China Cognition and Aging Study

Summary

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.

Eligibility

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.

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 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.

1. 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.
2. no cortical and watershed infarction, hemorrhage, hydrocephalus, or WML with specific causes (such as multiple sclerosis).
3. 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.).
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.

Conditions7

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