China Cognition and Aging Study

Community population: age ≥ 55 years, male or female, with consent to participant thestudy. 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 areconsistent 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, multiplesclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
3. Other systemic diseases that can cause cognitive impairment (such as liver, renal andthyroid 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 andStatistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-R). Thediagnosis of AD is made using the National Institute of Neurologic and CommunicativeDisorders 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:
4. With a family history of dementia.
5. Other neurological diseases that can cause brain dysfunction (such as depression,brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiplesclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
6. Other systemic diseases that can cause cognitive impairment (such as liver, renal andthyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis,HIV infection, alcohol and drug abuse, etc.).
7. Mental and neurodevelopmental retardation.
8. Contraindications to MRI.
9. Suffering from a disease that cannot be combined with cognitive examination.
10. Refuse to draw blood.
11. 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 anystudy-related procedures.
2. Members in FAD pedigree (FAD is defined as at least two first- degree relatives sufferfrom 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 diagnosisof AD is made using NINCDS-ADRDA or NIA-AA criteria. A diagnosis of MCI is assignedaccording to Petersen criteria. Exclusion criteria:
5. 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 andother types of dementias such as vascular dementia (VaD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD).
6. MRI and laboratory tests do not support or rule out a diagnosis of AD.
7. Severe circulatory, respiratory, urinary, digestive, hematopoietic diseases (such asunstable angina, uncontrollable asthma, active gastric bleeding) and cancer.
8. Participant has severe psychiatric illness or severe dementia that would interfere incompleting initial and follow-up clinical assessments.
9. With history of alcohol or drug abuse.
10. Pregnant or lactating women.
11. No reliable insiders.
12. 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 anassessment of hippocampal volume.

1. multiple (≥3) supratentorial subcortical small infarcts (3-20 mm in diameter) with orwithout any degree of white matter lesion (WML); or moderate to severe WML (Fazekasscore ≥ 2), with or without small infarction; or ≥ 1 subcortical small infarct in keyregions, such as caudate nucleus, globus pallidus, or thalamus.
2. no cortical and watershed infarction, hemorrhage, hydrocephalus, or WML with specificcauses (such as multiple sclerosis).
3. no hippocampus or entorhinal cortex atrophy (MTA score = 0 point). Exclusion criteria:
4. Other neurological diseases that can cause brain dysfunction (such as depression,brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiplesclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
5. Other systemic diseases that can cause cognitive impairment (such as liverinsufficiency, renal insufficiency, thyroid insufficiency, severe anemia, folic acidor vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.).
6. With a history of mental illness or those with congenital mental retardation.
7. Suffering from a disease that cannot be combined with a cognitive examination.
8. Contraindications to MRI.
9. Refuse to draw blood.
10. 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 thoseeducated less than 7 years, >27 points for those educated equal to or more than 7years. 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:
3. Subjects with abnormal MMSE or MoCA scores.
4. Subjects with a history of cerebral infarction, traumatic brain injury or relatedmanifestations in MRI.
5. Other neurological diseases that can cause brain dysfunction (such as depression,brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiplesclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
6. Other systemic diseases that can cause cognitive impairment (such as liver, renal andthyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis,HIV infection, alcohol and drug abuse, etc.).
7. Mental and neurodevelopmental retardation.
8. Suffering from a disease that cannot be combined with a cognitive examination.
9. Contraindications to MRI.
10. Refuse to draw blood.
11. Refuse to sign the informed consent at baseline.