China Cognition and Aging Study

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 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. 10. To investigate the level of stigma and discrimination and its influencing factors in patients with Alzheimer's disease and their caregivers.

This study involved participants including Mild cognitive impairment (MCI) and its subtypes、Sporadic Alzheimer's disease (SAD)、 Familial Alzheimer's disease (FAD)、Vascular dementia (VaD)、Normal control in community population and hospital population. Research contents are as follow: 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 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.