific aims................................................................................................................................................................. 7 
3. Study design ...................................................................................................................................................................... 8 
3.1 Research content ......................................................................................................................................................... 8 
3.2 Research methods ....................................................................................................................................................... 9 
3.2.1 Inclusion and exclusion criteria: .......................................................................................................................... 10 
(1) MCI and its subtypes ............................................................................................................................................................. 10 
(2) Sporadic Alzheimer’s disease (SAD) ....................................................................................................................................... 11 
(3) Familial Alzheimer’s disease (FAD) ........................................................................................................................................ 11 
(4) Vascular dementia (VaD) ....................................................................................................................................................... 12 
(5) Normal control ...................................................................................................................................................................... 12 
3.2.2 Subject interview ................................................................................................................................................ 13 
(1) Baseline and follow-up interview items ................................................................................................................................. 13 
(2) Follow-up period ................................................................................................................................................................... 13 
(3) Telephone follow-up .............................................................................................................................................................. 13 
(4) Consistency of the examination time .................................................................................................................................... 13 
(5) Study termination .................................................................................................................................................................. 14 
3.2.3 Study duration .................................................................................................................................................... 14 
3.2.4 Sample size ................................................................................................................................................................. 14 
3.2.5 Study centers ............................................................................................................................................................. 14 
4. Evaluation criteria ......................................................................................................................................................... 14 
4.1 Clinical evaluation ...................................................................................................................................................... 14 
4.1.1 Demographic data............................................................................................................................................... 14 
4.1.2 Current medical history ...................................................................................................................................... 14 
4.1.3 Past history ......................................................................................................................................................... 14 
4.1.4 Medication situation ........................................................................................................................................... 14 
4.1.5 Family history and family diagram drawing ........................................................................................................ 15 
4.1.6 Physical examination........................................................................................................................................... 15 
4.2 Neuropsychological assessment (See Appendix 1-11 for details) .............................................................................. 15 
4.2.1 Mini-Mental State Examinations (MMSE) (80) ................................................................................................... 15 
4.2.2 Montreal Cognitive Assessment (MoCA) (81) ..................................................................................................... 15 
4.2.3 Neuropsychiatric Inventory Questionnaire (NPI-Q) (91) ..................................................................................... 15 
4.2.4 Geriatric Depression Scale (GDS) (92) ................................................................................................................. 15 
4.2.5 Modified Hachinski Ischemic Scale (m-HIS) (95) ................................................................................................. 15 
4.2.6 World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA 
AVLT) (84) ..................................................................................................................................................................... 15 
4.2.7 Trail Making Test (TMT) A and B (86) .................................................................................................................. 16 
4.2.8 Digit Span Test (Forward and Backward) (DST) (87)............................................................................................ 16 
4.2.9 Boston Naming Test (BNT) (88) ........................................................................................................................... 16 
4.2.10 Activities of daily living (ADL) (93) .................................................................................................................... 16 
4.2.11 Clinical Dementia Rating Scale (CDR) (83) ........................................................................................................ 16 
5. Imaging examination ..................................................................................................................................................... 16 
5.1 Imaging equipment and qualifications ...................................................................................................................... 16 
5.2 MRI ............................................................................................................................................................................. 16 
5.3 PET ............................................................................................................................................................................. 17 
5.3.1 FDG-PET .............................................................................................................................................................. 17 
5.3.2 11C-PIB PET .......................................................................................................................................................... 17 
5.4 Carotid ultrasound ..................................................................................................................................................... 17 
6. Laboratory examination ................................................................................................................................................ 17 

3 
 
6.1 Laboratory testing items ............................................................................................................................................ 17 
6.1.1 Genetic gene detection ....................................................................................................................................... 17 
6.1.2 Risk gene locus detection ................................................................................................................................... 17 
6.1.3 Body fluid biomarkers detection ......................................................................................................................... 17 
6.2 Collection and storage of biological specimens ......................................................................................................... 18 
6.2.1 Blood sample ...................................................................................................................................................... 18 
6.2.2 Cerebrospinal fluid sample ................................................................................................................................. 18 
7. Informed consent ........................................................................................................................................................... 18 
7.1 Inform benefits and risks ........................................................................................................................................... 18 
7.1.1 Benefits ............................................................................................................................................................... 18 
7.1.2 Risk ...................................................................................................................................................................... 18 
7.2 Inform rights and obligations ..................................................................................................................................... 18 
7.2.1 Rights .................................................................................................................................................................. 18 
7.2.2 Obligations .......................................................................................................................................................... 18 
7.3 Study termination: ..................................................................................................................................................... 19 
7.4 Confidentiality ............................................................................................................................................................ 19 
8. Safety and risk to the participant ................................................................................................................................. 19 
8.1 Neuropsychological testing ........................................................................................................................................ 19 
8.2 Lumbar puncture ....................................................................................................................................................... 19 
8.3 Blood collection ......................................................................................................................................................... 19 
8.4 Imaging ...................................................................................................................................................................... 19 
9. Ethics ........................................................................................................................................................................ 19 
9.1 Setting up internal related committees ..................................................................................................................... 19 
9.1.1 Academic committee .......................................................................................................................................... 19 
9.1.2 Data management committee ............................................................................................................................ 19 
9.1.3 Quality control committee .................................................................................................................................. 20 
9.1.4 Internal ethics committee ................................................................................................................................... 20 
9.2 Informed consent principle ........................................................................................................................................ 20 
10. Quality control .............................................................................................................................................................. 20 
10.1 Preparing researcher's case report form ................................................................................................................. 20 
10.2 Researcher training .................................................................................................................................................. 20 
10.3 Subject compliance .................................................................................................................................................. 21 
10.4 The researcher fills in the data requirements .......................................................................................................... 21 
11. Data management ......................................................................................................................................................... 21 
12. Statistical analysis ........................................................................................................................................................ 21 
13. Data sharing ................................................................................................................................................................. 21 
References ........................................................................................................................................................................... 23 
14. Appendix ....................................................................................................................................................................... 28 
 
 

4 
 
1. Study glossary 
Academic committee 
AC 
Alzheimer's disease 
AD 
Autosomal dominant Alzheimer disease 
ADAD 
Alzheimer's disease international 
ADI 
Activity of daily living 
ADL 
Amnestic mild cognitive impairment 
a-MCI 
Apolipoprotein 
APOE 
Boston naming test 
BNT 
Clinical dementia rating 
CDR 
Cognition and aging study 
COAST 
Case report form 
CRF 
Cerebrospinal fluid 
CSF 
Data management committee 
DMC 
Diagnostic and Statistical Manual-Fourth Edition, Text Revision 
DSM-IV-R 
Digit span test 
DST 
End diastolic velocity 
EDV 
Familial Alzheimer's disease 
FAD 
[18F]Fluorodeoxyglucose 
FDG 
Geriatric depression scale 
GDS 
Genome-wide association studies 
GWAS 
Intima-media thickness 
IMT 
Mild cognitive impairment 
MCI 
Modified Hachinski ischemic score 
m-HIS 
Mini-mental state examination 
MMSE 
Montreal cognitive assessment 
MoCA 
Magnetic resonance imaging 
MRI 
Medial temporal lobe atrophy 
MTA 
National Institute on Aging-Alzheimer’s Association 
NIA-AA 
National institute of neurological and communicative disorders 
and stroke-AD and related disorders association 
NINCDS-ADRDA 
Neuropsychiatric inventory 
NPI 
Positron emission tomography  
PET 
Principle investigator 
PI 
Pittsburgh compound B 
PIB 
Peak systolic velocity 
PSV 
Quality control committee 
QCC 
Sporadic Alzheimer's disease 
SAD 
Subcortical ischemic vascular disease 
SIVD 
Cerebral small vessel disease 
SVD 
Trail making test 
TMT 
Vascular dementia 
VaD 
Vascular cognitive impairment 
VCI 

5 
 
Vascular cognitive impairment with no dementia, 
VCIND 
World Health Organization-University of California Los 
Angeles, Auditory Verbal Learning Test 
WHO-UCLA AVLT 
White matter lesion 
WML 
 
 
2. Introduction  
2.1 Background and significance 
Dementia is a major cause of disability in the elderly. In the late stage, patients lose their ability to live independently and rely on 
other people's care. The main subtype of dementia is Alzheimer's disease (AD), followed by vascular dementia (VaD). Other subtypes 
include mixed dementia, frontotemporal dementia, Lewy body dementia, Parkinson's disease with dementia, alcoholic dementia, 
hydrocephalus dementia, post-traumatic dementia, etc. The number of dementia in China accounts for a quarter of the total number of 
dementia in the world, and the annual economic cost of AD alone has exceeded 1100 billion Chinese yuan, which brings heavy burden 
to the sustainable development of the country (1). 
A study reported that the prevalence of AD people over 65 years old in 1997 was 3.50%, and that of VaD was 1.10% (2). After that, 
studies have reported that the prevalence of dementia in people over 65 years old is 2.0-13.0% (3-7). In 2014 and 2019, two large-scale 
multicenter cross-sectional studies were carried out, respectively. The results showed that the prevalence of dementia (≥ 65 years old) 
was 5.14% and 5.60%, respectively, that of AD was 3.21%, and that of VaD was 1.50% (8, 9). For the first time, the team reported the 
regional differences in dementia prevalence in China (the highest in the West, the lowest in the South, the Central and the North are in 
the middle), urban-rural differences (rural areas are higher than urban areas, possibly due to low education), and the impact of age and 
gender. Only a few studies have reported the prevalence of other subtypes of dementia. The prevalence of mixed dementia is 1.5%, 
Parkinson's disease dementia 0.4%, and Lewy body dementia 0.2% (10, 11). The studies of incidence of dementia before 2010 were 
mostly single center. In 2016, a multicenter study reported that the incidence rate of dementia, AD and VaD in people aged 65 and above 
were 12.14, 8.15 and 3.13/1000 person year, respectively (12). The research on the prevalence and incidence rate of dementia were mostly 
based on single center and small sample. The research methods are not consistent, and there is lack of epidemiological data on other 
subtypes of dementia. Periodic large-scale, multicenter, consistent methods and standards are needed for updating data in a timely manner. 
The risk factors of dementia are mainly divided into genetics, comorbidity, lifestyle and other factors. Genetic factors include: 
carrying the ε 4 allele of apolipoprotein E (ApoE) gene (13), triggering receptor expressed on myeloid cells 2 (TREM2) gene(14), clusterin 
(CLU) gene (15), vascular endothelial growth factor (VEGF) gene (16), beta-secretase 1 (BACE1)(17), insulin degrading enzyme (IDE) 
gene (18), etc. Comorbidity factors include tension-type headache (19), migraine (20), sensory impairment (21), stroke (22), hypertension 
(23), hyperlipidemia (24), chronic nephropathy (25), insomnia (26), diabetes (24), hearing disorder (27), etc. Lifestyle factors include: 
smoking (24), secondhand smoke (28), sedentary behavior (29), bad drinking history (24), less physical exercise and cognitive activities 
(30), etc. Other risk factors include: living in the rural area (31), old age, low education level (22), sex (AD: female (24); VaD: male (32)), 
loneliness (33), weakness (34), zoster (35), high dose benzodiazepines (36), pesticides (37), exposure to trace elements (38), low folic 
acid and vitamin B12 and high homocysteine (39), high body mass index (BMI) (40) or unexpected reduction (41), etc. Protective factors 
are mainly divided into genetic factors, lifestyle and other factors. Genetic factors include: APOEε2 allele, Toll like receptor 9 (TLR9) 
gene (42), LDL receptor related protein 1 (LRP1) gene (43), etc. Lifestyle factors include: sports, outdoor activities, labor, social activities, 
intellectual activities, quitting smoking (44), healthy diet (45), supplement folic acid and vitamin B12 (46), etc. Other protective factors 
include: living in the urban area (31), high education level (44), high level of thiamine diphosphate (47), cantoness/mandarin bilingualism 
(48), Tai Chi (49), etc. At present, the research on dementia risk and protective factors is lack of quantitative and objective evaluation 
indicators, and through certain interventions to further clarify the impact of these factors in dementia. By further defining the risk and 
protective factors of dementia and regulating them on this basis, it is expected to prevent the onset or delay the progress of dementia. 
Genetics plays an important role in the pathogenesis of dementia. Take AD for example, AD can be divided into sporadic AD (SAD) 
and familial AD (FAD). The single gene association study of SAD has been conducted for more than 30 years, but the only recognized 
genetic susceptibility gene is APOE ε 4 allele (50). Other susceptibility genes, such as ACT, IDE, BACE1, MAPT, LRP1, were only 
confirmed in some populations (17, 51). At precent, many new AD susceptibility genes have been found in Europe and America through 

6 
 
genome wide association (GWAS), such as GAB2, CLU, PICALM, CD2AP, CD33, EPHA1, and ABCA7 (52-54). In 2018, also through 
GWAS, Japan found that SORL1 gene was related to the risk of AD (55). However, there is no report on the whole genome association 
of AD in China. The functional study of susceptible gene variation is of great significance to clarify the mechanism of related genes in 
the pathogenesis of AD. Most of these variation sites are located in gene regulatory regions, including promoter region and 3' untranslated 
region (3'UTR) (56, 57). FAD are mostly autosomal dominant. About 30% - 40% of FAD families are caused by PSEN1, PSEN2 and 
APP gene mutations. At present, more than 350 pathogenic mutations have been found in these three genes, including 289 PSEN1 
mutations, 48 PSEN2 mutations, and 58 APP mutations. New mutations are reported in AD mutation database every year 
(https://www.alzforum.org/mutations). At present, the genetic research of dementia and its main subtypes in the world is mostly based on 
Caucasian population, so further studies are needed to verify them in China's dementia population, and to explore the genetic etiology 
with Chinese characteristics. In addition, at present, the functional research on the pathogenic and susceptible genes of dementia is not 
comprehensive enough, and most of them focus on AD. There are few studies on the genetic mechanism of VaD and other subtypes of 
dementia. Therefore, it is of great significance to further explore the genetic variation, mutation and polymorphism of genes in dementia, 
and understand their distribution and mechanism of action in the pathogenesis.  
The studies of diagnostic markers of dementia mainly include biofluid, genetic and imaging markers. In the biofluid markers, some 
can reflect the typical pathophysiological changes of AD, such as amyloid β (Aβ) (58, 59), tau protein (T-tau, P-tau), others such as 
neurogranin (Ng) (60, 61), neurofilament light (NfL) (62, 63), visinin-like protein-1 (VLP-1) (64), chitinase-3-like protein-1 (YKL-40), 
tumor necrosis factors-α (TNF-α), soluble TNF receptors-1 (sTNFRs-1), TNF-α converting enzyme (TACE), interleukin 6 (IL-6) (65, 
66). Genetic markers include pathogenic genes and risk genes, and mutations of pathogenic genes such as APP, PSEN1 and PSEN2 (67-
73). Risk genes such as carrying APOEε4 (50). In imaging markers, MRI suggests that the atrophy of temporal olfactory area and 
hippocampus has important diagnostic value in AD (74). PET tracing technology can detect the levels of Aβ and tau in brain (75-77). 
These results are mainly based on Caucasian population, many of which have not been verified in Chinese population, and there is no 
clear cut-off value. The sensitivity and specificity of using single marker for early diagnosis of dementia is not enough, so it is necessary 
to explore the diagnostic efficacy of the combination of several markers in different stages of dementia in China. Meanwhile, developing 
early diagnosis system risk prediction model of MCI, AD (sporadic and familial) and VaD that are suitable for Chinese people, and 
promoting the application in clinical field, can reach the effective identification of high-risk or even asymptomatic population. Therefore, 
the population with disease tendency can receive early intervention, so as to prevent the occurrence of dementia. 
At present, the commonly used diagnostic criteria for AD are the National Institute of Neurological and Communicative Disorders 
and Stroke, and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) standard in 1984, the National Institute 
of Aging and Alzheimer's Association (NIA-AA) standard in 2011, and the International Working Group-2 (IWG-2) standard in 2014. 
The international diagnostic standards of VaD include: Diagnostic and Statistical Manual of Mental Disorders, fourth edition standard 
(DSM-Ⅳ), the International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10) standard, American 
Alzheimer's Disease Diagnosis and Treatment Center (ADDTC) standard, American National Institute of Neurological Disorders and 
Stroke National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement 
en Neurosciences (NINDS-AIREN) standard, American Stroke Association / American Heart Association (ASA / AHA) standard in 2011, 
American Psychiatric Association (APA) standard in 2013, and the International Society of Vascular Behavioural and Cognitive Disorders 
(Vas-Cog) standard in 2014 (78). The diagnostic standard of MCI was first proposed by Petersen in 1999. In 2003, the IWG revised the 
MCI diagnostic standard, which has become a widely used MCI diagnostic standard (79). The subtypes of frontotemporal dementia 
(FTD), dementia of Lewy body (DLB), Parkinson’s disease dementia (PDD) also have international diagnostic standards. However, due 
to the difference of sensitivity and specificity of the standards, as well as the influence of region and culture, their application in Chinese 
population is limited. In addition，whether there is memory clinic or dementia specialist greatly affects the diagnosis level of dementia 
in different hospitals (1)，and this calls for a promotion of health system in the whole country.. 
The evaluation of dementia patients usually includes cognitive function evaluation (including memory evaluation, attention / 
executive function evaluation, language function evaluation, visuospatial and structural ability, application, calculation), non-cognitive 
evaluation (mental behavior change), and daily function evaluation (personal living ability, social ability, work ability), etc. The main 
scale used in cognitive function assessment is Mini-mental State Examination (MMSE) (80), Montreal Cognitive Assessment test (MoCA) 

7 
 
(81), Alzheimer’s Disease Assessment Scale, cognitive component (ADAS-cog) (common scale of drug clinical trials), Vascular 
Dementia Assessment Scale, cognitive component (VaDAS-cog) (82), Clinical Dementia Rating scale (CDR) (83), World Health 
Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) (84), Rey auditory verb learning 
test (RAVLT) (85), trail making test (TMT) A and B (86), digital spaning test, forward and backward (DST) (87), verbal fluency test 
(VFT) (88), Boston naming test (BNT) (88), Rey-Osterriche complex figure test (ROCF) (89), clock drawing test (CDT) (90), etc. Non-
cognitive evaluation scales include neuropsychiatric inventory questionnaire (NPI-Q) (91), geriatric depression scale (GDS) (92), etc. 
Daily function evaluation scales include ability of daily living scale (ADL) (93), functional activities questionnaire (FAQ) (94), etc. In 
addition, there is the modified Hachinski ischemic index scale (m-HIS) used to distinguish AD from VaD (95). At present, most of the 
psychological assessment scales are translated from foreign versions or modified by domestic scholars according to the different 
characteristics of Chinese language and culture. However, the current modified version of the scales still cannot completely overcome 
the shortcomings in assessing the cognitive status of Chinese people, and there is no unified cut-off value, which is not beneficial to the 
diagnosis of the disease progression of dementia. Therefore, it is of great significance to develop psychological assessment scales with 
high sensitivity and specificity, in line with the Chinese people characteristics, through large-scale multi-center survey of the 
representative elderly population in the whole country, based on the changes brought about by China's society, culture and materials in 
recent years. 
As one of the early interventions of AD and dementia, non-pharmacologic treatment (NPT) has been studied more and more in 
recent years. At present, the NPT research on dementia mainly focuses on improving the lifestyle, physical exercise, music, cognitive 
training, risk factor control and so on. Lifestyle interventions are potential NPT methods for AD and other dementia, including diet and 
sleep habits, smoking, drinking and social interaction (96-99). Physical exercise as a common NPT method can improve the cognitive 
function of MCI patients and slow down the progression of AD (100-102). Physical exercise may improve cognitive function through 
oxidative stress, inflammation, metabolism and other mechanisms (103), and affect the brain structure related to dementia, such as 
hippocampus/parahippocampal area, anterior cingulate gyrus and prefrontal cortex (104). Music therapy can improve some cognitive 
functions of mild AD patients, especially episodic memory, executive function and general cognition, and also has a positive impact on 
mental and psychological health (105-107). Cognitive training can delay the onset of symptoms and improve the Aβ related memory 
deficit by preventing oxidative stress and changing the plasticity of white matter in the brain (108-110). At present, most of the NPT 
studies have a single sample, lack of quantitative and objective evaluation criteria, do not exclude other influencing factors (other 
comorbid diseases, gender, etc.). Furthermore, their neurobiological mechanism is not clear. It is necessary to explore the efficacy and 
potential neurobiological mechanism of NPT in AD and dementia through well-designed randomized controlled trials, and systematic 
and effective intervention programs (111). 
To popularize the basic concept of dementia, improve the public awareness and attention to dementia, and understand the symptoms 
in the pre-dementia stage, can make patients get timely diagnosis and effective intervention, which is conducive to the prevention of 
dementia. At present, the public awareness of dementia is not enough, especially for people over 60 years old, with low level of education 
and living in rural areas. Carry out relevant propaganda and education is needed (112). In addition, through psychological care, 
environmental care, rehabilitation training, cognitive training, physical training, scientific diet, reasonable living and other nursing 
knowledge education for dementia patients and caregivers, the quality of life of dementia patients can be improved to a certain extent, 
and the psychological stress and mental burden of caregivers can be reduced (113-115). 
Through the establishment and improvement of the Chinese cognitive and aging research cohort, this study can clarify and regularly 
update the data of the prevalence and incidence of dementia and its subtypes in China, and understand the risk and protective factors of 
dementia in China, explore its genetic characteristics and pathogenesis. Furthermore, by studying markers, assessment scales, diagnostic 
criteria and intervention methods, finally achieve early diagnosis and treatment of dementia, improve the diagnosis and treatment level, 
and provide basis for developing dementia prevention and control strategy. 
 
2.2 Specific aims 
The aim of this study is to establish and perfect the China Cognition and Aging Study (China COAST) cohort, to clarify the 
epidemiology, influencing factors, genetic characteristics, pathogenesis, disease characteristics and diagnosis and treatment status of 

8 
 
dementia and its subtypes in China. It is of great significance to establish a relatively comprehensive national database of cognitive 
disorders, improve the clinical diagnosis and treatment level of cognitive disorders, and formulate prevention and treatment strategies for 
dementia. The primary aims of China COAST are as follows: 
1. To use the prospective cohort to establish a large database research platform, so as to provide comprehensive epidemiological 
data, clinical and neuropsychological evaluation data, biological samples, and laboratory tests and imaging data. 
2. To update the prevalence and incidence rate of dementia and its subtypes every 2-3 years, and clarify the conversion pattern from 
normal elderly to MCI and from MCI to dementia. 
3. To explore the known or unknown protective and risk factors of dementia and its major subtypes (AD, VaD, other dementia). 
4. To discover new pathogenic genes and susceptible genes of dementia and its major subtypes (AD and VaD), as well as new 
mutation sites of known pathogenic genes. To study the genetic variation, mutation and polymorphism of PSEN1, PSEN2, APP and 
APOE genes in dementia patients, and to understand their distribution and roles in the pathogenesis. 
5. To study the biomarkers (body fluid, genetics, imaging) with diagnostic value of MCI, AD (sporadic and familial) and VaD, to 
define their cut-off values, and to establish prediction models. 
6. To study the diagnostic criteria of cognitive normal, MCI, dementia and their subtypes (clinical and molecular subtypes) in the 
cohort, and to make psychological assessment scales with high sensitivity and specificity, and in line with the characteristics of Chinese 
people. 
7. To find potentially modifiable risk factors for dementia and to study the prevention and intervention effect of non-pharmacological 
treatment on APOE ε4 carriers, MCI and AD or other dementia patients，which included improvements in education, nutrition, health 
care, and lifestyle changes. This needs a long time follow-up.8. To explore the relationship between dementia as well as its major subtype 
AD and cerebral and systemetic circulatory disorders (for example, mixed dmentia), as well as potential therapeutic strategies. 
9. To carry out investigation and researches about dementia related education, improve the awareness of dementia, and strengthen 
the management of dementia. 
 
3. Study design 
3.1 Research content 
1. Through the collection of basic demographic information and clinical data from the multi-center cohort, we will calculate the 
prevalence and incidence rate of AD, VaD, other dementia (mixed dementia, FTD, DLB, PDD, alcohol dementia, hydrocephalus dementia, 
post-traumatic dementia, etc.), and update the numbers every 1-2 years. 
2. To clarify the conversion pattern from normal elderly to MCI and from MCI to dementia. Through the collection and analysis of 
current medical history, past history, family history, living habits, drug use, physical examination and other information, we will explore 
the protective and risk factors of dementia and its main subtypes (AD, VaD, Other dementia), including age, gender, education level, 
rural/urban, marital status, parental dementia history, dietary habbit, blood pressure, drinking, smoking, diabetes, hyperlipidemia, 
cerebrovascular disease, heart disease, depression, hearing impairment, exercise habits (Tai chi, etc.), dementia specialist influence on 
patients, occupation, BMI, lifestyle changes, air pollution, head injury , social contact, low-income, and other unknown protective or 
risk factors. To investigate the role of ApoE gene, especially ApoEε4 in the disease onset and development, and to explore the non-
pharmacological interventions For the study purpose we do follow-up every 2or 3 years. 
3. By using exome sequencing, GWAS, WGS and other methods, we will search for new mutations of known pathogenic genes 
(APP, PSEN1, PSEN2) of AD in China, find new pathogenic genes and susceptible genes of dementia and its main subtypes (AD and 
VaD), and understand their distribution. We will explore the independent and combined effect of susceptibility gene variation on the risk 
of illness in Chinese AD population, and to obtain the key mutation sites that have a clear relationship with the incidence of AD. We will 
do regular follow up visits for the FAD members with new mutations of pathogenic genes, and clarify the important role of new mutations 
of pathogenic genes during the onset and progression of AD. 
4. We will collect the biofluids (blood, cerebrospinal fluid, urine, etc.) and 18F-FDG / 11C-PIB PET/MR multimodal imaging data 
from people with normal cognition, MCI, AD (sporadic and familial) and VaD, and conduct regular follow up. Discover and verify the 

9 
 
SAD related susceptible gene and FAD related pathogenic gene mutation. Through analyzing the imaging data (such as MRI brain 
regional volume, 18F-FDG PET and cortical Aβ load), cerebrospinal fluid and plasma markers (such as Aβ, T-tau and P-tau) and clinical 
features (such as psychiatric symptoms and age of onset), we will develop gene chip with high sensitivity and high specificity for early 
screening of dementia; develop diagnostic kits for biofluid markers (blood and cerebrospinal fluid); determine imaging cut-off values at 
all stages of dementia in Chinese people. We will do correlation analysis to establish early diagnosis and risk prediction model for 
dementia, and verify the newly developed instruments that can detect the peripheral markers of dementia patients and predict the disease 
progression in national large sample. 
5. Through the unified and standardized neuropsychological scales, including MMSE, MoCA, CDR, NPI, ADL, etc, we will conduct 
investigation to subjects in baseline and follow-up period, and analyze the changes of cognitive function, ability of daily life and mental 
behavior symptoms in different cognitive disorders. According to the social, cultural and material changes in China in recent years, we 
will develop psychological assessment scales with high sensitivity and specificity, and in line with the characteristics of Chinese people. 
Meanwhile, on the basis of the international diagnostic standards of various subtypes of dementia, combined with the etiology, clinical 
manifestations, scale classification, imaging characteristics, biofluid examination, etc., we will study the novel typing method and 
diagnostic standards of cognitive normal, MCI, dementia and its subtypes (clinical and molecular subtypes) in Chinese population. 
6. Through designing randomized controlled trials, we will study the systematic and effective NPT intervention program, including 
lifestyle (diet and sleep habits, smoking, drinking and social networking), health products, exercise habits, cognitive training, risk factor 
control, etc. We will explore the quantitative and objective evaluation criteria of NPT in AD and dementia, clarify its prevention and 
control efficacy on APOE ε4 carriers, MCI and dementia patients, and potential neurobiological mechanism. At the same time, we will 
carry out dementia related education in the community, improve the public knowledge, attention and awareness of dementia, so that 
patients can get early detection, early diagnosis and early intervention. 
7. To explore the relationship between dementia as well as its major subtype AD and cerebral circulatory disorders (cerebral ischemic 
and hemorrhage diseases, cerebral arteriosclerosis and stenosis, cerebral venous diseases, etc.), especially clarify the relationship between 
chronic cerebral ischemia and AD, as well as its effect on AD onset, and whether or not it’s risk factor for AD. Whether  the therapeutic 
strategies for cerebral circulatory disorders should be included in the treatment of AD. 
3.2 Research methods 
Through the establishment of a national multi-center cognition and aging cohort, this study will collect relevant demographic 
information and clinical data, biofluid samples, neuropsychological evaluation, imaging examination, blood examination and other 
comprehensive evaluation of study subjects, so as to study the epidemiology, influence factors, genetics and pathogenesis, diagnostic 
standards, prevention and control strategies of dementia and its subtypes. The study flow chart is as follows (figure 1): 

10 
 
 
 
 
3.2.1 Inclusion and exclusion criteria: 
Community population: age ≥ 55 years, male or female, with consent to participant the study. 
Hospital population: subjects are all over 18 years old. Through clinical evaluation, neuropsychological test, imaging examination, 
blood and cerebrospinal fluid examination, etc, we will comprehensively evaluate the cognitive function and various test measures. 
  
(1) MCI and its subtypes 
Inclusion criteria: 
1) Diagnosis according to 2004 Peterson's MCI criteria. 
2) CDR = 0.5. 
3) Memory loss is prominent, and may also be with other cognitive domain dysfunction. 
4) Insidious onset, slow progress. 
5) Not reaching the level of dementia. 

11 
 
Exclusion criteria: 
1) With history of stroke and a neurological focal sign, the imaging findings are consistent with cerebral small vessal disease (Fazekas 
score ≥ 2 points). 
2) Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic 
encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.). 
3) Other systemic diseases that can cause cognitive impairment (such as liver, renal and thyroid insufficiency, severe anemia, folic 
acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.). 
4) Mental and neurodevelopmental retardation. 
5) Contraindications to MRI. 
6) Suffering from a disease that cannot be combined with cognitive examination. 
7) Refuse to draw blood. 
8) Refuse to sign the informed consent at baseline 
 
(2) Sporadic Alzheimer’s disease (SAD) 
Inclusion criteria: 
1) Dementia is diagnosed according to the criteria described by the Diagnostic and Statistical Manual of Mental Disorders, Fourth 
Edition, Text Revision (DSM-IV-R). The diagnosis of AD is made using the National Institute of Neurologic and Communicative 
Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) or National Institute on Aging 
and the Alzheimer’s Association (NIA-AA) criteria. 
2) Subjects and their informed persons can complete relevant and follow- up examinations. 
3) Subjects or their authorized legal guardians sign the informed consent. 
Exclusion criteria: 
1) With a family history of dementia. 
2) Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic 
encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.). 
3) Other systemic diseases that can cause cognitive impairment (such as liver, renal and thyroid insufficiency, severe anemia, folic 
acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.). 
4) Mental and neurodevelopmental retardation. 
5) Contraindications to MRI. 
6) Suffering from a disease that cannot be combined with cognitive examination. 
7) Refuse to draw blood. 
8) Refuse to sign the informed consent at baseline 
 
(3) Familial Alzheimer’s disease (FAD) 
Inclusion criteria: 
1) Written informed consent obtained from participant or legal guardian prior to any study-related procedures. 
2) Members in FAD pedigree (FAD is defined as at least two first- degree relatives suffer from AD). 
3) Aged 18 (inclusive) or older. 
4) At least two persons who can provide reliable information for the study. 
Note: Dementia is diagnosed according to the criteria described by DSM-IV-R. The diagnosis of AD is made using NINCDS-
ADRDA or NIA-AA criteria. A diagnosis of MCI is assigned according to Petersen criteria. 
Exclusion criteria: 
1) Dementia caused by other factors such as depression, other psychiatric illnesses, thyroid dysfunction, encephalitis, multiple 
sclerosis, brain trauma, brain tumor, syphilis, acquired immunodeficiency syndrome (AIDS), Creutzfeldt-Jakob disease and other types 
of dementias such as vascular dementia (VaD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and Parkinson’s 

12 
 
disease dementia (PDD). 
2) MRI and laboratory tests do not support or rule out a diagnosis of AD. 
3) Severe circulatory, respiratory, urinary, digestive, hematopoietic diseases (such as unstable angina, uncontrollable asthma, active 
gastric bleeding) and cancer. 
4) Participant has severe psychiatric illness or severe dementia that would interfere in completing initial and follow-up clinical 
assessments. 
5) With history of alcohol or drug abuse. 
6) Pregnant or lactating women. 
7) No reliable insiders. 
8) Refuse to sign the informed consent at baseline. 
 
(4) Vascular dementia (VaD) 
Inclusion criteria: 
Diagnosis for probable VaD according to NINDS-AIREN diagnostic criteria. 
MRI inclusion criteria: 
All patients who meet clinical inclusion criteria should accept MRI scans which include an assessment of hippocampal volume. 
a. multiple (≥3) supratentorial subcortical small infarcts (3-20 mm in diameter) with or without any degree of white matter lesion 
(WML); or moderate to severe WML (Fazekas score ≥ 2), with or without small infarction; or ≥ 1 subcortical small infarct in key 
regions, such as caudate nucleus, globus pallidus, or thalamus. 
b. no cortical and watershed infarction, hemorrhage, hydrocephalus, or WML with specific causes (such as multiple sclerosis). 
c. no hippocampus or entorhinal cortex atrophy (MTA score = 0 point). 
Exclusion criteria: 
1) Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic 
encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.). 
2) Other systemic diseases that can cause cognitive impairment (such as liver insufficiency, renal insufficiency, thyroid insufficiency, 
severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.). 
3) With a history of mental illness or those with congenital mental retardation. 
4) Suffering from a disease that cannot be combined with a cognitive examination. 
5) Contraindications to MRI. 
6) Refuse to draw blood. 
7) Refuse to sign informed consent. 
 
(5) Normal control 
Inclusion criteria: 
1) Aged 18 (inclusive) or above. 
2) Normal MMSE and MoCA evaluations. MMSE>19 points for illiteracy, >24 points for those educated less than 7 years, >27 
points for those educated equal to or more than 7 years. MoCA>13 points for illiteracy, >19 points for those educated less than 7 years, >24 
points for those educated equal to or more than 7 years. 
Exclusion criteria: 
1) Subjects with abnormal MMSE or MoCA scores. 
2) Subjects with a history of cerebral infarction, traumatic brain injury or related manifestations in MRI. 
3) Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic 
encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.). 
4) Other systemic diseases that can cause cognitive impairment (such as liver, renal and thyroid insufficiency, severe anemia, folic 
acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.). 

13 
 
5) Mental and neurodevelopmental retardation. 
6) Suffering from a disease that cannot be combined with a cognitive examination. 
7) Contraindications to MRI. 
8) Refuse to draw blood. 
9) Refuse to sign the informed consent at baseline.  
 
3.2.2 Subject interview 
(1) Baseline and follow-up interview items 
During the follow-up of the subjects, the research supervisors were responsible for uploading data. Based on population, subjects 
were divided into community population and hospital population. Hospital population was further divided into MCI, FAD, SAD, VaD, 
normal control subjects. The supervisors of the centers monitored follow-up visits at different follow-up intervals in different population. 
The contents of the survey are shown in Table 1. 
Among them, the community population and normal control cohort only completed MMSE and MoCA for the baseline cognitive 
assessment part. If the MMSE and MoCA scores did not meet the normal population criteria at the time of follow-up visit, the subject 
should complete all the assessment scales. The investigator should judge whether the subject meets the criteria for inclusion in other 
groups in the cohort based on the assessment scores. 
Table 1. List of items during baseline and follow-up 
Items 
Baseline 
Follow-up 
Informed consent 
✔ 
Personal information 
✔ 
✔ 
Current medical history 
✔ 
✔ 
habits and customs 
✔ 
Family history 
✔ 
Past history 
✔ 
✔ 
Medication for cognitive impairment 
✔ 
✔ 
Physical examination 
✔ 
✔ 
Hachinski ischemic score 
✔ 
✔ 
Cognitive assessment 
✔ 
✔ 
Mental behavior assessment 
✔ 
✔ 
Daily and overall functional assessment 
✔ 
✔ 
Image examination 
✔ 
✔ 
Laboratory examination 
✔ 
✔ 
Clinical diagnoses 
✔ 
✔ 
 
(2) Follow-up period 
The follow-up period was 1-3 years, with an average of 1 year, depending on the subject. Among them, the follow-up period of FAD 
patients was performed according to the CFAN study protocol standard. 
(3) Telephone follow-up 
Subjects who were unable to face-to-face follow-up due to geographic reason or severe disease were evaluated by telephone follow-
up. The main purpose of telephone follow-up is to keep in touch with the subject, to grasp the subject's changes in cognitive function, 
learning ability, activities of daily living, social ability, and to collect information on adverse reactions (116). 
(4) Consistency of the examination time 

14 
 
All subjects were required to complete all examinations within a 4-week time window, including personal information, clinical 
assessment, neuropsychological scale testing, biomarker collection, and imaging examination. 
(5) Study termination 
The main reasons for termination of the study are as follows: 
1. Violation of the research protocol, no longer meet the inclusion criteria. 
2. The subject is unwilling or unable to participate. 
3. Withdraw informed consent. 
4. The study is terminated by the project leader or the coordination management center. 
5. Safety risks, subjects may withdraw according to their wishes at any time during the clinical trial if safety risks arise. 
6. Death. 
7. Other. 
3.2.3 Study duration 
This study is from February, 2008 to January, 2038, or longer. 
3.2.4 Sample size 
This study is planned to recruit 100 thousand subjects, from all participant centers that cover the North, South, East and Western 
parts of China.  
3.2.5 Study centers 
There are 68 participating research centers for this study, including 26 provinces, cities or autonomous regions. Detailed information 
can be found in Appendix 12. 
 
4. Evaluation criteria 
4.1 Clinical evaluation 
4.1.1 Demographic data 
The demographic data at baseline should be filled in as completely as possible, including: date of birth, age, family address, contact 
information, education level. At follow-up period(s), if information is changed, they will be updated. 
4.1.2 Current medical history 
The detailed and objective current medical history must be filled out by the physicians. If case report form (CRF) cannot describe 
the symptoms and characteristics of the subject in detail, fill in the blanks. 
Describe the specific manifestations of cognitive impairment, such as the specific manifestations of memory impairment 
(nearly/distant/ semantic forgetting); the specific manifestations of language barriers (difficulty in finding words, understanding, 
expressing, naming, writing, etc.); specific manifestations of disorientation (time, place, people, etc.); specific manifestations of 
personality and mental behavior (apathy, withdrawal, depression, agitation, wandering, abnormal sleep, antisocial behavior such as theft, 
etc.; the specific forms of hallucinations such as visual hallucinations, auditory hallucinations, etc.); manifestations of dyskinesia (such 
as ataxia, Parkinson-like dyskinesia, involuntary movements, etc.); implementation of dysfunction; spatial skills decline and other specific 
performance. 
Physicians should describe the extent of decline in each cognitive domain, whether cognitive impairment affects the patient's daily 
ability and social function, and how it behaves. 
4.1.3 Past history 
According to the current internationally recognized diagnostic criteria, the previous illness of the subject is diagnosed or confirmed, 
and the presence or absence of the relevant disease, the time of diagnosis and the course of the disease are recorded in detail. Try to let 
the subject or family provide the hospital's medical record/diagnostic certificate, etc., or the investigator will retrieve the patient's past 
medical records for inspection and confirmation.  
4.1.4 Medication situation 
The subject's medication needs to be documented in detail, including the name of the medication for the treatment of cognitive 
impairment and other diseases, the frequency of administration, and the adherence of the medication. Try to have the subject present a 

15 
 
medical record, drug package or prescription. 
4.1.5 Family history and family diagram drawing 
For subjects with a family history, the investigator should investigate in detail the incidence of each member of the family, and 
generally investigate the three generations of relatives of the patient. For cognitive impairment and suspected cognitive impairment in 
the family, the disease should be recorded in detail (e.g. age of onset, first symptom, progression of disease, involvement of each cognitive 
domain, age of dementia, diagnosis and treatment, clinical consistency with the proband, etc.). 
4.1.6 Physical examination 
Physical examinations include general medical examinations and neurological examinations performed by senior neurologists. 
4.2 Neuropsychological assessment (See Appendix 1-11 for details) 
Investigators should strictly follow the guidelines and scoring criteria, be consistent with different subjects and avoid inducing 
subjects. Patience is encouraged to complete the subject and, if needed, a short break. Check as far as possible in an independent, quiet 
space, try to be one-on-one with the subject to avoid outside interference. 
4.2.1 Mini-Mental State Examinations (MMSE) (80) 
The MMSE is a brief, frequently used screening instrument for dementia. The MMSE scale evaluates the following seven aspects: 
time orientation, location orientation, immediate memory, attention and computation, delayed memory, language, and visual space. There 
are a total of 30 topics. The total score ranges from 0 to 30. The test scores are closely related to the educational level. Higher scores 
indicate better cognitive function. 
4.2.2 Montreal Cognitive Assessment (MoCA) (81) 
The MoCA is, similar to the MMSE, a brief cognitive assessment designed to detect cognitive dysfunction at the MCI stage. This 
scale has been shown to have adequate sensitivity and specificity in clinical settings to detect suspected MCI. The MoCA evaluates a 
variety of cognitive domains including attention, executive function, memory, language, visual space, orientation, and computational 
capacity. The total score is 30 points. 
4.2.3 Neuropsychiatric Inventory Questionnaire (NPI-Q) (91) 
NPI-Q is a well-validated evaluation tool. It evaluates neuropsychiatric symptoms in AD based on interviews with informed 
individuals, with relatively short visit time (<15 minutes). It assesses the presence and severity of 12 neuropsychiatric features, including 
delusions, hallucinations, agitation/aggression, depression/bad mood, anxiety, euphoria, apathy, disinhibition, irritability/emotional 
instability, abnormal motor behavior, sleep/nighttime behavior, appetite and eating disorders. At the same time, the severity of the 
symptoms (1-3 points), frequency (1-4 points), and the degree of distress of the caregiver (0-5 points) are evaluated. 
4.2.4 Geriatric Depression Scale (GDS) (92) 
The GDS is a self-report scale designed to screen for symptoms of depression in the elderly and to measure the self feeling of the 
elderly within a week. The scale has a total of 30 items, including the following symptoms: low mood, reduced activity, irritability, 
withdrawal of painful thoughts, negative scores of the past, present and future. The total score is 0-10 points, which is normal; 11-20 
points, mild depression; 21-30 points, moderate to severe depression. 
4.2.5 Modified Hachinski Ischemic Scale (m-HIS) (95) 
The m-HIS can be used to identify VaD through clinical findings. It has a total of 8 items, and 12 points. The items include stepwise 
aggravation, complain of physical symptoms, emotional loss of control, hypertension history, which are scored 1 point each; acute onset, 
stroke history, neurological focal symptoms, nervous system focal signs, which are scored 2 points each. The total score is 0-12 points. 
The higher the evaluation score, the greater the possibility of VaD: those with a score of 4 or less are AD; those with a score of 7 or more 
are VaD. 
4.2.6 World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) 
(84) 
AVLT is a list learning task for evaluating multiple cognitive parameters related to learning and memory. In each of the three learning 
trials, 15 unrelated nouns are spoken out by the tester at the speed of one word per second, and the subjects immediately recall the words 
freely, which is called the immediate recall test. In addition, after 30-minutes delay of completing the unrelated test, the subject again 
freely recall the original 15-words list, which is to test delayed recall. Then the tester reads 30 words (including 15 learned words and 15 

16 
 
interference options), and asks the subject to judge whether it is a learned word, and records the number of correct words, which is a 
delayed recognition test. The results are expressed as the number of nouns that are correctly recalled in each trial. The scale examines the 
ability to enter, store, extract, pay attention, and vocabulary of memory, and the score increases with increasing educational level. 
4.2.7 Trail Making Test (TMT) A and B (86) 
Part A of TMT consists of 25 circles, numbered 1 to 25, and the tester instructs the subject to draw lines as fast as possible in 
increasing numerical order. Part B is also composed of 25 circles, but these circles are white circles (1-12) and black circles (1-13). 
Subjects need to alternately connect circles of different colors in numerical order. The completion performance of the subject is 
determined based on the number of correctly completed lines and the time required to complete. Although both the part A and part B rely 
on visual motion and perceptual scanning skills, part B requires considerable cognitive flexibility to complete the black and white 
transition connection under time pressure. 
4.2.8 Digit Span Test (Forward and Backward) (DST) (87) 
The DST requires the subject to repeat a sequence of numbers that are read aloud by the examiner. In the forward test, the subjects 
must repeat the numbers in the same order; in the backward test, the numbers are repeated in opposite order. The length of the digits 
gradually increases from 3 to 10 digits in the forward test, and gradually increases from 2 to 8 digits in the backward test, and each digit 
length includes two tests. The test is terminated when both tests are incorrect. The maximum score of the forward test is 10 points and 
that of the reverse test is 8 points. 
4.2.9 Boston Naming Test (BNT) (88) 
This visual naming based scale shows 30 items. The objects in the picture are presented to the subject in a pattern of easily identifiable 
first and then not easily identifiable. If the subject encounters difficulties in naming the object, the examiner will provide a clue prompt 
or an option prompt. Record respectively the correct number of independent initial naming, clue naming, and option naming. 
4.2.10 Activities of daily living (ADL) (93) 
The ADL scale can evaluate the daily activities of the subject comprehensively, accurately and quickly. It consists of the physical 
life self-care scale and the instrumental ADL. There are 14 items, including two parts: first, the physical life self-care scale has a total of 
6 items, including toilet, eating, dressing, grooming, walking and bathing; second, instrumental ADL has a total of 8 items, including call, 
shop, prepare meals, do housework, laundry, use transportation, take medicine and financing abilities. The higher the subject scores, the 
worse the ability of daily living. 
4.2.11 Clinical Dementia Rating Scale (CDR) (83) 
The CDR is a refinement of information that the doctor obtains through conversations with the patient and his/her family, and to 
assess the degree of impairment of the patient's cognitive function, and then to quickly assess the severity of the patient's condition. The 
assessment of cognitive domains consists of six items: memory, orientation, judgment and problem solving, work and social ability, 
family life and hobbies, and independent living ability. The judgment is in five levels, "normal CDR=0, suspected dementia CDR=0.5, 
mild dementia CDR=1, moderate dementia CDR=2, severe dementia CDR = 3". The CDR-SOB (CDR sum of box) total score is a simple 
sum of the scores of the six items. CDR sum of boxes adds up the 6 items, and the total score ranges from 0 to 18. As long as the score 
is greater than 0, the subject has at least one cognitive impairment. Generally, the change value of CDR sum of boxes can be used in 
clinical trials to obtain more accurate cognitive evaluation (117). CDR is a widely used measure of the severity of dementia. 
 
5. Imaging examination 
At each assessment, subjects will receive MRI, PET, and carotid ultrasound. PET imaging includes FDG-PET and amyloid PET 
scans. 
5.1 Imaging equipment and qualifications 
Xuanwu Hospital and each sub-center have advanced imaging equipment. Most centers have Siemens or GE full-body MRI scanner, 
and some centers have PET/MR integrated whole body scanner or PET scanner. Each center has the license for the use of radioactive 
drugs by the National Food and Drug Administration (fourth category) and has the qualification to prepare new drugs (tracers) for research 
and development. 
5.2 MRI  

17 
 
MRI should be performed within 1 month before or after neuropsychological testing (with no new vascular disease events). All 
subjects should be checked for MRI contraindications before MRI scanning, such as the presence of metal implants in vivo. Remove 
active metal objects from the body before examination. After the subjects lie down, his right temple is used as a stereotactic marker, and 
the scan follows given directions. Three dimensional T1 weighted images of the whole brain were obtained. All subjects will undergo 
regular scan (T1WI, T2WI, FLAIR, DWI, MRA) and hippocampal phase scan (coronal T1-FLAIR sequence). Image acquisition is 
completed by radiology department of each center, stored and transmitted in DICOM format, and then image processing is carried out to 
obtain brain volume, cortex thickness and other indicators. Fazekas score and MTA score were obtained and used as location and 
quantitative indicators of white matter lesions and gray matter atrophy.  
5.3 PET 
5.3.1 FDG-PET 
FDG-PET can detect abnormal brain metabolism in patients with dementia, and should be performed within 1 month before or after 
neuropsychological examination (with no new vascular disease event). Fasting for at least 6 hours before examination, and fasting blood 
glucose was measured. Blood glucose levels should be <140 mg / dL (7.8 mmol/L). Image acquisition is completed by radiology 
department of each center, stored and transmitted in DICOM format, and then image processing is carried out to obtain whole brain and 
regional standard uptake value ratio (SUVR), and used as location and quantitative indicators of brain metabolic function. 
5.3.2 11C-PIB PET 
Amyloid tracer [N-methyl-11C]2-[4'-(methylamino) phenyl]-6-hydroxybenzothiazole (11C-PIB) is the mostly studied and relatively 
mature Phenothiazine Aβ imaging agent, which is a 11C-labeled derivatives of Thioflavin-T. It can specifically bind to Aβ plaques in the 
brain of AD patients and is used for positioning and quantitative analysis of Aβ in brain. 11C-PIB PET can differentiate AD and normal 
patients in the early and middle stages of the disease, reflect the pathological changes of brain tissue, provide more objective data for 
early diagnosis. Further combined with clinical history, laboratory tests, neuropsychology scale and structural imaging results, it can help 
improve the accuracy of the diagnosis to guide early treatment. Image acquisition is completed by radiology department of each center, 
stored and transmitted in DICOM format, and then image processing is carried out to obtain whole brain and regional standard uptake 
value ratio (SUVR), and used as location and quantitative indicators of Aβ deposition. 
5.4 Carotid ultrasound 
Carotid ultrasound can clearly demonstrate the vascular intima-media thickness, the location and size of plaque, the degree of 
vascular stenosis, and analyze hemodynamics. It plays a key role in the assessment and diagnosis of vascular-related diseases caused by 
atherosclerosis. Carotid ultrasound examination should be performed within 1 month before or after neuropsychological examination 
(with no new vascular disease event). An experienced ultrasound physician is required to perform the operation according to "Guidelines 
for Carotid Ultrasound Examination". Longitudinal and transverse section scanning are performed from frontal and lateral directions. 
Observe and record the peak systolic velocity (PSV), end diastolic velocity (EDV), intima-media thickness (IMT) and plaque (diameter, 
number, acoustic properties) of internal carotid artery, common carotid artery and carotid bifurcation. 
 
6. Laboratory examination  
6.1 Laboratory testing items 
6.1.1 Genetic gene detection 
PS1, PS2, APP, APOE and other genetic gene tests are performed on cognitive normal and dementia individuals in ADAD cohort 
and unknown mutation cohort. Collect the genetic information and biological materials of familiar dementia pedigree to help the basic 
and clinical research for the pathogenesis of dementia. 
6.1.2 Risk gene locus detection 
Conduct whole-exon analysis, genome-wide analysis, whole genome association analysis for each enrolled participant, using case-
control methods to detect, study and analyze novel risk gene loci that are disease relevant. Explore new pathogenic genes, mechanisms, 
and risk pathways to provide genetic basis for disease prevention and control. 
6.1.3 Body fluid biomarkers detection 
Conduct biomarkers detection in cerebrospinal fluid, blood, urine and saliva for each enrolled group, including blood and urine 

18 
 
routine tests, biochemistry, electrolytes and coagulation function tests, cerebrospinal fluid routine and biochemistry tests, etc. Special 
items include Aβ40, Aβ42, t-tau, p-tau and neurogranin in cerebrospinal fluid and blood to study and explore early diagnostic biomarkers 
and risk predictors of disease progression. 
6.2 Collection and storage of biological specimens 
6.2.1 Blood sample 
Each participant requires fasting blood collection in the morning and 8ml of peripheral blood is drawn. 5ml is injected into purple 
head anticoagulation tube, and 3ml is injected into red head non-anticoagulated tube. Name and number are signed on each blood 
collection tube. Centrifuge within 2 hours. After the purple head anticoagulation tube is centrifuged at 2000 rpm for 10 minutes, aspirate 
upper layer plasma by pipette and retain the remaining blood sample in the tube. After the red head non-anticoagulation tube is centrifuged 
at 2000 rpm for 10 minutes, the serum is pipetted and distributed into two of 1.5ml centrifugal tubes, about 500μl per tube. Name, number 
and the type of specimen are signed on each centrifugal tube (serum is labeled Q, while plasma is J). Centrifugal tubes are immediately 
stored at -80°C, while the anticoagulation tubes are stored at -20°C fridge. 
6.2.2 Cerebrospinal fluid sample 
Lumbar puncture should be done in the morning. To eliminate the impact of puncture bleeding on the quality of cerebrospinal fluid 
specimens, the first 1-2 ml of CSF should be discarded. 10ml CSF for biomarker analysis should be collected. Centrifuge within 2 hours 
after collection (2000 rpm for 10 minutes), then pipette and distribute the supernatant into ten of 1.5ml centrifugal tubes, 1 ml per tube. 
Centrifugal tubes are immediately stored at a -80°C fridge. 
 
7. Informed consent 
In this study, a series of memory and intelligence tests will be performed on participants, and if necessary, auxiliary examination 
will be arranged to confirm the diagnosis. After that, regular follow-up will be arranged for each person to tract the change of disease 
status. Participants and their families should be informed that they should sign an informed consent form after fully understanding the 
research, and should be reminded that participation in the study is voluntary. 
According to the current edition of the Declaration of Helsinki, the principle of informed consent will be implemented before 
protocol procedures are carried out. Information about the research content should be provided in both oral and written form and reviewed 
by an ethics committee. Subjects, relatives and guardians must have ample opportunity to inquire about details of the study. The informed 
consent should be in the language and script that subjects or legal representative can fully understand. During the clinical study, subjects 
can keep abreast of their research information. 
Informed consent will be recorded by using a written document approved by the Ethics Committee and signed by the subject and/or 
legally authorized representative. The written informed consent document will embody the elements of informed consent as stated in the 
Helsinki Declaration and will comply with local regulations. Informed consent should mainly include the following contents: 
7.1 Inform benefits and risks  
7.1.1 Benefits 
This study can help clinicians understand patient's disease and enable participants to obtain good and free medical services, such as 
free neuropsychological assessment, neurology physical examination, as well as follow-up observation and consultation.  
7.1.2 Risk 
The entire research process may occupy a certain period of time of the participants, but will not cause any physical harm. 
7.2 Inform rights and obligations  
7.2.1 Rights 
Research clinicians introduce research process to participants and their families, and emphasize that participation in the study is 
voluntary. All participant-related events during the study are informed in time so that participants can decide whether to continue or not. 
Participants and their families can refuse to participate or withdraw at any time during the study without affecting the participants’ own 
medical care or causing other benefit loss. 
7.2.2 Obligations 
Insist the principle of voluntary and sign the informed consent form before the study begins. Obey the arrangement of research and 

19 
 
cooperate with the research clinicians. Do not use other drugs without authorization during the study period. If must, please consult the 
research clinicians before usage and inform after usage. 
7.3 Study termination: 
If continuing to participate in the study is no longer in the best interests of the participants, the research clinicians will recommend 
participants to withdraw from the study. If there is a potential risk to the health of participants, the research institution or research clinician 
can terminate the study after informing the participants and their families. 
7.4 Confidentiality  
The records of participants will be kept properly in strict confidence, and only those who obtain authorization can preview the 
records. The ethics committee and the National Food and Drug Administration inspectors are allowed to review records, but the name, 
contact information and identification certificates of participants will not appear in the review report. 
 
8. Safety and risk to the participant 
8.1 Neuropsychological testing  
Participants and caregivers may feel tired, boring or embarrassing about neuropsychological testing. If they still cannot cooperate 
after being persuaded by the research clinician, they can choose to rest for a while before starting again. any problems of the participants 
detected by the research clinicians through neuropsychological tests (such as cognitive decline, depression, etc.) might expose the 
participants to unemployment, loss of medical insurance or other discrimination. Therefore, research clinicians should pay attention to 
the method of notification and avoid these events. 
8.2 Lumbar puncture 
The participants may have local discomfort at the lumbar puncture site, as well as back pain, neck stiffness and shoulder pain. The 
puncture site may appear bruising, swelling or rash, and the dizziness or headache may occur for the participants after lumbar puncture. 
The risk of other related complications is very rare, including the infections of puncture site, allergies to local anesthetics or disinfectants, 
and the injury of spinal nerve. 
8.3 Blood collection 
Slight discomfort, bruising, bleeding or infection at the venipuncture site. Very few participants may faint during or after the puncture. 
8.4 Imaging 
Participants may be allergic to the contrast agent or have radioactive substance radiation exposure risk during the MRI or PET 
inspection. Participants with metal implants may experience implant displacement during exposure to magnetic fields. Claustrophobia 
and anxiety may occur on the participants for lying in enclosed spaces. 
 
9. Ethics 
9.1 Setting up internal related committees 
Both main unit and sub units are required to pass ethical review. China COAST consists of several committees that work together 
to conduct research. Details are as follows:  
9.1.1 Academic committee 
China COAST study is mainly managed by an academic committee consisting of the principle investigator (PI) of main unit, all core 
members, and the PI of each participating unit. The Academic committee will work with the data management committee and the quality 
control committee to ensure that the China COAST program is conducted in accordance with the prescribed research design and 
methodology and will be responsible for the review of research protocol that is related to article writing. 
9.1.2 Data management committee 
China COAST data can be used by qualified academic or research staff to maximize the value of research data. The data management 
committee is responsible for managing the storage of data, periodically generating data sets, and accepting supervion by the quality 
control committee to ensure the completion and accuracy of data. To acquire the China COAST research data, an application must be 
submitted to the academic committee. After the research application is approved, the data management committee is responsible for 
extracting and distributing data and data statistics. 

20 
 
9.1.3 Quality control committee 
Quality control must be performed in real-time during the data collection phase to ensure that enrolled subjects meet the inclusion 
and exclusion criteria of the study, identify missing or abnormal items, assess the consistency of longitudinal follow-up, and clarify the 
status of the subject (continue follow-up or termination). The quality control committee is responsible for reviewing the standardization 
of collection, transportation, storage and analysis of biological samples; whether the imaging data and clinical information provided by 
each sub-center meet the requirements of the research program, and if there is any inconsistency, the quality control committee will 
request the research unit to provide missing or clarify contradictory information. The quality control committee is also responsible for 
the training of researchers to facilitate the consistency and labeling of the entire study. 
9.1.4 Internal ethics committee 
Internal ethics committee reviews and approves the written informed consent statements of each participating unit, and provide 
written statements to the subjects and/or their authorized representatives. The research ethics committee is responsible for reviewing the 
overall research protocol. If any accident or issue that affects the safety of the subject occurs during the research process, the research 
unit must immediately report to the research ethics committee. The committee organizes an internal meeting to deal with various issues 
in a timely manner and keeps records in written form. 
9.2 Informed consent  
The principle of informed consent will be implemented before protocol procedures are carried out. Information about the research 
content should be provided in both oral and written form and reviewed by a research ethics committee.  
Participants, their relatives, guardians or authorized representatives and study partners must be given ample opportunity to inquire 
about details of the study. The consent form generated by the investigator must be approved, along with the protocol. Consent forms must 
be in a language fully comprehensible to the prospective participants and/or their authorized representatives. Informed consent will be 
documented by the use of a written consent form approved by the REB and signed by the participant and/or an authorized representative. 
The written consent document will embody the elements of informed consent as stated in the Helsinki Declaration and will comply with 
local regulations. In any case, participants and their legal representatives should sign an informed consent form after fully understanding 
the research information. Informed consent signed by each participant must be kept on file by the investigator for possible review by 
regulatory authorities and/or monitors. The informed consent will cover consent for the study including the genetic research as well. 
Consent forms will specify that DNA and other biomarker samples including imaging are for research purposes only; the research tests 
are not diagnostic in nature and participants will not be informed of their test results. The informed consent will specify that Xuan Wu 
Hospital, Capital Medical Unversity will receive and store research data, MRI data and samples. 
 
10. Quality control 
The sponsors and research units of the research should adopt the standard operating procedures established by the quality control 
committee to ensure the implementation of quality control and quality assurance system of clinical research. The quality control 
committee verifies all observations and findings in clinical trials to ensure data reliability and to ensure that conclusions from clinical 
trials are derived from raw data. Quality control must be used at every stage of data processing to ensure that all data is reliable and 
processed correctly. 
10.1 Preparing researcher's case report form 
The CRF is prepared by the lead investigator. The main contents include informed consent, personal information of subjects, current 
medical history, living habits, family history, past history, medication for cognitive impairment, physical examination, Hachinski ischemic 
score, cognitive assessment, psychobehavioral assessment, daily and overall functional assessment, imaging examination, laboratory test, 
and clinical diagnosis. 
10.2 Researcher training 
Before the start of clinical research, the quality control committee convenes the researchers of each test center to conduct centralized 
and unified training, so that researchers can understand and be familiar with the research protocol, the researcher's manual, the CRF, and 
understand the various scales. 
The evaluators of clinical evaluation include physicians, nurses, and caregivers. The preparation, implementation, score evaluation, 

21 
 
and interpretation of the test results are standard and uniform, and through the centralized training, the evaluators achieve the consistency 
standard in the classification of the scales, and are required to be consistent for the test environment and test sequence of the subjects, so 
as to reduce the impact of human or environmental factors. After the training is completed, an exam is organized to test whether the 
evaluators have reliable testing skills. 
10.3 Subject compliance 
Sign the informed consent form. 
The investigator should carefully implement informed consent so that the subject fully understands the test requirements and 
cooperates with the test. The sponsor provides free trial medication, laboratory examination fees, etc. 
10.4 The researcher fills in the data requirements 
The investigator should ensure that the data is true, accurate, complete, and timely loaded into the CRF and uploaded. 
For all subjects who have filled in the informed consent form and are screened to be qualified for entering the test, the investigator 
must record the observed information in the CRF carefully and in detail, without empty entries or missing items. 
All data in the CRF needs to be checked against the subject's original medical record data. 
CRF can only be crossed when making any corrections, and modified by the side, with the signature and date of the researcher. 
The original test sheet (or copy) and imaging report form (or copy) are pasted on the test sheet paste place in the study medical 
record. 
Data that are significantly higher or lower or outside the clinical acceptance range should be verified or reexamined and made 
necessary instructions by the investigators. 
 
11. Data management 
All demographic, clinical, neuropsychological and imaging laboratory data are first registered in the CRF form by the researchers 
in each participating unit. Relevant personnel enter the data into the China COAST data network management platform after initial review 
and verification, and manage and share the multi-center entry data through a multi-center network management platform. The data 
management committee completes the monitoring, review and entry of data from each research center, including computer automatic 
verification and manual quality control by website data monitoring personnel. 
The data management committee discusses and decides that the main research unit has access to the data of all research units, and 
each participating unit only has access to the data of its own unit. After the portal site entry, there is a simple custom search engine that 
can be used to query data types and specific data. The data will be provided to China COAST inspectors in a phased manner, and virtually 
“isolated” until the quality control process is completed, and only the data management committee members and those responsible for 
completing the quality control procedures can access them. After the quality control is completed, the data will be released from the 
quarantine area and accessible to authorized users. The MRI and PET imaging data are stored as an image data file (file extension .dcm) 
conforming to the DICOM 3.0 standard, and the imaging materials are sent to the imaging center platform. 
 
12. Statistical analysis 
To ensure data quality, the data management committee will periodically review the data to determine if they meet the original 
statistical expectations. The statistical department of the data management committee will implement China COAST data statistics quality 
control, mainly for abnormal and missing data monitoring, and compare between research centers. The data management committee will 
generate relevant data sets and distribute them to researchers. The statistical department will then participate in statistical analysis and 
article writing, and use professional statistical software such as SAS and SPSS in consultation with the author. The statistics department 
will be responsible for writing the analysis statistics section of the article. If the researchers choose to do their own analysis, the statistical 
department will make statistical comments on the manuscript that they submit. 
 
13. Data sharing 
The principle of data sharing is cooperation, and data sharing is coordinated by academic committee and data management committee. 
The data management committee generates data sets every six months through data freezing for quality control and research personnel 

22 
 
to use. For data access rights, sub-center researchers can independently use the data they collect themselves, and based on the amount 
and completeness of the household data they provide, they can be co-authored in articles published by China COAST or apply for more 
complete data for independent analysis and article writing. Researchers writing articles using China COAST data should indicate in the 
article that the data is from the China COAST or China COAST study group. 
Investigators are required to submit an application to the academic committee by e-mail, including the research protocol and the 
type, quantity and format of the application data. The academic committee assesses the scientificity and feasibility of the research protocol. 
If the research proposal lacks scientificity or the information submitted is incomplete, the application will not be approved. The academic 
committee will also give amendment suggestions for the research proposal. After repeated communications and consultations with the 
applicant to determine the final version of the research protocol, the statistical department will organize the data and send it to the sub-
centers or independent non-China COAST researchers. All researchers are committed to protect the privacy of the subject and need to 
ensure that the data will not be reassigned to other researchers or institutions. 
 
 
 

23 
 
References 
1. 
Jia L, Quan M, Fu Y, Zhao T, Li Y, Wei C, et al. Dementia in China: epidemiology, clinical management, and research advances. 
Lancet Neurol. 2020;19(1):81-92. 
2. 
Zhang ZX, Zahner GEP, Roman GC, Liu J, Hong Z, Qu QM, et al. Dementia subtypes in China - Prevalence in Beijing, Xian, 
Shanghai, and Chengdu. Arch Neurol-Chicago. 2005;62(3):447-53. 
3. 
Chen RL, Ma Y, Wilson K, Hu Z, Sallah D, Wang JJ, et al. A multicentre community-based study of dementia cases and 
subcases in older people in China-the GMS-AGECAT prevalence and socio-economic correlates. Int J Geriatr Psych. 
2012;27(7):692-702. 
4. 
Rodriguez JJL, Ferri CP, Acosta D, Guerra M, Huang YG, Jacob KS, et al. Prevalence of dementia in Latin America, India, and 
China: a population-based cross-sectional survey. Lancet. 2008;372(9637):464-74. 
5. 
Yan F, Li SR, Huang YQ, Li G, Liu J, Gong JK, et al. Longitudinal Study on Dementia in an Urban Community of Beijing City 
in Two Decades. Chinese Mental Health Journal. 2008;22(2). 
6. 
Sun Y, Lee HJ, Yang SC, Chen TF, Lin KN, Lin CC, et al. A Nationwide Survey of Mild Cognitive Impairment and Dementia, 
Including Very Mild Dementia, in Taiwan. Plos One. 2014;9(6). 
7. 
Yang L, Jin XQ, Yan J, Jin Y, Yu W, Wu HB, et al. Prevalence of dementia, cognitive status and associated risk factors among 
elderly of Zhejiang province, China in 2014. Age Ageing. 2016;45(5):707-11. 
8. 
Jia J, Wang F, Wei C, Zhou A, Jia X, Li F, et al. The prevalence of dementia in urban and rural areas of China. Alzheimers 
Dement. 2014;10(1):1-9. 
9. 
Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, et al. Prevalence of mental disorders in China: a cross-sectional 
epidemiological study. Lancet Psychiatry. 2019;6(3):211-24. 
10. Yu BC，Xu RH，Wei WZ，Zhong WH，He JZ，Qi LJ, et al. Study of the prevalence of dementia and major subtypes in senile 
male veterans. People’s Military Surgeon. 2011;S1. 
11. Zhang GC，Zhao BL，Xu SZ，Shi YB. A survey of prevalence of senile dementia and Parkinson disease. Journal of Clinical 
Psychological Medicine. 2001;3. 
12. Yuan J, Zhang Z, Wen H, Hong X, Hong Z, Qu Q, et al. Incidence of dementia and subtypes: A cohort study in four regions 
in China. Alzheimers Dement. 2016;12(3):262-71. 
13. Zheng L, Duan J, Duan X, Zhou W, Chen C, Li Y, et al. Association of Apolipoprotein E (ApoE) Polymorphism with Alzheimer's 
Disease in Chinese Population. Curr Alzheimer Res. 2016;13(8):912-7. 
14. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of 
Alzheimer's disease. N Engl J Med. 2013;368(2):107-16. 
15. Yu JT, Ma XY, Wang YL, Sun L, Tan L, Hu N, et al. Genetic variation in clusterin gene and Alzheimer's disease risk in Han 
Chinese. Neurobiol Aging. 2013;34(7):1921 e17-23. 
16. Yuan Q, Zuo X, Jia J. Association between promoter polymorphisms of vascular endothelial growth factor gene and sporadic 
Alzheimer's disease among Northern Chinese Han. Neurosci Lett. 2009;457(3):133-6. 
17. Wang S, Jia J. Promoter polymorphisms which modulate BACE1 expression are associated with sporadic Alzheimer's disease. 
Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):159-66. 
18. Wang F, Shu C, Jia L, Zuo X, Zhang Y, Zhou A, et al. Exploration of 16 candidate genes identifies the association of IDE with 
Alzheimer's disease in Han Chinese. Neurobiol Aging. 2012;33(5):1014 e1-9. 
19. Yang FC, Lin TY, Chen HJ, Lee JT, Lin CC, Kao CH. Increased Risk of Dementia in Patients with Tension-Type Headache: A 
Nationwide Retrospective Population-Based Cohort Study. PLoS One. 2016;11(6):e0156097. 
20. Chuang CS, Lin CL, Lin MC, Sung FC, Kao CH. Migraine and risk of dementia: a nationwide retrospective cohort study. 
Neuroepidemiology. 2013;41(3-4):139-45. 
21. Luo Y, He P, Guo C, Chen G, Li N, Zheng X. Association Between Sensory Impairment and Dementia in Older Adults: 
Evidence from China. J Am Geriatr Soc. 2018;66(3):480-6. 
22. Xu S, Jin X, Liu C, Jin Y, Xu Y, Chen L, et al. Investigating the Prevalence of Dementia and Its Associated Risk Factors in a 
Chinese Nursing Home. J Clin Neurol. 2017;13(1):10-4. 
23. Liang X, Shan Y, Ding D, Zhao Q, Guo Q, Zheng L, et al. Hypertension and High Blood Pressure Are Associated With 
Dementia Among Chinese Dwelling Elderly: The Shanghai Aging Study. Front Neurol. 2018;9:664. 
24. Xue H, Sun Q, Liu L, Zhou L, Liang R, He R, et al. Risk factors of transition from mild cognitive impairment to Alzheimer's 
disease and death: A cohort study. Compr Psychiatry. 2017;78:91-7. 
25. Bai K, Pan Y, Lu F, Zhao Y, Wang J, Zhang L. Kidney function and cognitive decline in an oldest-old Chinese population. 
Clin Interv Aging. 2017;12:1049-54. 
26. Shi L, Chen SJ, Ma MY, Bao YP, Han Y, Wang YM, et al. Sleep disturbances increase the risk of dementia: A systematic review 
and meta-analysis. Sleep Med Rev. 2018;40:4-16. 
27. Lao ML ZH, Yi XN, et al. the epidemiological investigation of Alzheimer's disease in Hainan Island. Chinese Journal of 
Gerontology. 2011;31(20):4016-8. 
28. Anstey KJ, Chen R. Invited Commentary: Secondhand Smoke-an Underrecognized Risk Factor for Cognitive Decline. Am J 

24 
 
Epidemiol. 2018;187(5):919-21. 
29. Ku PW, Liu YT, Lo MK, Chen LJ, Stubbs B. Higher levels of objectively measured sedentary behavior is associated with worse 
cognitive ability: Two-year follow-up study in community-dwelling older adults. Exp Gerontol. 2017;99:110-4. 
30. Gao M, Kuang W, Qiu P, Wang H, Lv X, Yang M. The time trends of cognitive impairment incidence among older Chinese 
people in the community: based on the CLHLS cohorts from 1998 to 2014. Age Ageing. 2017;46(5):787-93. 
31. JH G. Incidence of Alzheimer in Persons over 60 Years Old in Taizhou City and Influencing Factors. Medicine and Society. 
2018;31(6). 
32. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al. Incidence and etiology of dementia in a large elderly 
Italian population. Neurology. 2005;64(9):1525-30. 
33. Zhong BL, Chen SL, Conwell Y. Effects of Transient Versus Chronic Loneliness on Cognitive Function in Older Adults: Findings 
From the Chinese Longitudinal Healthy Longevity Survey. Am J Geriatr Psychiatry. 2016;24(5):389-98. 
34. Ma L, Zhang L, Zhang Y, Li Y, Tang Z, Chan P. Cognitive Frailty in China: Results from China Comprehensive Geriatric 
Assessment Study. Front Med (Lausanne). 2017;4:174. 
35. Chen VC, Wu SI, Huang KY, Yang YH, Kuo TY, Liang HY, et al. Herpes Zoster and Dementia: A Nationwide Population-Based 
Cohort Study. J Clin Psychiatry. 2018;79(1). 
36. Chan TT, Leung WC, Li V, Wong KW, Chu WM, Leung KC, et al. Association between high cumulative dose of 
benzodiazepine in Chinese patients and risk of dementia: a preliminary retrospective case-control study. Psychogeriatrics. 
2017;17(5):310-6. 
37. Yan D, Zhang Y, Liu L, Yan H. Pesticide exposure and risk of Alzheimer's disease: a systematic review and meta-analysis. Sci 
Rep. 2016;6:32222. 
38. KB L. Study on the relationship between Serum Trace element level and Alzheimer's Disease and Depressio. Shandong: 
Shandong University; 2008. 
39. Ma F, Wu T, Zhao J, Ji L, Song A, Zhang M, et al. Plasma Homocysteine and Serum Folate and Vitamin B12 Levels in Mild 
Cognitive Impairment and Alzheimer's Disease: A Case-Control Study. Nutrients. 2017;9(7). 
40. Xi J, Ding D, Zhao Q, Liang X, Zheng L, Guo Q, et al. Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression 
from Mild Cognitive Impairment to Alzheimer's Disease: the Shanghai Aging Study. Curr Alzheimer Res. 2020. 
41. Rabin JS, Shirzadi Z, Swardfager W, MacIntosh BJ, Schultz A, Yang HS, et al. Amyloid-beta burden predicts prospective 
decline in body mass index in clinically normal adults. Neurobiol Aging. 2020. 
42. Wang YL, Tan MS, Yu JT, Zhang W, Hu N, Wang HF, et al. Toll-like receptor 9 promoter polymorphism is associated with 
decreased risk of Alzheimer's disease in Han Chinese. J Neuroinflammation. 2013;10:101. 
43. Yuan Q, Wang F, Xue S, Jia J. Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the 
northern Chinese Han population. J Clin Neurosci. 2013;20(2):253-6. 
44. Deng J, Cao C, Jiang Y, Peng B, Wang T, Yan K, et al. Prevalence and effect factors of dementia among the community 
elderly in Chongqing, China. Psychogeriatrics. 2018;18(5):412-20. 
45. Polito CA, Cai ZY, Shi YL, Li XM, Yang R, Shi M, et al. Association of Tea Consumption with Risk of Alzheimer's Disease and 
Anti-Beta-Amyloid Effects of Tea. Nutrients. 2018;10(5). 
46. L J. A case-control study on the relationship between folic acid, vitamin B12, methionine cycle products and Alzheimer's 
disease. Tianjin2015. 
47. Wang C, Fei G, Pan X, Sang S, Wang L, Zhong C, et al. High thiamine diphosphate level as a protective factor for Alzheimer's 
disease. Neurol Res. 2018;40(8):658-65. 
48. Zheng Y, Wu Q, Su F, Fang Y, Zeng J, Pei Z. The Protective Effect of Cantonese/Mandarin Bilingualism on the Onset of 
Alzheimer Disease. Dement Geriatr Cogn Disord. 2018;45(3-4):210-9. 
49. Zhang C, Li D, Wang X. Role of physical exercise type in olfactory deterioration in ageing. Rhinology. 2020;58(2):145-50. 
50. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association 
between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis 
Consortium. Jama. 1997;278(16):1349-56. 
51. Zuo X, Jia J. Promoter polymorphisms which modulate insulin degrading enzyme expression may increase susceptibility to 
Alzheimer's disease. Brain Res. 2009;1249:1-8. 
52. Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS, et al. Variants in the ATP-binding cassette transporter 
(ABCA7), apolipoprotein E 4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013;309(14):1483-92. 
53. Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M, et al. Genome-wide analysis of genetic loci 
associated with Alzheimer disease. JAMA. 2010;303(18):1832-40. 
54. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants 
at CLU and CR1 associated with Alzheimer's disease. Nat Genet. 2009;41(10):1094-9. 
55. Miyashita A, Koike A, Jun G, Wang LS, Takahashi S, Matsubara E, et al. SORL1 is genetically associated with late-onset 
Alzheimer's disease in Japanese, Koreans and Caucasians. PLoS One. 2013;8(4):e58618. 
56. Lv H, Jia L, Jia J. Promoter polymorphisms which modulate APP expression may increase susceptibility to Alzheimer's disease. 

25 
 
Neurobiol Aging. 2008;29(2):194-202. 
57. Delay C, Calon F, Mathews P, Hebert SS. Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect 
microRNA function. Mol Neurodegener. 2011;6:70. 
58. Liebsch F, Kulic L, Teunissen C, Shobo A, Ulku I, Engelschalt V, et al. Abeta34 is a BACE1-derived degradation intermediate 
associated with amyloid clearance and Alzheimer's disease progression. Nat Commun. 2019;10(1):2240. 
59. Vergallo A, Megret L, Lista S, Cavedo E, Zetterberg H, Blennow K, et al. Plasma amyloid beta 40/42 ratio predicts cerebral 
amyloidosis in cognitively normal individuals at risk for Alzheimer's disease. Alzheimers Dement. 2019;15(6):764-75. 
60. Bos I, Vos S, Verhey F, Scheltens P, Teunissen C, Engelborghs S, et al. Cerebrospinal fluid biomarkers of neurodegeneration, 
synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum. Alzheimers Dement. 2019;15(5):644-
54. 
61. Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Ohrfelt A, Andersson K, et al. Cerebrospinal fluid levels of the synaptic 
protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease. Alzheimers Dement. 2015;11(10):1180-
90. 
62. Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, et al. Serum neurofilament dynamics predicts neurodegeneration 
and clinical progression in presymptomatic Alzheimer's disease. Nat Med. 2019;25(2):277-83. 
63. Fortea J, Carmona-Iragui M, Benejam B, Fernandez S, Videla L, Barroeta I, et al. Plasma and CSF biomarkers for the diagnosis 
of Alzheimer's disease in adults with Down syndrome: a cross-sectional study. Lancet Neurol. 2018;17(10):860-9. 
64. Dhiman K, Blennow K, Zetterberg H, Martins RN, Gupta VB. Cerebrospinal fluid biomarkers for understanding multiple 
aspects of Alzheimer's disease pathogenesis. Cellular and molecular life sciences : CMLS. 2019;76(10):1833-63. 
65. Janelidze S, Mattsson N, Stomrud E, Lindberg O, Palmqvist S, Zetterberg H, et al. CSF biomarkers of neuroinflammation 
and cerebrovascular dysfunction in early Alzheimer disease. Neurology. 2018;91(9):e867-e77. 
66. Molinuevo JL, Ayton S, Batrla R, Bednar MM, Bittner T, Cummings J, et al. Current state of Alzheimer's fluid biomarkers. 
Acta Neuropathol. 2018;136(6):821-53. 
67. Zekanowski C, Styczynska M, Peplonska B, Gabryelewicz T, Religa D, Ilkowski J, et al. Mutations in presenilin 1, presenilin 2 
and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol. 2003;184(2):991-6. 
68. Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, et al. Early onset familial Alzheimer's disease: Mutation 
frequency in 31 families. Neurology. 2003;60(2):235-9. 
69. Lleo A, Blesa R, Queralt R, Ezquerra M, Molinuevo JL, Pena-Casanova J, et al. Frequency of mutations in the presenilin and 
amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol. 2002;59(11):1759-63. 
70. Gao Y, Ren RJ, Zhong ZL, Dammer E, Zhao QH, Shan S, et al. Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial 
Alzheimer's disease. Neurobiol Aging. 2019;77:154-7. 
71. Yagi R, Miyamoto R, Morino H, Izumi Y, Kuramochi M, Kurashige T, et al. Detecting gene mutations in Japanese Alzheimer's 
patients by semiconductor sequencing. Neurobiol Aging. 2014;35(7):1780 e1-5. 
72. An SS, Park SA, Bagyinszky E, Bae SO, Kim YJ, Im JY, et al. A genetic screen of the mutations in the Korean patients with 
early-onset Alzheimer's disease. Clin Interv Aging. 2016;11:1817-22. 
73. Jiao B, Tang B, Liu X, Xu J, Wang Y, Zhou L, et al. Mutational analysis in early-onset familial Alzheimer's disease in Mainland 
China. Neurobiol Aging. 2014;35(8):1957 e1-6. 
74. Krumm S, Kivisaari SL, Probst A, Monsch AU, Reinhardt J, Ulmer S, et al. Cortical thinning of parahippocampal subregions 
in very early Alzheimer's disease. Neurobiol Aging. 2016;38:188-96. 
75. Whittington A, Gunn RN. Amyloid Load: A More Sensitive Biomarker for Amyloid Imaging. Journal of nuclear medicine : 
official publication, Society of Nuclear Medicine. 2019;60(4):536-40. 
76. Oliveira F, Leuzy A, Castelhano J, Chiotis K, Hasselbalch SG, Rinne J, et al. Data driven diagnostic classification in Alzheimer's 
disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of 
Abeta species. NeuroImage Clinical. 2018;20:603-10. 
77. Veitch DP, Weiner MW, Aisen PS, Beckett LA, Cairns NJ, Green RC, et al. Understanding disease progression and improving 
Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 
2019;15(1):106-52. 
78. Chinese Dementia and Cognitive Impairment Diagnosis and Treatment Guidelines Writing Group, Chinese Medical Doctor 
Association Neurologist Branch Cognitive Impairment Disease Professional Committee, Jia JP. 2018 Chinese Dementia and 
Cognitive Impairment Guidelines (I): Dementia and its classification and diagnostic criteria. National Medical Journal of China. 
2018;98(13):965-70. 
79. Chinese Dementia and Cognitive Impairment Diagnosis and Treatment Guidelines Writing Group, Chinese Medical Doctor 
Association Neurologist Branch Cognitive Impairment Disease Professional Committee, Jia JP. 2018 China Dementia and 
Cognitive Impairment Guidelines (V): Diagnosis and Treatment of Mild Cognitive Impairment. National Medical Journal of China. 
2018;98(17):1294-301. 
80. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for 
the clinician. J Psychiatr Res. 1975;12(3):189-98. 

26 
 
81. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, 
MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695-9. 
82. Chinese Dementia and Cognitive Impairment Diagnosis and Treatment Guidelines Writing Group, Chinese Medical Doctor 
Association Neurologist Branch Cognitive Impairment Disease Professional Committee, Jia Jianping.2018 China Dementia and 
Cognitive Impairment Guidelines (III): Cognitive and functional evaluation of dementia. National Medical Journal of China. 
2018;98(15):1125-9. 
83. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 
1982;140:566-72. 
84. Maj M, Satz P, Janssen R, Zaudig M, Starace F, D'Elia L, et al. WHO Neuropsychiatric AIDS study, cross-sectional phase II. 
Neuropsychological and neurological findings. Arch Gen Psychiatry. 1994;51(1):51-61. 
85. Ricci M, Graef S, Blundo C, Miller LA. Using the Rey Auditory Verbal Learning Test (RAVLT) to differentiate alzheimer's 
dementia and behavioural variant fronto-temporal dementia. Clin Neuropsychol. 2012;26(6):926-41. 
86. Labovitz SS. Effect of physical layout in performance of the Trail Making Test. Psychological Assessment.7(2):220-1. 
87. Harrington RG. Factor Analysis of the Mainland Chinese Version of the Wechsler Adult Intelligence Scale (WAIS-RC) in a 
Brain-Damaged Sample. International Journal of Neuroscience. 1991;55(2-4):107-11. 
88. Perri R, Koch G, Carlesimo GA, Serra L, Fadda L, Pasqualetti P, et al. Alzheimer's disease and frontal variant of frontotemporal 
dementia-- a very brief battery for cognitive and behavioural distinction. J Neurol. 2005;252(10):1238-44. 
89. Melrose RJ, Harwood D, Khoo T, Mandelkern M, Sultzer DL. Association between cerebral metabolism and Rey-Osterrieth 
Complex Figure Test performance in Alzheimer's disease. J Clin Exp Neuropsychol. 2013;35(3):246-58. 
90. Dion C, Arias F, Amini S, Davis R, Penney D, Libon DJ, et al. Cognitive Correlates of Digital Clock Drawing Metrics in Older 
Adults with and without Mild Cognitive Impairment. J Alzheimers Dis. 2020. 
91. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: 
comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308-14. 
92. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression 
screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37-49. 
93. Mlinac ME, Feng MC. Assessment of Activities of Daily Living, Self-Care, and Independence. Arch Clin Neuropsychol. 
2016;31(6):506-16. 
94. Hackett K, Mis R, Drabick DAG, Giovannetti T. Informant Reporting in Mild Cognitive Impairment: Sources of Discrepancy 
on the Functional Activities Questionnaire. J Int Neuropsychol Soc. 2020:1-12. 
95. Hachinski V, Oveisgharan S, Romney AK, Shankle WR. Optimizing the Hachinski Ischemic Scale. Arch Neurol. 
2012;69(2):169-75. 
96. McMaster M, Kim S, Clare L, Torres SJ, D'Este C, Anstey KJ. Body, Brain, Life for Cognitive Decline (BBL-CD): protocol for a 
multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment. 
Clin Interv Aging. 2018;13:2397-406. 
97. Duan Y, Lu L, Chen J, Wu C, Liang J, Zheng Y, et al. Psychosocial interventions for Alzheimer's disease cognitive symptoms: 
a Bayesian network meta-analysis. BMC Geriatr. 2018;18(1):175. 
98. Minakawa EN, Wada K, Nagai Y. Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer's Disease. Int J Mol 
Sci. 2019;20(4). 
99. de la Rubia Orti JE, Garcia-Pardo MP, Drehmer E, Sancho Cantus D, Julian Rochina M, Aguilar MA, et al. Improvement of 
Main Cognitive Functions in Patients with Alzheimer's Disease after Treatment with Coconut Oil Enriched Mediterranean Diet: A 
Pilot Study. Journal of Alzheimer's disease : JAD. 2018;65(2):577-87. 
100. Serebrovska ZO, Serebrovska TV, Kholin VA, Tumanovska LV, Shysh AM, Pashevin DA, et al. Intermittent Hypoxia-Hyperoxia 
Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild 
Cognitive Impairment: A Pilot Study. Int J Mol Sci. 2019;20(21). 
101. Anderson-Hanley C, Barcelos NM, Zimmerman EA, Gillen RW, Dunnam M, Cohen BD, et al. The Aerobic and Cognitive 
Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): 
Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial. Front Aging Neurosci. 
2018;10:76. 
102. Groot C, Hooghiemstra AM, Raijmakers PG, van Berckel BN, Scheltens P, Scherder EJ, et al. The effect of physical activity on 
cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res Rev. 2016;25:13-23. 
103. McGurran H, Glenn JM, Madero EN, Bott NT. Prevention and Treatment of Alzheimer's Disease: Biological Mechanisms of 
Exercise. Journal of Alzheimer's disease : JAD. 2019;69(2):311-38. 
104. Haeger A, Costa AS, Schulz JB, Reetz K. Cerebral changes improved by physical activity during cognitive decline: A 
systematic review on MRI studies. Neuroimage Clin. 2019;23:101933. 
105. Fang R, Ye S, Huangfu J, Calimag DP. Music therapy is a potential intervention for cognition of Alzheimer's Disease: a mini-
review. Transl Neurodegener. 2017;6:2. 
106. Garcia-Casares N, Moreno-Leiva RM, Garcia-Arnes JA. [Music therapy as a non-pharmacological treatment in Alzheimer's 

27 
 
disease. A systematic review]. Rev Neurol. 2017;65(12):529-38. 
107. Lyu J, Zhang J, Mu H, Li W, Champ M, Xiong Q, et al. The Effects of Music Therapy on Cognition, Psychiatric Symptoms, 
and Activities of Daily Living in Patients with Alzheimer's Disease. Journal of Alzheimer's disease : JAD. 2018;64(4):1347-58. 
108. Cao X, Yao Y, Li T, Cheng Y, Feng W, Shen Y, et al. The Impact of Cognitive Training on Cerebral White Matter in Community-
Dwelling Elderly: One-Year Prospective Longitudinal Diffusion Tensor Imaging Study. Sci Rep. 2016;6:33212. 
109. Soldan A, Pettigrew C, Cai Q, Wang J, Wang MC, Moghekar A, et al. Cognitive reserve and long-term change in cognition 
in aging and preclinical Alzheimer's disease. Neurobiol Aging. 2017;60:164-72. 
110. Rossi Dare L, Garcia A, Alves N, Ventura Dias D, de Souza MA, Mello-Carpes PB. Physical and cognitive training are able to 
prevent recognition memory deficits related to amyloid beta neurotoxicity. Behav Brain Res. 2019;365:190-7. 
111. Zucchella C, Sinforiani E, Tamburin S, Federico A, Mantovani E, Bernini S, et al. The Multidisciplinary Approach to Alzheimer's 
Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment. Front Neurol. 2018;9:1058. 
112. Liu D, Cheng G, An L, Gan X, Wu Y, Zhang B, et al. Public Knowledge about Dementia in China: A National WeChat-Based 
Survey. Int J Environ Res Public Health. 2019;16(21). 
113. Gao SS. Application of synchronous education for family members in health education for patients with Alzheimer's disease. 
Chinese Journal of Convalescent Medicine. 2013(03):86-7. 
114. Wen Y. Nursing and health education of outpatient senile dementia. The 8th National Elderly Nursing Academic Exchange 
and Special Lecture Conference Paper Collection; 2005. 
115. Gao QH. Health education for senile dementia. Chinese medicine consultation. 2010;002(014):195. 
116. Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and 
cross-validation. Psychol Med. 1994;24(1):145-53. 
117. Berg L, Miller JP, Baty J, Rubin EH, Morris JC, Figiel G. Mild senile dementia of the Alzheimer type. 4. Evaluation of 
intervention. Ann Neurol. 1992;31(3):242-9. 
 
 

28 
 
14. Appendix 
Appendix 1 Mini-mental state examination (MMSE) (80) 
Activity 
                                                               Score 
 
 
ORIENTATION – one point for each answer 
  Ask: “What is the: (year)(season)(date)(day)(month)?”                         _______ 
  Ask: “Where are we: (state)(county)(town)(hospital)(floor)?”                    _______ 
 
 
REGISTRATION – score 1,2,3 points according to how many are repeated  
  Name three objects: Give the patient one second to say each. 
  Ask the patient to: repeat all three after you have said them.  
  Repeat them until the patient learns all three.                                 _______ 
 
ATTENTION AND CALCULATION – one point for each correct subtraction  
  Ask the patient to: begin from 100 and count backwards by 7. 
  Stop after 5 answers. (93, 86, 79, 72, 65)                                    _______ 
 
 
RECALL – one point for each correct answer 
  Ask the patient to: name the three objects from above.                          _______ 
 
 
LANGUAGE 
Ask the patient to: identify and name a pencil and a watch. (2 points)                _______ 
Ask the patient to: repeat the phrase “No ifs, ands, or buts.” (1 point)                _______ 
Ask the patient to: “Take a paper in your right hand, fold it in half, 
 and put it on the floor “ (1 point for each task completed properly)                 _______ 
Ask the patient to: read and obey the following: “Close your eyes.” (1 point)          _______ 
Ask the patient to: write a sentence. (1 point)                                   _______ 
Ask the patient to: copy a complex diagram of two interlocking pentagons. (1 point)    _______ 
 
 
 
                                                   
 
 
 
                                            TOTAL (0-30):  _______ 
 
 
 

29 
 
Appendix 2 Montreal cognitive assessment(MoCA) (81) 
Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses 
different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual 
thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; 
a score of 26 or above is considered normal. 
 
contents 
Administration and Scoring Instructions  
score 
2.1 
Alternating Trail 
Making 
Administration: The examiner instructs the subject: "Please draw a line, going from a number to a 
letter in ascending order. Begin here [point to (1)] and draw a line from 1 then to A then to 2 and 
so on. End here [point to (E)]." 
Scoring: Allocate one point if the subject successfully draws the following pattern: 1 −A- 2- B- 3- 
C- 4- D- 5- E, without drawing any lines that cross. Any error that is not immediately self-
corrected earns a score of 0. 
 
2.1 score□ 
2.2 
Visuoconstructional 
Skills (Cube) 
Administration: The examiner gives the following instructions, pointing to the cube: “Copy this 
drawing as accurately as you can, in the space below”. 
Scoring: One point is allocated for a correctly executed drawing. 
• Drawing must be three-dimensional 
• All lines are drawn 
• No line is added 
• Lines are relatively parallel and their length is similar (rectangular prisms are accepted) 
A point is not assigned if any of the above-criteria are not met. 
 
 
2.2 score□ 
 
2.3 
Visuoconstructional 
Skills (Clock) 
Administration: Indicate the right third of the space and give the following instructions: “Draw a 
clock. Put in all the numbers and set the time to 10 past 11”. 
Scoring: One point is allocated for each of the following three criteria: 

30 
 
• Contour (1 pt.): the clock face must be a circle with only minor distortion acceptable (e.g., slight 
imperfection on closing the circle); 
• Numbers (1 pt.): all clock numbers must be present with no additional numbers; numbers must 
be in the correct order and placed in the approximate quadrants on the clock face; Roman 
numerals are acceptable; numbers can be placed outside the circle contour; 
• Hands (1 pt.): there must be two hands jointly indicating the correct time; the hour hand must be 
clearly shorter than the minute hand; hands must be centered within the clock face with their 
junction close to the clock center. 
A point is not assigned for a given element if any of the above-criteria are not met.  
At the same time, the score is given by the 15-point method (see table below), not counting the 
total score. 
 
Contents 
Yes 
No 
score 
1 
Shape similar to the clock 
1 
0 
 
2 
Round circumference 
1 
0 
 
3 
Diameter >2.5 cm (if the first painting is small, encourage it to 
draw larger) 
1 
0 
 
4 
All the numbers are inside the circle 
1 
0 
 
5 
First locate 12,6,3,9 
1 
0 
 
6 
The numbers are arranged at regular intervals (symmetrically 
arranged on a 12-6 axis). If it is so, skip the 7th question 
2 
0 
 
7 
If there is a spatial alignment error, it can be corrected (with 
traces of alteration) 
1 
0 
 
8 
Only Arabic numerals 
1 
0 
 
9 
Only the Arabic numerals 1-12 appear 
1 
0 
 
10 
1-12 appears in sequence, no omission or misalignment 
1 
0 
 
11 
Only 2 pointers 
1 
0 
 
12 
The pointer is like an arrow 
1 
0 
 
13 
The hour hand is between 11 and 12 
1 
0 
 
14 
The minute hand is longer than the hour hand 
1 
0 
 
15 
There is no problem under the column 
1 
0 
 
 
1)The minute hand points to 10 o'clock 
 
 
 
 
2)Write the words 11:10 
 
 
 
 
3)Extra pointer or circle 
 
 
 
 
4)Any letters, words or diagrams appear 
 
 
 
 
5)Any extra lines appear below the circle 
 
 
 
2.3 score □——3-point 
method 
2.3.1 score□□——15-point method 
2.4 
Naming 
Administration: Beginning on the left, point to each figure and say: “Tell me the 
name of this animal”. 
Scoring: One point each is given for the following responses: (1) lion (2) giraffe 
(3) camel or dromedary. 
2.4 score□ 

31 
 
 
2.5 
Memory 
Administration: The examiner reads a list of 5 words at a rate of one per second, giving the 
following instructions: “This is a memory test. I am going to read a list of words that you will 
have to remember now and later on. Listen carefully. When I am through, tell me as many words 
as you can remember. It doesn’t matter in what order you say them”. Mark a check in the 
allocated space for each word the subject produces on this first trial. When the subject indicates 
that (s) he has finished (has recalled all words), or can recall no more words, read the list a second 
time with the following instructions: “I am going to read the same list for a second time. Try to 
remember and tell me as many words as you can, including words you said the first time.” Put a 
check in the allocated space for each word the subject recalls after the second trial. 
At the end of the second trial, inform the subject that (s)he will be asked to recall these words 
Again by saying, “I will ask you to recall those words again at the end of the test.” 
Scoring: No points are given for Trials One and Two. 
 
Face 
Velvet 
School 
Daisy 
Red 
First 
 
 
 
 
 
Second 
 
 
 
 
 
2.6 
Forward Digit Span 
Give the following instruction: “I am going to say some numbers and when I am 
through, repeat them to me exactly as I said them”. Read the five number 
sequence at a rate of one digit per second. 
Scoring: Allocate one point for each sequence correctly repeated. 
21854 [  ] 
2.6 score□ 
2.7 
Backward Digit Span 
Administration: Give the following instruction: “Now I am going to say some 
more numbers, but when I am through you must repeat them to me in the 
backwards order.” Read the three number sequence at a rate of one digit per 
second. 
Scoring: Allocate one point for each sequence correctly repeated, (N.B.: the 
correct response for the backwards trial is 2-4-7). 
742 [  ] 
2.7 score□ 
2.8 
Vigilance 
Administration: The examiner reads the list of numbers at a rate of one per 
second, after giving the following instruction: “I am going to read a sequence of 
numbers. Every time I say the number 1, knock the table once. If I say a different 
letter, do not knock the table”. 
Scoring: Give one point if there is zero to one errors (an error is a knock on a 
wrong number or a failure to knock on number 1). 
52139411806215194511141905112 [  ] 
2.8 score□ 

32 
 
2.9 
Serial 7s 
(Refer to the MMSE 
result score) 
Administration: The examiner gives the following instruction: “Now, I will ask 
you to count by subtracting seven from 100, and then, keep subtracting seven 
from your answer until I tell you to stop.” Give this instruction twice if necessary. 
Scoring: This item is scored out of 3 points. Give no (0) points for no correct 
subtractions, 1 point for one correction subtraction, 2 points for two-to-three 
correct subtractions, and 3 points if the participant successfully makes four or five 
correct subtractions. Count each correct subtraction of 7 beginning at 100. Each 
subtraction is evaluated independently; that is, if the participant responds with an 
incorrect number but continues to correctly subtract 7 from it, give a point for 
each correct subtraction. For example, a participant may respond “92 – 85 – 78 – 
71 – 64” where the “92” is incorrect, but all subsequent numbers are subtracted 
correctly. This is one error and the item would be given a score of 3. 
[  ]93   [  ]86   [  ]79   [  ]72   [  ]65 
2.9 score□ 
2.10 
Sentence repetition 
Administration: The examiner gives the following instructions: “I am going to 
read you a sentence. Repeat it after me, exactly as I say it [pause]: I only know 
that John is the one to help today.” Following the response, say: “Now I am going 
to read you another sentence. 
Repeat it after me, exactly as I say it [pause]: The cat always hid under the couch 
when dogs were in the room.” 
Scoring: Allocate 1 point for each sentence correctly repeated. Repetition must be 
exact. Be alert for errors that are omissions (e.g., omitting "only", "always") and 
substitutions/additions (e.g., "John is the one who helped today;" substituting 
"hides" for "hid", altering plurals, etc.). 
I only know that John is the one to help today. [  ] 
The cat always hid under the couch when dogs were in the room. [  ] 
2.10score□ 
2.11 
Verbal fluency 
Administration: "Please tell as many animals as you can, as soon as possible. The 
time is 1 minute, are you ready? Start." Stop after one minute. 
Scoring: If the subject names ≥11 within 1 minute, score 1 point. At the same 
time, record the examiner's answer as much as possible. Deified animals such as 
dragons, phoenixes, and unicorns are also correct. 
please record ： 
2.11.1(0-15 s)                                                      
2.11.2(16-30 s)                                                       
2.11.3(31-45 s)                                                  
2.11.4(46-60 s)                                          
[  ]        ( N≥11 words) 
2.11score□ 
2.12 
Abstraction 
Administration: The examiner asks the subject to explain what each pair of words 
has in common, starting with the example: “Tell me how an orange and a banana 
are alike”. If the subject answers in a concrete manner, then say only one 
additional time: “Tell me another way in which those items are alike”. If the 
subject does not give the appropriate response (fruit), say, “Yes, and they are also 
both fruit.” Do not give any additional instructions or clarification. After the 
practice trial, say: “Now, tell me how a train and a bicycle are alike”. Following 
the response, administer the second trial, saying: “Now tell me how a ruler and a 
watch are alike”. 
Do not give any additional instructions or prompts. 
Scoring: Only the last two item pairs are scored. Give 1 point to each item pair 
2.12score□ 

33 
 
correctly answered. The following responses are acceptable:  
[  ] Train-bicycle： Means of transportation, means of travelling, you take trips 
in both; 
[  ] Ruler-watch ： Measuring instruments, used to measure. 
The following responses are not acceptable: Train-bicycle = they have wheels; 
Ruler-watch = they have numbers. 
2.13 
Delayed recall 
Administration: The examiner gives the following instruction: “I read some words 
to you earlier, which I asked you to remember. Tell me as many of those words as 
you can remember.” Make a check mark ( √ ) for each of the words correctly 
recalled spontaneously without any cues, in the allocated space. 
Scoring: Allocate 1 point for each word recalled freely without any cues. 
Following the delayed free recall trial, prompt the subject with the semantic 
category cue provided below for any word not recalled. Make a check mark ( √ ) 
in the allocated space if the subject remembered the word with the help of a 
category or multiple-choice cue. Prompt all non-recalled words in this manner. If 
the subject does not recall the word after the category cue, give him/her a multiple 
choice trial, using the following example instruction, “Which of the following 
words do you think it was, NOSE, FACE, or HAND?”  
Use the following category and/or multiple-choice cues for each word, when 
appropriate: 
 
Face 
Velvet 
School 
Daisy 
Red 
No prompt 
 
 
 
 
 
category 
cue 
part of 
the body 
type of 
fabric 
type of 
building 
type of 
flower 
a colour 
 
 
 
 
 
multiple 
choice 
nose, 
face, 
hand 
denim, 
cotton, 
velvet 
church, 
school, 
hospital 
rose, 
daisy,  
tulip 
red, blue, 
green 
 
 
 
 
 
Scoring: No points are allocated for words recalled with a cue. A cue is used for 
clinical information purposes only and can give the test interpreter additional 
information about the type of memory disorder. For memory deficits due to 
retrieval failures, performance can be improved with a cue. For memory deficits 
due to encoding failures, performance does not improve with a cue. 
2.13score□ 
2.14 
Orientation 
Administration: The examiner gives the following instructions: “Tell me the date 
today”. If the subject does not give a complete answer, then prompt accordingly 
by saying: “Tell me the [year, month, exact date, and day of the week].” Then 
say: “Now, tell me the name of this place, and which city it is in.” 
Scoring: Give one point for each item correctly answered. The subject must tell 
the exact date and the exact place (name of hospital, clinic, office). No points are 
allocated if subject makes an error of one day for the day and date. 
[  ] Date [  ] Month [  ] Year [  ] Day [  ] Place [  ] City 
2.14score□ 
2.15 
Total score 
 
2.15score□
□ 
TOTAL SCORE: Sum all sub scores listed on the right-hand side. Add one point for an individual who has 12 years or fewer of formal 
education, for a possible maximum of 30 points. 
A final total score of 26 and above is considered normal.  
 
 

34 
 
Appendix 3 Neuropsychiatric Inventory (NPI-Q) (91) 
Scoring levels with example definitions for the NPI-Q 
Frequency of occurrence (1~4) 
1. Occasionally: less than once per week 
2. Often: about once per week 
3. Frequently: several times per week but less than every day 
4. Very frequently: once or more per day 
Severity of behavior (1~3) 
1. Mild: mildly distressing to the patient and not a major problem 
2. Moderate: distressing to the patient but easily overcome by reassurance 
3. Marked: distressing to the patient and difficult to redirect or deal with 
Distress to you (0~5) 
0. Not at all 
1. Minimally: rarely distressing and easily tolerated 
2. Mildly: occasionally distressing, but not a significant problem 
3. Moderately: somewhat distressing and problematic, but usually tolerable 
4. Severely: very distressing and difficult to cope with 
5. Very severely or extremely: markedly distressing and extremely difficult to cope with 
The score for each item is calculated by multiplying the frequency by the intensity; and the total score for the NPI is calculated 
by adding the scores of all symptoms. 
Thus, scores may range from 0 to a maximum of 144, where the higher the score, the more severe the psychopathology. 
 Summary table for NPI-Q scores. 
Symptom 
FrequencySeverity
Total 
(frequency × 
severity)  
Distress 
to you 
3.1 Delirium  
Does the patient have a false idea, such as thinking that 
someone else has stolen his/her things? Do you suspect that 
someone is harming him? 
 
 
 
 
3.2 Hallucinations  
Does the patient have hallucinations such as visual 
hallucinations or auditory hallucinations? See or hear something 
or sound that doesn't exist? Talking to someone who doesn't 
actually exist? 
 
 
 
 
3.3 Agitation/aggression  
Does the patient often refuse help from others? 
Unmanageable? Stubborn? Shouting at others? Snoring others? 
 
 
 
 
3.4 Depression/dysphoria  
Does the patient show grief or express a depression? 
 
 
 
 
3.5 Anxiety  
Is it uncomfortable after the patient is separated from the 
caregiver? Does the patient have mental stress such as shortness 
of breath, sigh, can't relax or feel nervous? 
 
 
 
 
3.6 Joy/euphoria  
Is the patient too happy and feeling too good? Feeling 
humorous and laughing at things that others are not interesting 
about? Joy that doesn't match the situation? 
 
 
 
 
3.7 Apathy  
Did the patient lose interest in activities that were 
previously of interest? Indifferent to other people's activities and 
plans? 
 
 
 
 
3.8 Disinhibition  
Does the patient lose self-control, such as talking to 
strangers like an acquaintance? Or talk regardless of the feelings 
of others? 
 
 
 
 
3.9 Irritability/lability 
Does the patient show impatience or crazy behavior? Can't 
bear the delay? Can't wait patiently for the planned activities? 
 
 
 
 
3.10 Abnormal motor 
behaviour 
Does the patient repeat nonsense activities, such as turning 
around a house, playing with buttons, bandaging with a rope, 
etc.? Or other repetitive activities? 
 
 
 
 
3.11 Sleep disorders 
Does the patient wake others up at night? Get up early in 
the morning? Frequent snoring during the day? 
 
 
 
 
3.12 Eating disorders  
Does the patient's weight decrease or increase? Do you like 
the taste of food changes? 
 
 
 
 

35 
 
3.13 Total score 
 
 

36 
 
Appendix 4 Geriatric Depression Scale (GDS) (92) 
 
Please answer “yes” or “no” to the following questions in regards to how you have been feeling recently. 
 
 
Yes 
No 
4.1 Are you basically satisfied with your life?  
 
 
4.2 Have you dropped many of your activities and interests? 
 
 
4.3 Do you feel that your life is empty?  
 
 
4.4 Do you often get bored?  
 
 
4.5 Are you hopeful about the future? 
 
 
4.6 Are you bothered by thoughts you can’t get out of your head? 
 
 
4.7 Are you in good spirits most of the time?  
 
 
4.8 Are you afraid that something bad is going to happen to you? 
 
 
4.9 Do you feel happy most of the time? 
 
 
4.10 Do you often feel helpless?  
 
 
4.11 Do you often get restless and fidgety? 
 
 
4.12 Do you prefer to stay at home, rather than going out and doing new things? 
 
 
4.13 Do you frequently worry about the future?  
 
 
4.14 Do you feel you have more problems with memory than most? 
 
 
4.15 Do you think it is wonderful to be alive now? 
 
 
4.16 Do you often feel downhearted and blue? 
 
 
4.17 Do you feel pretty worthless the way you are now? 
 
 
4.18 Do you worry a lot about the past? 
 
 
4.19 Do you find life very exciting?  
 
 
4.20 Is it hard for you to get started on new projects? 
 
 
4.21 Do you feel full of energy? 
 
 
4.22 Do you feel that your situation is hopeless? 
 
 
4.23 Do you think that most people are better off than you are? 
 
 
4.24 Do you frequently get upset over little things? 
 
 
4.25 Do you frequently feel like crying?  
 
 
4.26 Do you have trouble concentrating? 
 
 
4.27 Do you enjoy getting up in the morning?  
 
 
4.28 Do you prefer to avoid social gatherings? 
 
 
4.29 Is it easy for you to make decisions? 
 
 
4.30 Is your mind as clear as it used to be? 
 
 
 
 
 
 
 
 
 

3 7 
 
A p pe n di x 5: M o difie d H a c hi ns ki isc he mic sc ale ( m -HI S)  ( 9 5) 
 
 
Fe at ure  
Ye s  
N o  
H 1   
A br u pt o nset  
�2  
�0  
H 2   
St e p wis e d et eri or ati o n  
�1  
�0  
H 3  
S o matic c o m plai nt  
�1  
�0  
H 4  
E m oti o n al i n c o nti n e n ce  
�1  
�0  
H 5  
Hist or y or prese n ce of h y p erte nsi o n  
�1  
�0  
H 6  
Hist or y of str o k es  
�2  
�0  
H 7  
F ocal n e ur ol o gical s y m pt o ms  
�2  
�0  
H 8              
F ocal n e ur ol o gical si g ns  
�2  
�0  
H 9  
T otal (atte nti o n：sc ore ≥4  ca n b e c h osen ) 
|____|.|____| 
 
 
 
 

38 
 
Appendix 6: World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA 
AVLT (84) 
On each of 3 learning trials, 15 unrelated words (all nouns) are presented orally at the rate of one word per second and immediate 
free recall of the words is elicited. The number of correctly recalled words on each trial is recorded. Following a 30-minute delay filled 
with unrelated testing, free recall of the original 15 word list is elicited. In cued recall, the experimenter prompts the subjects with the 
word category. Finally, a yes/no recognition test is administered which consists of the original 15 words and 15 randomly interspersed 
distracter words. The number of target “hits” and false positive responses are recorded.  
 
 
 
Text 1 
Text 2 
Text 3 
 
Delay recall 
arm 
 
 
 
arm 
 
cat 
 
 
 
cat 
 
axe 
 
 
 
axe 
 
bed 
 
 
 
bed 
 
airplane 
 
 
 
airplane 
 
ear 
 
 
 
ear 
 
dog 
 
 
 
dog 
 
hammer 
 
 
 
hammer 
 
chair 
 
 
 
chair 
 
car 
 
 
 
car 
 
eyes 
 
 
 
eyes 
 
horse 
 
 
 
horse 
 
knife 
 
 
 
knife 
 
clock 
 
 
 
clock 
 
bicycle 
 
 
 
bicycle 
 
 
 
Item category 
Record 
a body part 
□ arm 
□ ear 
□ eyes 
animal 
□ cat 
□ dog 
□ horse 
tools 
□ axe 
□ hammer 
□ knife 
furniture 
□ bed 
□ chair 
□ clock 
vehicle 
□ airplane 
□ car 
□ bicycle 
 
 
 
 
 
Yes 
No 
 
Yes 
No 
mirror 
 
 
mouse 
 
 
hammer 
 
 
tree 
 
 

39 
 
knife 
 
 
arm 
 
 
candle 
 
 
nose 
 
 
motorbike 
 
 
sun 
 
 
axe 
 
 
truck 
 
 
clock 
 
 
eyes 
 
 
chair 
 
 
fish 
 
 
airplane 
 
 
ear 
 
 
tortoise 
 
 
bicycle 
 
 
horse 
 
 
snake 
 
 
thigh 
 
 
bench 
 
 
dog 
 
 
bus 
 
 
table 
 
 
bed 
 
 
cat 
 
 
car 
 
 
 
 
 
 
 
 

40 
 
Appendix 7: Trail making test (TMT) (86) 
Part A 
Practice test 
Administration: The following are some circles with numbers in the circle. I would like to ask you to connect in the order of 1-2-
3... with a pen. Note: Do not leave the pen tip away from the paper and the line drawn must pass through the graphic. If I am wrong, I 
will point out that you need to go back and paint again. Let us give it a try now. The sooner you paint, the better. Are you ready? Start! 
Note: The following is a practice test, not scored. Correct every time you make a mistake, and tell the correct connection method, while 
actively encouraging. 
 
 
 

41 
 
Actual test 
Administration: There is a similar circle diagram here, please connect it again as above. Please note that the faster you draw, the 
better. Do not leave the pen tip and the lines drawn must pass through the graphic. Start here (pointing to the starting point) until here 
(pointing to the end). Ready? Start. (time) 
 
 
 
 
7.1.1 All digital completion time (0-150) seconds (if 150 seconds is not completed, record 150) 
7.1.2 Number of errors(0-25; 88=Not applicable) 
7.1.3 Correct number (0-25; 88=Not applicable) 
End 
Begin 

42 
 
Part B 
Administration: The following are 1-13 white circle numbers and 1-12 black circle numbers. They are also scattered. Please 
connect them in order, i.e. white circle 1 - black circle 1 - white circle 2 - black circle 2... Note: Do not leave the pen tip away from the 
paper and the line drawn must pass through the graphic. If I am wrong, I will point out that you need to go back and paint again. Let us 
give it a try now. The sooner you paint, the better. Are you ready? Start! 
Practice test 
 
 
End   
Begin   

43 
 
Actual test 
 
 
 
 
 
 
 
 
 
 
 
 
7.2.1 All digital completion time (0-300) seconds (if 300 seconds is not completed, record 300) 
7.2.2 Number Sequence Error Number (0-25; 88=Not applicable) 
7.2.3 Correct number of lines (0-24; 88=Not applicable) 
Begin  
End  

44 
 
Appendix 8: Digit span test (DST) (87) 
This task consists of two parts. Digits forward is administered first and requires the repetition of digits in the same order presented, 
while in digits backwards participants must repeat digits in an inverse or backwards order. Text 2 is administered even if the participant 
fails in Text 1. 
 
Text 1 
 
Text 2 
3 
5-8-2 
3 
6-9-4 
4 
6-4-3-9 
4 
7-2-8-6 
5 
4-2-7-3-1 
5 
7-5-8-3-6 
6 
6-1-9-4-7-3 
6 
3-9-2-4-8-7 
7 
5-9-1-7-4-2-8 
7 
4-1-7-9-3-8-6 
8 
5-8-1-9-2-6-4-7 
8 
3-8-2-9-5-1-7-4 
9 
2-7-5-8-6-2-5-8-4 
9 
7-1-3-9-4-2-5-6-8 
10 
5-2-7-4-9-1-3-7-4-6 
10 
4-7-2-5-9-1-6-2-5-3 
Digit span 
 
 
 
 
Text 1 
 
Text 2 
2 
2-4 
2 
5-8 
3 
6-2-9 
3 
4-1-5 
4 
3-2-7-9 
4 
4-9-6-8 
5 
1-5-2-8-6 
5 
6-1-8-4-3 
6 
5-3-9-4-1-8 
6 
7-2-4-8-5-6 
7 
8-1-2-9-3-6-5 
7 
4-7-3-9-1-2-8 
8 
9-4-3-7-6-2-5-8 
8 
7-2-8-1-9-6-5-3 
Backwards digit span 
 
 

45 
 
Appendix 9: Boston naming test (BNT) (88) 
Administration: "I will show you some pictures now, please tell me what these pictures are." 
If the tester fails to answer the answer, he is prompted: For example, "This is (plant), is there another name?" 
If you still can't answer, then three answers are given in order to let the tester choose. Remember to record every answer of the 
testier, whether correct or not (only calculate the score of spontaneous naming: correct = 1, answer = 0). 
 
Picture 
Answer 
(yes = 1; 
wrong = 
0) 
If wrong, 
specific 
record 
If the answer 
is wrong, 
prompt 
Answer 
(yes = 1; 
wrong = 0) 
If wrong, 
specific 
record 
If the prompt still answers the error, please 
select (circle the specific choice) 
9.1 
2. Tree 
  
 
plant 
 
  
Peach blossom Tree 
Fireworks 
9.2 
3. Pen 
  
 
Used for 
writing 
 
  
straw 
Original ball 
pen 
pen 
9.3 
6. Scissors 
  
 
tool 
 
  
Scissors 
clamp 
Spoon 
9.4 
8. Flowers 
  
 
plant 
 
  
Vegetables 
straw hat 
flower 
9.5 
9. Saw 
  
 
Woodworkin
g equipment 
 
  
Machine gun 
Saw 
Knife 
9.6 
12. Broom 
  
 
Used for 
cleaning 
 
  
Mop 
Writing 
brush 
Broom 
9.7 
*14. Mushroom
  
 
food 
 
  
Mushroom 
Cauliflower umbrella 
9.8 
15. Hangers 
  
 
Inside the 
wardrobe 
 
  
roof 
hanger 
hook 
9.9 
16. Wheelchair 
  
 
Patient use 
 
  
Executive 
chair 
trolley 
wheelchair 
9.10 
17. Camel 
  
 
animal 
 
  
camel 
mountain 
Cattle 
9.11 
21 racquet 
  
 
Sporting 
goods 
 
  
Ping pong 
paddle 
racquet 
mirror 
9.12 
22. Snail 
  
 
animal 
 
  
snails  
Squid 
scallop 
9.13 
24. Seahorse 
  
 
Marine life 
 
  
hook 
abalone 
Seahorse 
9.14 
25. Darts 
  
 
Used to 
throw 
 
  
Target 
Darts 
rocket 
9.15 
30. Harmonica 
  
 
Musical 
instrument 
 
  
Harmonica 
Air 
conditioner 
box 
9.16 
31. Rhinoceros 
  
 
animal 
 
  
Canned knife 
hippo 
rhinoceros 
9.17 
33. Igloo 
  
 
Used to live 
 
  
Ice house 
Grass house grave 
9.18 
36. Cactus 
  
 
plant 
 
  
Iron tree 
cactus 
cross 
9.19 
37 escalator 
  
 
Use up and 
down 
 
  
Sliced bread  
Slide 
escalator 
9.20 
38. Harp 
  
 
Musical 
instrument 
 
  
harp 
floor lamp 
piano 
9.21 
42. Stethoscope 
  
 
Doctor 
 
  
Earphone 
Stethoscope sphygmomano
meter 
9.22 
43. Pyramid 
  
 
In Egypt 
 
  
Zongzi 
Sphinx 
pyramid 
9.23 
46. Funnel 
  
 
Pour water 
 
  
Funnel 
Ice cream 
cones 
Pump 
9.24 
47. Accordion 
  
 
Musical 
instrument 
 
  
Harmonica 
accordion 
Blinds 
9.25 
50. Compass 
  
 
painting 
 
  
Cotton pliers 
ruler 
Compasses 
9.26 
52. Tripod 
  
 
For 
photography 
 
  
tripod  
Mechanical 
arm 
easel 
9.27 
54. tongs 
  
 
Appliance 
 
  
Spatula 
tongs 
canoe 
9.28 
57. 
Flower
shed/ trellis 
  
 
Park has 
 
  
Flower shed/ 
trellis 
trash can  
network 
9.29 
59. Protractor 
  
 
stationery 
 
  
Pound scale 
Triangle ruler Protractor 
9.30 
60. Abacus 
  
 
Counting 
 
  
Calculator 
Abacus 
Curtain 
Total 
9.31 
 
 
9.32 
 
 
9.33 
 
 
 
 
 

46 
 
Appendix 10: Activities of daily living (ADL) (93) 
Ask the insider to rate the following functions of the patient based on the information provided (assessed according to the level of 
intelligence). 
Rating 
Instrumental Daily Living Ability Scale (LADH) Scoring Project 
1 
Ability to use the phone 
 
□1、take the initiative to operate the phone - check the number, dial, etc. 
 
□2、can dial a few familiar numbers 
 
□3、can answer the phone but not dial the phone 
 
□4、cannot use the telephone 
2 
Shopping 
 
□1、independently handle all shopping needs 
 
□2、a small amount of shopping independently 
 
□3、need to accompany on any purchase 
 
□4、completely unable to shopping 
3 
Cooking 
 
□1、independently plan, prepare and make the right amount of meal 
 
□2、if the raw materials can be prepared to prepare enough meal 
 
□3、heating, serving or cooking, or cooking but not keeping the right amount 
 
□4、Need to prepare the meal and do it well 
4 
Hosting housework 
 
□1、independently host housework or occasionally need help (such as heavy work needs 
family help) 
 
□2、do daily light physical housework such as washing dishes, making beds 
 
□3、do daily light physical housework but cannot maintain an acceptable level of 
cleanliness 
 
□4、all housework needs help 
 
□5、do not participate in any housework 
5 
Washing 

47 
 
 
□1、can complete a personal bath 
 
□2、wash small pieces of clothing - wash socks, etc.  
 
□3、all washing must be done by others 
6 
Transportation 
 
□1、independent public transport or driving a car 
 
□2、travel by taxi, but no bus 
 
□3、take the bus when accompanied by others 
 
□4、can only travel by taxi or car with the help of others 
 
□5、no travel at all 
7 
Responsibility for the medical care 
 
□1、can take medicine seriously according to the correct time and dose 
 
□2、if you prepare for each dose, you can take medicine 
 
□3、you can't prepare your own medicine 
8 
Financial ability 
 
□1、independently handle finance (budget, write checks, pay rent, bills, go to the bank), 
collect and maintain income channels 
 
□2、manage daily shopping, but need help in banking affairs and big shopping, etc. 
 
□3、can't handle finance 
9 IADL total score 
Rating 
Somatic Self-care Ability Scale (PSUS) Scoring Project 
10 
Bowel and bladder function at the toilet, 
 
□1、in the bathroom can be completely self-care, no incontinence 
 
□2、need to be reminded of self-cleaning, or need help, or a small number of accidents (at 
least once a week) 
 
□3、dirty or wet during sleep, more than once a week 
 
□4、dirty or wet when awake, more than once a week 
 
□5、incontinence 

48 
 
11 
Eating 
 
□1、no need to help when eating 
 
□2、eating a small amount of time to eat and/or need to prepare special food, or need help 
after cleaning after meals 
 
□3、need moderate help for meal, and it is not neat 
 
□4、all meals need a lot of help 
 
□5、can't eat at all, and resist feeding by others 
12 
Dressing 
 
□1、wear clothes, undress, and choose clothes from your wardrobe 
 
□2、wearing clothes and undressing, need a small amount of help 
 
□3、need moderate help in dressing and choosing clothes 
 
□4、need more help in wearing clothes, but with the help of others 
 
□5、can't wear clothes at all, and it is against the help of others 
13 
Carding (tidy, hair, nails, hands, face, clothes) 
 
□1、always dressed neatly, properly decorated, no need to help 
 
□2、can properly decorate themselves, occasionally need a small amount of help, such as 
repairing beard 
 
□3、need moderate or reasonable help or guidance in combing 
 
□4、all combing matters need help, but can be kept neat after others help 
 
□5、actively oppose the efforts of others to help sort out 
14 
Walking 
 
□1、walk to the venue or urban area 
 
□2、Walk in the residential area or walk near a street 
 
□3、walking needs help (choose 1) a() cane, b() walker, c() wheelchair 
 
□1-In and out without help 

49 
 
 
□2-In and out need help 
 
□4、don’t need to sit in a chair or a wheelchair, but you can’t push it yourself without 
help 
 
□5、more than half of the time bedridden 
15 
Bathing 
 
□1、take a bath (bath, shower, bath), no need to help 
 
□2、need help when getting in and out of the tub 
 
□3、only wash your face and hands, cannot wash other parts of the body 
 
□4、cannot take a bath, but with others to bathe him 
 
□5、cannot take a bath, and resist efforts to keep him clean 
16 BADL total score 
17 ADL total score (IADL+BADL) 
The total score below 16 is completely normal, and greater than 16 points have different degrees of functional decline, up to 64 
points. The single item is divided into 1 normal, 2 to 4 is divided into functional decline, where there are 2 or more than ≥ 3 points, or 
the total score is ≥ 22 points, there are obvious obstacles to function  
 
 

50 
 
Appendix 11: Clinical Dementia Rating (CDR) (83) 
This is a semi-structured interview. Please ask all of these questions. Ask any additional questions necessary to determine the 
subject’s CDR. Please note information from the additional questions. 
Memory Questions for Informant: 
 
1.  Does he/she have a problem with his/her memory or thinking? 1a. If    
   yes, is this a consistent problem (as opposed to inconsistent)? 
2.  Can he/she recall recent events? 
3.  Can he/she remember a short list of items (shopping)? 
4.  Has there been some decline in memory during the past year? 
5.  Is his/her memory impaired to such a degree that it would have 
 
Usually 
Usually 
 Yes 
 No 
 Yes 
No   
 Sometimes   
 Sometimes 
Yes 
No 
Rarely 
Rarely 
   interfered with his/her activities of daily life a few years ago (or 
pre-retirement activities)? (collateral sources opinion) 
Yes 
No 
6.  Does he/she completely forget a major event (e.g., trip, party, family 
wedding) within a few weeks of the event? 
 Usually 
 Sometimes 
Rarely 
7.  Does he/she forget pertinent details of the major event? 
 Usually 
 Sometimes 
Rarely 
8.  Does he/she completely forget important information of the distant past 
(e.g., birthdate, wedding date, place of employment)? 
 Usually 
 Sometimes 
Rarely 
     9． Tell me about some recent event in his/her life that he/she should remember. (For later testing, obtain details such as 
location of the event, time of day, participants, how long the event was, when it ended and how the subject or other participants got 
there). 
Within 1 week: 
 
 
 
 
Within 1 month: 
 
 
 
 
10. When was he/she born? 
 
11. Where was he/she born? 
 
12. What was the last school he/she attended? 
     Name                      _____________________________________________________________ 
     Place                     ______________________________________________________________ 
     Grade                         _________________________________________________________ 
13. What was his/her main occupation/job (or spouse’s job if subject was not employed)? 
 
14. What was his/her last major job (or spouse’s job if subject was not employed)? 
 
15. When did he/she (or spouse) retire and why? 
 
Orientation Questions for Informant: 
 
How often does he/she know of the exact: 
 
 
1. 
Date of the Month? 
 

51 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
2. 
Month? 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
3. 
Year? 
Usually 
Sometimes 
Rarely 
Don’t Know 
4. 
Day of the Week? 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
5. 
Does he/she have difficulty with time relationships (when events happened in relation to each other)? 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
6. 
Can he/she find his/her way about familiar streets? 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
7. 
How often does he/she know how to get from one place to another outside his/her neighborhood? 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
8. 
How often can he/she find his/her way about indoors? 
 
Usually 
Sometimes 
Rarely 
Don’t Know 
 
Judgment and Problem Solving Questions for Informant: 
 
1. In general, if you had to rate his/her abilities to solve problems at the present time, would you consider them: As good as 
they have ever been 
Good, but not as good as before 
 
Fair 
 
Poor 
 
No ability at all 
 
2. Rate his/her ability to cope with small sums of money (e.g., make change, leave a small tip):  
         No loss 
Some loss 
 
Severe loss 
 
3. Rate his/her ability to handle complicated financial or business transactions (e.g., balance check-book, pay bills): 
 
No loss 
 

52 
 
Some loss 
 
Severe loss 
 
4. Can he/she handle a household emergency (e.g., plumbing leak, small fire)? 
 
As well as before 
 
Worse than before because of trouble thinking 
 
Worse than before, another reason (why) 
  
 
 
 
 
5. Can he/she understand situations or explanations? 
 
Usually 
 Sometimes 
 Rarely 
  Don’t Know 
 
6. Does he/she behave* appropriately [i.e., in his/her usual (premorbid) manner] in social situations and interactions 
with other people? 
 
Usually 
 Sometimes 
 Rarely 
  Don’t Know 
 
 
*This item rates behavior, not appearance. 
 
Community Affairs Questions for Informant:  
 
Occupational 
 
1. 
Is the subject still working? 
Yes 
No 
N/A 
If not applicable, proceed to item 4 If 
yes, proceed to item 3 
If no, proceed to item 2 
 
2. 
Did memory or thinking problems contribute to the subject’s decision 
to retire?  (Question 4 is next) 
 Yes 
 No 
 D/K 
 
3. 
Does the subject have significant difficulty in his/her job because of problems with memory 
or thinking? 
 
           Rarely or Never 
Sometimes 
Usually 
Don’t Know 
Social 
 
4. 
Did he/she ever drive a car? 
 Yes 
 No 
 
5. 
Does the subject drive a car now? 
 Yes 
 No 
 
6. 
If no, is this because of memory or thinking problems? 
 Yes 
 No 
 
7. 
If he/she is still driving, are there problems or risks because of poor thinking? 
 Yes 
 No 
 
*8.  Is he/she able to independently shop for needs? 
 
Rarely or Never 
Sometimes 
Usually 
Don’t Know 
(Needs to be accompanied 
(Shops for limited number 
on any shopping trip) 
of items; buys duplicate items 
or forgets needed items) 
 
9. Is he/she able to independently carry out activities outside the home? 
Rarely or Never 
Sometimes 
Usually 
Don’t Know 
(Generally unable 
(Limited and/or 
(Meaningful 
perform activities 
routine, e.g., 
fi i l
participation 
i

53 
 
without help) 
participation in 
h
h
activities, 
or meetings; trips to voting) 
beauty parlor) 
10. Is he/she taken to social functions outside a family home?   
 
 
 
 
 
 
Yes   
No 
If no, why not?    
 
 
11. Would a casual observer of the subject’s behavior think the subject was ill? 
 Yes 
 No 
12. If in nursing home, does he/she participate well in social functions (thinking)? 
 Yes 
 No 
 
 
 
 
*Is there enough information available to rate the subject’s level of impairment in community affairs?  Yes   
No 
If not, please probe further. 
 
Community Affairs:  Such as going to church, visiting with friends or family, political activities, professional organizations 
such as bar association, other professional groups, social clubs, service organizations, educational programs. 
 
*Please add notes if needed to clarify subject’s level of functioning in this area: 
 
 
 
Home and Hobbies Questions for Informant: 
 
1a. What changes have occurred in his/her abilities to perform household chores?     
 
 
 
1b. What can he/she still do well? 
 
 
2a. What changes have occurred in his/her abilities to perform hobbies? 
 
 
2b. What can he/she still do well? 
 
 
3. If in nursing home, what can he/she no longer do well (H and H)? 
 
 
Everyday Activities (Blessed):  
                                                            No loss            Severe loss 
4. Ability to perform household tasks 
         0       0.5         1 
Please describe:     
 
5. Is he/she able to perform household chores at the level of: (Pick 
one. Informant does not need to be asked directly). 
 
No meaningful function. 
(Performs simple activities, such as making a bed, only with much supervision) 
 
Functions in limited activities only. 
(With some supervision, washes dishes with acceptable cleanliness; sets table) 
 
Functions independently in some activities. 
(Operates appliances, such as a vacuum cleaner; prepares simple meals) 
 
Functions in usual activities but not at usual level.  

54 
 
Normal function in usual activities. 
IMPORTANT: 
Is there enough information available to rate the subject’s level of impairment in HOME & HOBBIES? 
 
If not, please probe further. 
Homemaking Tasks: Such as cooking, laundry, cleaning, grocery shopping, taking out garbage, yard work, simple care 
maintenance, and basic home repair. 
 
Hobbies:  Sewing, painting, handicrafts, reading, entertaining, photography, gardening, going to theater or symphony, 
woodworking, participation in sports. 
 
Personal Care Questions for Informant: 
 
*What is your estimate of his/her mental ability in the following areas: 
*  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A box-score of 1 can be considered if the subject’s personal care is impaired from a previous level, even if they do not receive prompting. 
 
 
 
A.Dressing(Blessed) 
Unaided 
Occasionally 
misplaced buttons, 
etc. 
Wrong 
sequence 
commonly 
forgotten 
items 
Unable todress 
0 
1 
2 
3 
 
B.Washing,grooming 
Unaided 
Needs 
Prompting 
Sometimes 
needs help 
Always or nearly 
always needs 
0 
1 
2 
3 
 
C.Eating habits 
Cleanly 
proper utensils 
Messily; 
spoon 
Simple 
solids 
Has to be fed 
completely 
0 
1 
2 
3 
 
D.Sphincter 
control 
(Blessed) 
Normal complete 
control 
Occasionally 
wets bed 
 
Frequently 
wets bed 
Doubly 
incontinent 
 
0 
1 
2 
3 

55 
 
Memory Questions for Subject: 
 
1. Do you have problems with memory or thinking? 
 Yes
 
 No 
 
2. A few moments ago your (spouse, etc.) told me a few recent experiences you had. Will you tell 
me something about those?  (Prompt for details, if needed such as location of the event, time of 
day, participants, how long the event was, when it ended and how the subject or other 
participants got there). 
 
 
Within 1 week 
1.0 – Largely correct 
 
 
 0.5 
0.0 – Largely incorrect 
 
 
Within 1 month 
1.0 – Largely correct 
 
 
 0.5 
0.0 – Largely incorrect 
 
 
 
3. I will give you a name and address to remember for a few minutes. Repeat this name and address 
after me: (Repeat until the phrase is correctly repeated or to a maximum of three trials). 
 
Elements 
1 
2 
3 
4 
5 
John 
Brown, 
42 
Market Street, 
Chicago 
John 
Brown, 
42 
Market Street, 
Chicago 
John 
Brown, 
42 
Market Street, 
Chicago 
 
(Underline elements repeated correctly in each trial). 
 
 
4. When were you born? 
 
 
 
 
5. Where were you born? 
 
 
 
 
6. What was the last school you attended? 
Name 
  
Place 
  
Grade     
 
7. What was your main occupation job (or spouse if not employed)?    
 
 
 
8. What was your last major job (or spouse if not employed)?    
 
 
 
9. When did you (or spouse) retire and why? 
 

56 
 
 
 
 
10.Repeat the name and address I asked you to remember (underline elements repeated correctly): 
 
Elements 
1 
2 
3 
4 
5 
John 
Brown, 
42 
Market Street, 
Chicago 
 
 
 
 
Orientation Questions for Subject: 
 
Record the subject’s answer verbatim for each question 
 
1. What is the date today? 
Correct
 
Incorrect 
 
 
 
 
2. What day of the week is it? 
Correct
 
Incorrect 
 
 
 
 
 
3. What is the month? 
Correct
 
Incorrect 
 
 
 
 
 
4. What is the year? 
Correct
 
Incorrect 
 
 
 
 
 
5. What is the name of this place? 
Correct
 
Incorrect 
 
 
 
 
 
6. What town or city are we in? 
Correct
 
Incorrect 
 
 
 

57 
 
 
 
7. What time is it? 
Correct
 
Incorrect 
 
 
 
 
 
8. Does the subject know who the informant is (in your judgment)? 
Correct
 
Incorrect 
 
 
Judgment and Problem Solving Questions for Subject: 
 
Instructions: If initial response by subject does not merit a grade 0, press the matter to identify the 
subject’s best understanding of the problem.  Circle nearest response. 
 
Similarities: 
 
Example:  “How are a pencil and pen alike?  (writing 
instruments) How are these things alike?” 
Subject’s Response 
1. turnip……cauliflower 
 
 
 
                    (0 = vegetables) 
                    (1 = edible foods, living things, can be  
                        cooked,etc.)            
                    (2 = answers not pertinent; differences; buy 
them) 
 
2. desk……bookcase 
                    (0 = furniture, office furniture; both hold books) 
                    (1 = wooden, legs) 
                    (2 = not pertinent, differences) 
 
Differences: 
 
       Example: “What is the difference between sugar and vinegar?  
(sweet vs sour) What is the difference between these things?” 
3. lie……mistake 
 
 
                  _______________________ 

58 
 
                   (0 = one deliberate, one unintentional) 
                   (1 = one bad the other good – or explains only one) 
                   (2 = anything else, similarities) 
 
4. river……canal 
 
 
                   _______________________ 
                   (0 = natural - artificial) 
                   (2 = anything else) 
 
Calculations: 
  
                  5.How many nickels in a dollar? 
        Correct    Incorrect 
 
                  6.How many quarters in $6.75? 
        Correct    Incorrect 
 
                 7.Subtract 3 from 20 and keep subtracting 3 from 
               each new number all the way down. 
        Correct    Incorrect 
Judgment: 
 
8. Upon arriving in a strange city, how would you locate a friend that you wished to see? 
 
                   (0 = try the telephone book, go to the courthouse for a directory; call a mutual 
friend)  
                   (1 = call the police, call operator (usually will not give address) 
  
 
 
 
(2 = no clear response) 
 
9. Subject’s assessment of disability and station in life and understanding of why 
he/she is present at the examination (may have covered, but rate here): 
 
Good Insight 
Partial Insight 
Little Insight 
 
 
 
CDR global  
Use all the information you get to make the most appropriate judgments. Evaluate the six functional areas 
respectively, fill in the scores in the corresponding "_", and note that only when the decline of ability is caused by 
cognitive impairment can the score be scored. If the severity of dysfunction is between two levels, in principle, it 
shall be evaluated as the severity level. Finally, based on the scores of six functional areas, the global CDR is 
summarized according to the following principles: 
1. 
Memory (M) is the main item, the other 5 items are the secondary items; 
2. 
When M=0.5, CDR≠0, only =0.5or 1; 
3. 
CDR=M (memory score): 

59 
 
1）When at least 3 secondary items are the same as the memory score; 
2）When only 1 or 2 minor item scores = M, no more than 2 minor item scores are on either side of M; 
3）When the scores of 3 secondary items are on one side of the memory score and the scores of the other 2 
secondary items are on the other side of the memory score; 
4）When at least 3 minor items are all 0, if M = 0.5, CDR = 0.5; 
5）Only when 1 minor item ≥ 0.5, if M = 0, CDR = 0. 
4. 
CDR≠M (memory score): 
1）When 3 or more minor item scores are greater than or less than M, CDR = most minor item scores; 
2）When M = 0.5 and at least 3 minor items score ≥ 1, CDR = 1; 
3）When M = 0, 2 or more minor items ≥ 0.5, CDR = 0.5; 
4）When M≥1, CDR≠0, at this time, if most of the other minor items = 0, CDR=0.5. 
5. Principle of near association: when the above principle is not met, CDR = M score of the closest 
secondary item (e.g., M and a secondary item score =3, 2 secondary item score =2, 2 secondary item score 
=1, CDR=2). 
CDR (sum of boxes) 
It refers to the sum of the scores of all six functional areas. 
CDR (supplementary part) 
The assessment shall be made according to the test conditions and shall not be included in the total score. 
 
 

60 
 
CLINICAL DEMENTIA RATING (CDR) 
 
 CLINICAL 
 DEMENTIA    
RATING (CDR): 
0 
0.5 
1 
2 
3 
 
Impairment 
None 0 
Questionable 0.5 
Mild 1 
Moderate 2 
Severe 
11.1 
Memory 
No memory loss or 
slight inconsistent 
forgetfulness 
Consistent slight 
forgetfulness; 
Partial recollection 
of events; 
"benign" forgetfulnes
s 
Moderate memory 
loss; more marked 
for recent events; 
defect interferes 
with everyday 
activities 
Severe memory loss;
 only highly learned 
material retained; 
new material rapidly 
lost 
Severe memory 
loss; only 
fragments 
remain 
11.2 
Orientation 
Fully oriented 
Fully oriented except
 for slight difficulty 
with time relationshi
ps 
Moderate difficult
y with time relati
onships; oriented 
for place at exam
ination; may have
 geographic disori
entation elsewhere 
Severe difficulty 
with time relation
ships; usually diso
riented to time, of
ten to place 
Oriented to perso
n only 
11.3 
Judgment &Pr
oblem Solving 
Solves everyday pro
blems 
& handles busines
s & financial affai
rs well; 
judgment good in re
lation 
to past performance 
Slight impairment in 
solving problems, si
milarities, and differ
ences 
Moderate diff
iculty in han
dling proble
ms, similariti
es, and differ
ences; social 
judgment usu
ally maintain
ed 
Severely impaired 
in handling proble
ms, similarities, an
d differences; socia
l judgment usually 
impaired 
Unable to mak
e judgments or
solve problems 
11.4 
Community Af
fairs 
Independent function
at usual level in job,
 shopping, volunteer 
and social groups 
Slight impairment 
in these activities 
Unable to functio
n independently at
 these activities al
though may still 
be engaged in so
me; appears norm
al to casual inspe
ction 
No pretense of independent function outs
ide home 
Appears well enough
 to be taken to func
tions outside a famil
y home 
Appears too ill t
o be taken to fu
nctions outside a
 family home 

61 
 
11.5 
Home and Ho
bbies 
Life at home, hobbie
s, and intellectual int
erests well maintaine
d 
Life at home, hobbi
es, and intellectual i
nterests slightly impa
ired 
Mild but definite 
impairment of fun
ction at home; m
ore difficult chore
s abandoned; mor
e complicated ho
bbies and interest
s abandoned 
Only simple chore
s preserved; very 
restricted interests,
 poorly maintaine
d 
No significant fu
nction in home 
11.6 
Personal Care 
Fully capable of self-care 
Needs prompting 
Requires assistance i
n dressing, hygiene, 
keeping of personal 
effects 
Requires much
 help with per
sonal care; fre
quent incontine
nce 
 
 
 
 

62 
 
Appendix12: Participating unit and participant number 
A total of 8 digits: the number of each unit (3) + the number of the participant (5), with a horizontal bar in the 
middle. For example, the number of eighth participant in Xuanwu Hospital is 001-00008. The number of each 
participating unit is shown in the table below. 
NO. 
Unit name 
NO. 
Unit name 
001  
Xuanwu Hospital, Capital Medical University 
035 
Jiangxi Provincial People's Hospital 
002  
Beijing Tian Tan Hospital, Capital Medical 
University 
036  
Anshanshi Changda the Hospital 
003  
Beijing Chao-Yang Hospital, Capital Medical 
University 
037  
Affiliated Zhongshan Hospital of Dalian 
University 
004  
Fu Xing Hospital, Capital Medical University 
038  
The First Hospital of China medical 
University 
005  
Peking Union Medical College Hospital 
039  
Baotou Central Hospital  
006  
Peking University First Hospital 
040  
General Hospital of Ningxia Medical 
University  
007  
Peking University Third Hospital 
041  
People’s Hospital of Ningxia Hui 
Autonomous Region 
008  
Chinese PLA General Hospital 
042  
The Affiliated Hospital of Qingdao 
University 
009  
China-Japan Friendship Hospital 
043  
78th Hospital of the People's Liberation 
Army 
010  
Beijing Geriatric Hospital 
044  
Qilu Hospital of Shandong University 
011 
Dalian Municipal Hospital Affiliated of Dalian 
Medical University 
045  
Qilu Hospital of Shandong University 
(Qingdao) 
012  
Fujian Medical University Union Hospital 
046  
Shangdong Provincial Hospital 
013  
Guangzhou Brain Hospital 
047  
QingDao Municipal Hospital 
014  
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
University 
048  
First Hospital of Shanxi Medical 
University 
015  
The first Affiliated Hospital of Guangxi Medical 
University 
049  
Tangdu Hospital, Fourth Military 
Medical University 
016  
The Affiliated Hospital of Guizhou Medical 
University 
050  
The first Affiliated Hospital of Xi’ an 
Jiao Tong University 

63 
 
017 
HanDan Central Hospital 
051  
Rui Jin Hospital Shanghai Jiao Tong 
University School of Medicine 
018 
Heibei General Hospital 
052 
Renji Hospital Shanghai Jiao Tong 
University School of Medicine 
019 
Shijiazhuang First Hospital 
053 
Shanghai Changzheng Hospital 
020 
Tangshan Workers Hospital 
054 
Affiliated Hospital of North Sichuan 
Medical University 
021 
Hennan Provincial People’s Hospital 
055 
Tianjin Huanhu Hospital 
022 
KaiFeng Central Hospital 
056 
General Hospita of Tianjin Medical 
University 
023 
People's Hospital of Zhengzhou 
057 
Xinjiang Autonomous Region Chinese 
Medicine Hospital 
024 
The First Affiliated Hospital of Harbin Medical 
University 
058 
Ningbo City Medical Treatment Center 
Lihuili Hospital 
025 
Tongji Hospital, Huazhong University of Science 
and Technology 
059 
The First Affiliated Hospital of 
Wenzhou Medical University 
026 
People's Hospital Affiliated Hubei University of 
Medicine 
060 
The First Affiliated Hospital, Zhejiang 
University 
027 
Zhongnan Hospital of Wuhan University 
061 
Shao Yifu Hospital, Zhejiang University 
of Medicine 
028 
The Third Xiangya Hospital of Central South 
University 
062 
Zhejiang Provincial People's Hospital 
029 
Xiangya Hospital, Central South University 
063 
Daping Hospital of the Third Military 
Medical University 
030 
The First Hospital of Jilin University 
064 
The Second Affiliated Hospital of 
Chongqing Medical University 
031 
China-Japan Friendship Hospital of Jilin 
University 
065 
The First Hospital Affiliated Anhui 
Medical University 
032 
Subei People's Hospital 
066 
Chongqing General Hospital 
033 
Affiliated Hospital of Nantong University 
067 
Dongfang Hospital, Beijing University 
of Chinese Medicine 

64 
 
034 
Xuzhou Mine General Hospital 
068 
Zigong First People's Hospital