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: 9891932
• 负责人: Kristen Dams-O'Connor
• 金额: $ 110.98万
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891932
• 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; Diagnosis; Diagnostic; Disease; Elderly; Environmental Risk Factor; Epidemiology; Evaluation; Framingham Heart Study; Frequencies; Funding; Genetic; Genetic Risk; Genotype; Incidence; Individual; Investigation; Lewy Bodies; Lewy Body Dementia; Longitudinal Studies; Longitudinal cohort study; Measurement; Measures; Memory; Meta-Analysis; Metadata; Methodology; Methods; Military Personnel; Minority; Modeling; Modernization; Modification; Moods; Morbidity - disease rate; Motor; Nerve Degeneration; Neurodegenerative Disorders; Neurofibrillary Tangles; Outcome; Parkinson Disease; Parkinson' s Dementia; Participant; Pathologic; Pathology; Prevention strategy; Preventive Intervention; Process; Psychometrics; Reporting; Research; Risk; Risk Factors; Role; Sample Size; Sampling; Scanning; Scientific Advances and Accomplishments; Senile Plaques; Services; Slide; Sports; Subgroup; Testing; Traumatic Brain Injury; United States National Institutes of Health; Work; alpha synuclein; analytical method; apolipoprotein E-4; base; chronic traumatic encephalopathy; clinical Diagnosis; cohort; comorbidity; data resource; dementia risk; digital; endophenotype; epidemiology study; genetic risk factor; genomic locus; head impact; improved; indexing; individual patient; lifestyle factors; longitudinal design; 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.

项目总结/摘要 R 01提案，“利用现有的老龄化研究网络来调查创伤性脑损伤（TBI）” 和阿尔茨海默病（AD）和AD相关痴呆（ADRD）风险”（LEARN TBI & AD），是对 PAR 17-088要求对现有数据资源进行二次分析，以解决临床老化研究问题 问题.在这个跨学科的项目中，我们将使用现有的和新收集的数据，从5个最大的 美国国立卫生研究院资助的衰老研究（成人思想变化研究，宗教秩序研究，记忆和衰老 项目，少数民族老龄化研究和心脏病研究），以检查TBI和 AD/ADRD的重复性头部撞击（RHI）。几十年来关于头部创伤与 和痴呆症仍然没有定论;研究报告了相互矛盾的结果，但方法和 测量排除了直接比较。个体研究受样本量限制， 人口统计学多样性，因此AD/ADRD风险的效应修正和亚组差异模型复杂 是不可能的在本提案中，我们将使用来自5项研究中> 19，700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AD/ADRD。我们将使用先进的心理测量方法， 变量，并对所有5个队列的个体患者数据进行综合或协调分析 问题研究在目标1中，我们将测试TBI与临床诊断的痴呆症（包括AD和其他痴呆症）的相关性。 常见的神经退行性疾病，如路易体痴呆（DLB）和帕金森病 （PD）。我们还将评估常见的AD/ADRD内表型，包括认知、日常生活活动 （ADL）、情绪和运动功能以及慢性疾病合并症。在目标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，以测试TBI与病理学证实的AD、LBD、PD和 其他ADRD我们还将考虑已被证实的半定量和定量病理终点。 涉及痴呆相关的神经病理学，包括神经系统缠结、弥漫性和 神经炎斑块、路易体、TDP-43和血管病理学。在目标1和2中，我们将确定 与脑功能和疾病相关的遗传风险位点是否改变了这些关联。在目标3中，我们 将确定慢性创伤性脑病（CTE）神经病理学的频率，定义为 在社区中，共识衍生的诊断标准。迄今为止，对CTE的研究仅限于高度 选择的运动员队列，并且对CTE病理的存在或其与 AD/ADRD在社区环境中的临床结局。拟议的项目具有重大意义 促进对TBI/RHI和AD/ADRD复杂关联的科学理解。通过利用数据 从具有广泛表型数据的多个不同队列研究中，本研究的结果将为策略提供信息 用于AD/ADRD的预防、干预开发和发病率降低。