Study on Biomarkers for Early Diagnosis of Alzheimer's Disease

Study Overview
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Brief Summary
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The project of Bio-AD is a population- based cohort study among the elderly in China. The project includes not only Alzheimer's disease (AD including familial AD and sporadic AD), but also other clinical stage of AD, as well as elderly people with normal cognitive function. The project will collect, detect and screen the special biomarkers at different clinical stage of AD based on body fluid, gene and brain image. The standard and consistent assessment protocols are employed to obtain clinical, cognitive, genetic, neuroimaging and biospecimen data. The purpose of this project is to establish a panel of biomarkers which could be used to diagnose AD at the early stage, and to establish a risk prediction models for AD to predict the 5-years risk of the onset and progression of AD among elderly population in China.

Detailed Description
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Set up a large population- based cohort including AD, MCI, pre-MCI, other neurodegenerative diseases, and elderly individuals with normal cognitive function. Collect the information of clinical and neuropsychological assessment, individual traits and social environmental factors, and neuroimaging data, as well as the biological samples, such as peripheral blood and cerebrospinal fluid. Screen biomarkers with high specificity and sensitivity from peripheral blood, cerebrospinal fluid and neuroimaging to distinguish different clinical stages of AD at baseline. Screen the AD-associated gene and their risk variants. Establish a panel of AD-specific biomarkers for the preliminary development of diagnostic kit. Identify AD-relevant factors and the special biomarkers to create a preliminary risk models to predict the onset and progression of AD. Follow up the cohort for next 5 years and collect the multiple information and biological samples each year to validate and revise the risk prediction models and the diagnostic kit of AD.

Official Title
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Study on Body Fluid, Gene and Neuroimaging Biomarkers for Early Diagnosis of Alzheimer's Disease

Conditions
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Alzheimer Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from participant or legal guardian prior to any study-related procedures. Aged 18 (inclusive) or older. 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. A diagnosis of pre-MCI group is assigned by β-Amyloid positive or APOE ε4 carrier or complains of cognitive impairment, but not up to MCI or cognitive impairment. Normal cognitive function assessed/evaluated by MMSE, CDR and other cognitive function scales. Follow up 5 years and collect the information. Exclusion Criteria: Under age 18. Medical or psychiatric illness that would interfere in completing initial and follow-up visits. No one can serve as a study informant. With current or past neurological or psychiatric illnesses such as schizophrenia, epilepsy, brain tumors, severe head trauma and other diseases which can induce dementia. Refused to complete a cognitive test and provide biospecimen. With history of alcohol or drug abuse.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AD group<br>Dementia is diagnosed according to the 2011 NIA-AA criteria. | |
| MCI group<br>aMCI diagnosed according to the criteria of 2004 Peterson. | |
| pre-MCI group<br>β-Amyloid positive or APOE ε4 carrier or complains of cognitive impairment; not up to MCI or cognitive impairment. | |
| Other neurodegenerative diseases<br>Frontotemporal Dementia; or Parkinson's disease | |
| Cognitive normal group<br>Individuals are with normal cognitive function and ≥ 60 years old. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A multiple diagnostic kit for early diagnosis of AD. | A panel of special biomarkers is identified for early diagnosis of AD. | An Average of 1 year | 
| A 5-years risk prediction model for onset and progression of AD among elderly population in China. | A 5-years risk prediction model including multiple factors to predict the onset and progression of AD in China. | An Average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A panel of biomarker with high specificity and sensibility | Screening the biomarker with high specificity and sensibility in body fluid at different clinical stage of AD. | An Average of 1 year | 
| AD-associated genes in Chinese. | AD-associated genes and their risk variants will be identified by whole exome sequencing in this project. | An Average of 1 year | 
| Neuroimaging biomarkers for AD | The certain threshold on neuroimaging biomarkers will be established to distinguish the different clinical stage of AD. | An Average of 1 year | 
| Risks and protective factors for AD among elderly in China | The risks and protective factors of individual and environment will be estimated in this project. | An Average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease