Leveraging Existing Aging Research Networks to investigate TBI and AD/ADRD risk (LEARN TBI & AD)

利用现有的老龄化研究网络来调查 TBI 和 AD/ADRD 风险（了解 TBI

• 批准号: 10533343
• 负责人: Kristen Dams-O'Connor
• 金额: $ 104.54万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10533343
• 关键词: Abate; Activities of Daily Living; Address; Adult; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Autopsy; Blood Vessels; Brain; Chronic Disease; Clinical; Clinical Data; Cognition; Cohort Studies; Communities; Complex; Consensus; Craniocerebral Trauma; Data; Data Set; Dementia; Dementia with Lewy Bodies; Diagnosis; Disease; Elderly; Environmental Risk Factor; Epidemiology; Evaluation; Framingham Heart Study; Frequencies; Funding; Genetic; Genetic Risk; Genotype; Incidence; Individual; Intervention; Investigation; Lewy Bodies; Longitudinal Studies; Longitudinal cohort study; Measurement; Measures; Memory; Meta-Analysis; Metadata; Methodology; Methods; Minority; Modeling; Modernization; Modification; Moods; Morbidity - disease rate; Motor; Nerve Degeneration; Neurodegenerative Disorders; Neurofibrillary Tangles; Outcome; Parkinson Disease; Participant; Pathologic; Pathology; Persons; Planet Mars; Prevention strategy; Process; Psychometrics; Reporting; Research; Risk; Risk Factors; Role; Sample Size; Sampling; Scanning; Scientific Advances and Accomplishments; Senile Plaques; Slide; Subgroup; Testing; Traumatic Brain Injury; United States National Institutes of Health; Work; alpha synuclein; analytical method; chronic traumatic encephalopathy; clinical diagnosis; cohort; comorbidity; contact sports; data resource; dementia risk; diagnostic criteria; digital; endophenotype; epidemiology study; genetic risk factor; genomic locus; head impact; improved; indexing; individual patient; lifestyle factors; longitudinal design; military service; neuropathology; phenotypic data; prospective; protective factors; protein TDP-43; religious order study; research study; response; risk variant; secondary analysis; tau Proteins; therapy development

Project Summary/Abstract This R01 proposal, “Leveraging Existing Aging Research Networks to investigate Traumatic Brain Injury (TBI) and Alzheimer’s Disease (AD) and AD related dementia (ADRD) risk” (LEARN TBI & AD), is in response to PAR 17-088 which requests secondary analyses of existing data resources to address clinical aging research questions. In this interdisciplinary project, we will use existing and newly collected data from 5 of the largest NIH-funded studies of aging (Adult Change in Thought Study, Religious Orders Study, Memory and Aging Project, Minority Aging Research Study, and Framingham Heart Study), to examine the association of TBI and repetitive head impacts (RHI) with AD/ADRD. Decades of research on the relationship between head trauma and dementia remain inconclusive; studies have reported contradictory findings but differences in methods and measurements preclude direct comparisons. Individual studies are limited by sample size and insufficient demographic diversity, so complex models of effect modification and subgroup differences in AD/ADRD risk have not been possible. In this proposal, we will use data from >19,700 individuals across 5 studies with up to 24 years of longitudinal clinical data and autopsy endpoints to definitively characterize the associations of TBI/RHI and AD/ADRD in the community. We will use advanced psychometric methods to harmonize key variables across cohorts and conduct integrative or coordinated analyses of individual patient data from all 5 studies. In Aim 1, we will test the association of TBI with clinically diagnosed dementia, including AD and other common neurodegenerative conditions such as dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). We also will evaluate common AD/ADRD endophenotypes including cognition, activities of daily living (ADLs), mood and motor function, and chronic disease comorbidity. In Aim 2, we will use neuropathological data from all 5 autopsy cohorts to test the association of TBI with pathologically confirmed AD, LBD, PD, and other ADRDs. We will also consider semi-quantitative and quantitative pathological endpoints that have been implicated as dementia-related neuropathology including measures of neurofibrillary tangles, diffuse and neuritic plaques, Lewy bodies, TDP-43 and vascular pathology. In both Aims 1 and 2, we will determine whether genetic risk loci associated with brain function and disease modify these associations. In Aim 3, we will determine the frequency of chronic traumatic encephalopathy (CTE) neuropathology, defined by consensus-derived diagnostic criteria, in the community. To date, research on CTE has been limited to highly selected cohorts of athletes, and little is known about the presence of CTE pathology or its relevance to AD/ADRD clinical outcomes in community-based settings. The proposed project stands to significantly advance scientific understanding of the complex associations of TBI/RHI and AD/ADRD. By leveraging data from multiple diverse cohort studies with extensive phenotypic data, results of this study will inform strategies for prevention, intervention development, and morbidity abatement for AD/ADRD.

项目摘要/摘要 这项R01建议：“利用现有的老化研究网络研究创伤性脑损伤（TBI） 和阿尔茨海默氏病（AD）和与AD相关痴呆（ADRD）风险”（Learn TBI＆AD）是为了回应 PAR 17-088要求对现有数据资源进行次要分析以解决临床老龄化研究 问题。在这个跨学科项目中，我们将使用最大的5个现有和新收集的数据 NIH资助的衰老研究（成人思想研究，宗教秩序研究，记忆和衰老 项目，少数族裔老化研究和弗雷明汉心脏研究），以检查TBI和 带有AD/ADRD的重复头部影响（RHI）。数十年来研究头部创伤之间的关系 痴呆症仍然没有定论；研究报告了矛盾的发现，但方法和方法差异 测量排除直接比较。单个研究受样本量和不足的限制 人口多样性，如此复杂的效果修改模型和AD/ADRD风险的亚组差异 不可能。在此提案中，我们将使用5个研究中的19,700个人的数据， 24年的纵向临床数据和尸检终点，以明确表征 TBI/RHI和社区中的AD/ADRD。我们将使用先进的心理测量方法来协调密钥 跨人群的变量，并对所有5个患者数据进行综合或协调分析 研究。在AIM 1中，我们将测试TBI与临床诊断的痴呆症的关联，包括AD和其他 常见的神经退行性疾病，例如Lewy身体（DLB）和帕金森氏病 （PD）。我们还将评估常见的AD/ADRD内部表型，包括认知，日常生活活动 （ADL），情绪和运动功能以及慢性病合并症。在AIM 2中，我们将使用神经病理学 来自所有5个尸检队列的数据，用于测试TBI与病理确认的AD，LBD，PD和 其他ADRD。我们还将考虑已经是半定量和定量病理终点 与实施相关的神经病理学，包括神经原纤维缠结，弥漫性和 神经斑块，路易尸体，TDP-43和血管病理学。在两个目标1和2中，我们将确定 与脑功能和疾病相关的遗传风险基因座是否改变了这些关联。在AIM 3中，我们 将确定慢性创伤性脑病（CTE）神经病理的频率，由 在社区中，共识衍生的诊断标准。迄今为止，对CTE的研究已限于高度 选定的运动员队列，对CTE病理学的存在或其与之相关的知之甚少 基于社区的环境中的广告/ADRD临床结果。拟议的项目大幅度 对TBI/RHI和AD/ADRD的复杂关联的科学理解。通过利用数据 来自多个潜水队队列研究，具有广泛的表型数据，这项研究的结果将为策略提供信息 用于预防，干预开发和AD/ADRD的发病率。