China Alzheimer's and Neurodegenerative Disorder Research

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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China National Clinical Research Center Alzheimer's Disease and Neurodegenerative Disorder Research

Conditions
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Cognitive Impairment

Participation Criteria
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Eligibility Criteria
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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. 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.). 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.).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Alzheimer's disease cohort<br>Aged 40-100 years old (≥ 40 years old, ≤ 100 years old). Diagnosed with AD according to Alzheimer disease diagnostic criteria following NINCDS-ADRDA 1984 or NIA-AA 2011 guideline. Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments. Had at least 3 years of education. Signed informed consent. | |
| Post-stroke cognitive observation cohort<br>Aged 40-100-years old (≥ 40 years old, ≤ 100 years old). Cerebral infarction is diagnosed according to World Health Organization diagnostic criteria and was the first symptomatic onset. The time from onset to enrollment was less than 7 days. Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments. Had at least 3 years of education. Signed informed consent. | |
| A cohort of people with normal cognitive function<br>Aged 40-100 years old (≥ 40 years old, ≤ 100 years old). The patients are cognitively normal and able to live and work independently Had adequate hearing, vision and comprehension and verbal expression to complete the cognitive assessments. Had at least 3 years of education. Signed informed consent. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Data records | We will record the number of participants at several follow-up visits, the basic condition at the follow-up. If the visit is not completed, record the cause of this loss. At baseline, record the demographic information, past medical history and medication history, vital signs and neuropsychological scales. The PET-CT scan were recorded during the 4-year visit. Collect the results of cerebral MRI, laboratory tests and neuropsychological scales of all participants at baseline, 12, 24, 36 and 48 months and biological samples. For VCI cohort, we will record the basic conditions and partial neuropsychological scales at 3-month and 6-month follow-up. | 4-5 years | 
| Neuropsychological scales | Mini-Mental State Examination (MMSE), Montreal-Cognitive Assessment (MoCA), the Geriatric Depression Scale (GDS), The Activities of Daily Living Questionnaire(ADL), Digit Span Memory Test, Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test(ROCF), Trail Making Test A and B, Stroop test, Verbal Fluency Test, Boston Naming Test, Clock-Drawing Test, Narcissism Test (NPI), Symbol Digit Modalities Test(SDMT), Clinical Dementia Rating (CDR) | 4-5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, vascular cognitive impairment, dementia