Early Cognitive Impairment as a function of Alzheimer's Disease and Trauma

阿尔茨海默病和创伤导致的早期认知障碍

• 批准号: 10479319
• 负责人: MARK W LOGUE
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10479319
• 关键词: Address; African; African American; African ancestry; Age; Age-associated memory impairment; Aging; Algorithms; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Area; Benchmarking; Blood Vessels; Clinical; Cognitive; Cohort Studies; Complex; Computerized Medical Record; Craniocerebral Trauma; Data; Dementia; Development; Diabetes Mellitus; Diagnosis; Disparity; Early Diagnosis; Environment; Environmental Exposure; Environmental Risk Factor; Genes; Genetic; Genetic Diseases; Genetic Risk; Genome; Genomics; Genotype; Health; Hispanic; Hispanic Populations; Hispanic ancestry; Impaired cognition; Individual; International Classification of Disease Codes; Knowledge; Late Onset Alzheimer Disease; Link; Machine Learning; Medical Records; Methods; Military Personnel; Not Hispanic or Latino; Participant; Pathology; Patient Self-Report; Patients; Performance; Phenotype; Population; Post-Traumatic Stress Disorders; Prevalence; Proxy; Psychopathology; Reporting; Research Priority; Risk; Risk Factors; Sensitivity and Specificity; Source; Techniques; Toxin; Trauma; Traumatic Brain Injury; Variant; Vascular Dementia; Veterans; Work; agent orange; biobank; cognitive testing; cohort; combat; combat trauma; dementia risk; disorder risk; effective therapy; follow-up; gene environment interaction; genetic analysis; genetic architecture; genetic association; genetic risk factor; genetic variant; genome wide association study; genome-wide; health disparity; improved; machine learning method; mild cognitive impairment; phenotyping algorithm; polygenic risk score; programs; risk prediction; risk variant; symptomatology

Risk for dementia, including late-onset Alzheimer’s disease (AD) and vascular dementia, is determined by a complex mix of environmental, health, and genetic factors. Veterans have higher rates of vascular problems, PTSD, combat trauma, and traumatic brain injuries, which have all been linked to increased rates of age-related cognitive impairment and dementia. Further, studies have indicated that these Veteran-relevant exposures may interact with AD genetics to further increase the risk of cognitive decline. This application represents an outgrowth of a project examining dementia and combat related gene by environment (GxE) interactions in the Million Veteran Program (MVP), one of the world’s largest electronic-medical record (EMR) linked biobanks. The original 2-year MVP Gamma project (MVP015) generated working definitions of mild cognitive impairment (MCI), AD, and all-cause dementia from the VA EMR. These were examined for association with combat exposure, head injury, and PTSD in aging Veterans. We found evidence that head injury, combat, PTSD symptomatology, and AD genetic risk variants were all associated with self-reported cognitive difficulties and MCI in Veterans as young as 45-55, and with AD and related dementias in those age 65+. We additionally identified GxE interactions between candidate variants in several genes and combat/head injury on MCI and AD risk. In this application, we propose expanding on the initial study, by 1) performing a genome wide association study (GWAS) of Dementia cases and controls in multiple ancestry groups as well as examining the performance of GWAS-based genetic risk scores in African American and Hispanic MVP participants, 2) performing multivariate GxE analyses examining a range of Veteran relevant health exposures, 3) Further developing and validating dementia diagnoses in MVP for genetic analyses including a machine learning based method of identification of Dementia cases. This project will expand on our continuing work and increase our knowledge of the impact of Veteran specific environmental exposures and their interactions with AD genes on risk for AD and dementia.

痴呆症的风险，包括晚发性阿尔茨海默病（AD）和血管性痴呆