China Cognition and Aging Study

Amnestic mild cognitive impairment (aMCI)

Inclusion Criteria:

1. Diagnosis according to 2004 Peterson's aMCI criteria.

2. Clinical Dementia Rating (CDR) = 0.5.

3. Memory loss is prominent, and may also be with other cognitive domain impairment.

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 vascular 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. Other diseases known to cause cognitive impairment.

6. Contraindications to nuclear magnetics.

7. Suffering from a disease that cannot be combined with cognitive examination.

8. Refuse to draw blood.

9. Refuse to sign the informed consent at baseline

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 Assocation (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. Other diseases known to cause cognitive impairment.

6. Contraindications to nuclear magnetics.

7. Suffering from a disease that cannot be combined with cognitive examination.

8. Refuse to draw blood.

9. Refuse to sign the informed consent at baseline

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 who carry mutations or not carry mutations in familial Alzheimer's disease pedigree (familial Alzheimer disease is defined as at least two first- degree relatives).

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 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 Assocation (NIA-AA) criteria. A diagnosis of mild cognitive impairment (MCI) is assigned according to Petersen criteria.

Exclusion Criteria:

1. Under age 18.

2. Medical or psychiatric illness that would interfere in completing initial and follow-up visits.

3. No one who can serve as a study informant.

4. With current or past neurological or psychiatric illnesses such as schizophrenia, epilepsy, brain tumors, severe head trauma and other diseases which can induce dementia.

5. With history of alcohol or drug abuse.

Vascular cognitive impairment (VCI)

Inclusion Criteria:

1. Diagnosis according to the criteria for small vessel VCI, with the following three core elements:

1. Cognitive impairment: memory decline can be highlighted

2. Vascular factors

3. Causal relationship between cognitive impairment and vascular factors

2. Cognitive impairment lasts for 3 months or more, and the CDR global score ≥0.5 point.

3. All patients need to meet the following MRI criteria:

1. Multiple (≥3) small infarcts (3-20 mm in diameter) with or without any degree of white matter lesions (WML); or moderate to severe WML (Fazekas score ≥ 2) , with or without small infarction; or ≥ 1 small infarct in key parts of the cortex, such as: caudate nucleus, globus pallidus, thalamus and so on.

2. No WML caused by cortical infarction, watershed infarction, hemorrhage, hydrocephalus, or other causes (such as multiple sclerosis).

3. No hippocampus or entorhinal cortex atrophy, Medial Temporal Lobe Atrophy (MTA)≤ 1 point.

4. Subjects and their informed persons can complete relevant and follow-up examinations.

5. Subjects or their authorized legal guardians sign the informed consent.

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, renal, and thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.）.

3. Other diseases known to cause cognitive impairment.

4. Hereditary or inflammatory small vessel disease, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

5. Contraindications to nuclear magnetics.

6. Refuse to draw blood.

7. Refuse to sign the informed consent at baseline.

APOE gene cohort

Inclusion Criteria:

1. Aged 18 (inclusive) or older.

2. APOE genotyping has to be obtained from all subjects.

3. 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 confirmed by MRI imaging.

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. Other diseases known to cause cognitive impairment.

7. Contraindications to nuclear magnetics.

8. Refuse to draw blood.

9. Refuse to sign the informed consent at baseline.