China Longitudinal Aging and Cognitive Impairment Study

Inclusion Criteria: Inclusion Criteria:

1. Cognitive normal aging (CN) 1. 40 years and older , without cognitive impairment,MMSE≥22 2. Informed consent is signed by the participant
2. Subjective cognitive impairment (SCI) Participants aged 40 and older, with absence ofdementia (by DSM IV and DSM V) criteria. Normal age-, sex-, and education-adjustedperformance on standardized cognitive tests, which are used to classify mild cognitiveimpairment (MCI) or prodromal AD. Self-experienced persistent decline in cognitivecapacity in comparison with a previously normal status and unrelated to an acuteevent. Answering "yes" to both of the following questions: "Do you feel like yourmemory or thinking is becoming worse?" and "Does this concern you?"
3. Mild cognitive impairment (MCI) 1. 40 years and older 2. Diagnosis according to 2004Peterson's MCI criteria. 3. Clinical Dementia Rating (CDR) = 0.5. 4. Memory loss isprominent, and may also be with other cognitive domain impairment.
4. Insidious onset, slow progress.
5. Alzheimer's disease (AD)
6. 50 years and older
7. Dementia is diagnosed according to the criteria described by the Diagnostic andStatistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-R).The diagnosis of AD according to the National Institute of Neurologic andCommunicative Disorders and Stroke and the Alzheimer's Disease and RelatedDisorders Association (NINCDS- ADRDA) or National Institute on Aging and theAlzheimer's Assocation (NIA-AA) criteria.
8. Subjects and their informed persons can complete relevant and follow-upexaminations.
9. Subjects or their authorized legal guardians sign the informed consent. Vascularcognitive impairment (VCI)
10. 40 years and older 2. 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 3.Cognitiveimpairment lasts for 3 months or more, and the CDR global score ≥0.5 point.

4. All patients need to meet the following MRI criteria:
5. Multiple (≥3) small infarcts (3-20 mm in diameter) with or without any degree ofwhite matter lesions (WML); or moderate to severe WML (Fazekas score ≥ 2) , withor without small infarction; or ≥ 1 small infarct in key parts of the cortex,such as: caudate nucleus, globus pallidus, thalamus et al.
6. No WML caused by cortical infarction, watershed infarction, hemorrhage,hydrocephalus, or other causes (such as multiple sclerosis).
7. No hippocampus or entorhinal cortex atrophy, Medial Temporal Lobe Atrophy (MTA)≤ 1 point.
8. Subjects and their informed persons can complete relevant and follow-upexaminations.
9. Subjects or their authorized legal guardians sign the informed consent.

Exclusion Criteria: Cognitive normal aging (CN)

1. any disease that can cause cognitive impairment (such as Alzheimer's disease,dementia with Lewy bodies (DLB), frontotemporal dementia (FTLD), Parkinson'sdisease dementia (PDD), intracranial masses that impair cognition, history ofsevere brain trauma, normal pressure hydrocephalus, cerebrovascular disease withobvious clinical symptoms, etc.
2. sequelae after previous history of severe central nervous system infection,multiple sclerosis, autoimmune encephalitis, Hashimoto's encephalopathy, etc.
3. previous history of instable epilepsy
4. systemic diseases affect the central nervous system, for abnormal liver andkidney functions (abdominal dialysis, hemodialysis, AST≥3× upper limit of normalvalue (ULN), ALT≥3× upper limit of normal value (ULN) or total bilirubin ≥2×ULN
5. history of hereditary diseases that affect cognitive function (such asHuntington's disease, down syndrome, CADASIL, adrenal leukodystrophy,mitochondrial encephalopathy, etc.)
6. long-term heavy drinking history (alcohol content more than 42 degree liquor,more than 150g/day, alcohol consumption more than 12 months)
7. history of severe pulmonary diseases (COPD, pulmonary encephalopathy)
8. history of serious cardiovascular disease (heart failure, severe hypertension)
9. infection and immune-related diseases affecting the central nervous system (systemic lupus erythematosus, undertreated HIV infection or a history of CNSsyphilis infection, etc.)
10. metabolic and endocrine disorders (requiring new treatment or adjustment ofcurrent treatment for thyroid dysfunction, folate or vitamin B12 deficiency)
11. unstable psychosis or long-term use of antipsychotic drugs (more than 6 months)
12. history of malignant tumors (tumors of nervous system and other sites) active fornearly 1 year
13. contraindications for MRI (e.g. pacemakers, stents, claustrophobia, etc.) or donot cooperate or cannot carry out PET examination
14. uneducated illiterates
15. hearing impairment, visual impairment and poor coordination
16. withdraw or reject the study Subjective cognitive impairment (SCI) and Mildcognitive impairment (MCI)
17. With history of stroke and a neurological focal sign, the imaging findings areconsistent with cerebral vascular disease (Fazekas score ≥ 2 points).
18. 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 pressurehydrocephalus, etc.).
19. Other systemic diseases that can cause cognitive impairment（such as liver, renaland thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency,syphilis, HIV infection, alcohol and drug abuse, etc.）.
20. Mental and neurodevelopmental retardation.
21. Other diseases known to cause cognitive impairment.
22. Contraindications to nuclear magnetics.
23. Suffering from a disease that cannot be combined with cognitive examination.
24. Refuse to draw blood.
25. Refuse to sign the informed consent at baseline Alzheimer's disease (AD)
26. 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 pressurehydrocephalus, etc.).
27. Other systemic diseases that can cause cognitive impairment（such as liver, renaland thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency,syphilis, HIV infection, alcohol and drug abuse, etc.）.
28. Mental and neurodevelopmental retardation.
29. Other diseases known to cause cognitive impairment.
30. Contraindications to nuclear magnetics.
31. Suffering from a disease that cannot be combined with cognitive examination.
32. Refuse to draw blood.
33. Refuse to sign the informed consent at baseline Vascular cognitive impairment (VCI)
34. 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 pressurehydrocephalus, etc.).
35. 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.）.
36. Other diseases known to cause cognitive impairment.
37. Hereditary or inflammatory small vessel disease, such as cerebral autosomaldominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
38. Contraindications to nuclear magnetics.
39. Refuse to draw blood.
40. Refuse to sign the informed consent at baseline