This is a multi-center study that has three cohorts: 1) cognitive normal cohort (CN), 2) Alzheimer's disease cohort (AD) and 3) vascular cognitive impairment cohort (VCI). The goal of this study is to understand the risk factors of AD and VCI and to identify high risk patients for early intervention. It will collect demographic information, family history, medical history, neuropsychological tests, imaging studies and biological samples through standard and uniform procedures.

In this prospective study, we will recruit subjects into one of the three groups based on inclusion and exclusion criteria: 1) CN, 2) AD and 3) VCI. We will follow up with each of them subject at designated time points up to 2 years. We will collect demographic, medical, imaging (MRI and PET scans), genetic information and various biological samples (blood, saliva, urine and feces) during the study period. This study uses a case-control study design. The matched cases will have similar age, gender and education levels. By studying the relationship between risk factors of AD and VCI, we will establish norms and parameters in the Chinese population.

1. The inclusion and exclusion criteria of AD group.

   1.1 The AD group inclusion criteria: 1.1.1 Aged 40-100 years old (≥ 40 years old, ≤ 100 years old). 1.1.2 Diagnosed with AD according to Alzheimer disease diagnostic criteria following NINCDS-ADRDA1984 or NIA-AA 2011 guideline.

   1.1.3 Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments.

   1.1.4 Had at least 3 years of education. 1.1.5 Signed informed consent.

   1.2 The AD group exclusion criteria: 1.2.1 Sequelae after previous history of severe central nervous system infection, multiple sclerosis, autoimmune encephalitis, Hashimoto's encephalopathy, etc.

   1.2.2 Previous history of instable epilepsy. 1.2.3 Systemic diseases affect the central nervous system (CNS), such as abnormal liver and kidney functions.

   1.2.4 History of hereditary diseases that affect cognitive function (such as Huntington's disease, Down's syndrome, CADASIL, adrenal leukodystrophy, mitochondrial encephalopathy, etc.).

   1.2.5 Infection and immune-related diseases affecting the central nervous system (systemic lupus erythematosus, undertreated HIV infection or a history of CNS syphilis infection, etc.).

   1.2.6 Metabolic and endocrine disorders (requiring new treatment or adjustment of current treatment for thyroid dysfunction, folate or vitamin B12 deficiency).

   1.2.7 Had contraindications for MRI (e.g., pacemakers, stents, claustrophobia.) or did not cooperate with PET scans.

2. The inclusion and exclusion criteria of post-stroke cognitive observation group.

   2.1 The inclusion criteria of post-stroke cognitive observation group: 2.1.1 Aged 40-100-years old (≥ 40 years old, ≤ 100 years old). 2.1.2 Cerebral infarction is diagnosed according to World Health Organization diagnostic criteria13 and was the first symptomatic onset.

   2.1.3 The time from onset to enrollment was less than 7 days. 2.1.4 Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments.

   2.1.5 Had at least 3 years of education. 2.1.6 Signed informed consent.

   2.2 The exclusion criteria of post-stroke cognitive observation group: 2.2.1 Prior to the onset of acute infarction had no conditions known to affect cognitive function, such as vascular dementia, dementia with Lewy body dementia, frontotemporal dementia, Parkinson's disease dementia, epilepsy, stroke, hydrocephalus, multiple sclerosis, traumatic brain injuries, genetic disorders affecting cognition, alcoholism, uncontrolled depression or other psychiatric disorders and Alzheimer's disease and IQCODE>3.5.

   2.2.2 Sequelae after previous history of severe central nervous system infection, multiple sclerosis, autoimmune encephalitis, Hashimoto's encephalopathy, etc.

   2.2.3 Previous history of instable epilepsy. 2.2.4 Systemic diseases affect the CNS, for abnormal liver and kidney functions.

   2.2.5 History of hereditary diseases that affect cognitive function (such as Huntington's disease, down syndrome, CADASIL, adrenal leukodystrophy, mitochondrial encephalopathy, etc.).

   2.2.6 Infection and immune-related diseases affecting the central nervous system (systemic lupus erythematosus, undertreated HIV infection or a history of CNS syphilis infection, etc.).

   2.2.7 Metabolic and endocrine disorders (requiring new treatment or adjustment of current treatment for thyroid dysfunction, folate or vitamin B12 deficiency).

   2.2.8 Reject or had contraindications for MRI (e.g., pacemakers, stents, claustrophobia.).

3. The inclusion and exclusion criteria of normal cognitive group.

3.1 The inclusion criteria of normal cognitive group: 3.1.1 Aged 40-100 years old (≥ 40 years old, ≤ 100 years old). 3.1.2 The patients are cognitively normal and able to live and work independently.

3.1.3 Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments.

3.1.4 Had at least 3 years of education. 3.1.5 Signed informed consent.

3.2 The exclusion criteria of normal cognitive group: 3.2.1 The patients had no conditions known to affect cognitive function, such as vascular dementia, dementia with Lewy body dementia, frontotemporal dementia, Parkinson's disease, epilepsy, stroke, hydrocephalus, multiple sclerosis, traumatic brain injuries, genetic disorders affecting cognition, alcoholism, uncontrolled depression or other psychiatric disorders, Parkinson's disease, epilepsy or Alzheimer's disease.

3.2.2 Sequelae after previous history of severe central nervous system infection, multiple sclerosis, autoimmune encephalitis, Hashimoto's encephalopathy, etc.

3.2.3 Previous history of instable epilepsy. 3.2.4 Systemic diseases affect the CNS, for abnormal liver and kidney functions.

3.2.5 History of hereditary diseases that affect cognitive function (such as Huntington's disease, down syndrome, CADASIL, adrenal leukodystrophy, mitochondrial encephalopathy, etc.).

3.2.6 Infection and immune-related diseases affecting the central nervous system (systemic lupus erythematosus, undertreated HIV infection or a history of CNS syphilis infection, etc.).

3.2.7 Metabolic and endocrine disorders (requiring new treatment or adjustment of current treatment for thyroid dysfunction, folate or vitamin B12 deficiency).

3.2.8 Reject or had contraindications for MRI (e.g., pacemakers, stents, claustrophobia.).

Alzheimer's disease cohort and post-stroke cognitive observation cohort will be recruited from participating hospitals.

Cognitively normal cohort will be recruited from the community.

All data are available upon reasonable request.

Data will be available at one year after the study completion.

Committee review