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

基本信息

批准号：
10064985
负责人：
Kristen Dams-O'Connor
金额：
$ 105.78万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/10064985
关键词：
Abate Activities of Daily Living Address Adult Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos 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 Diagnostic 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 Parkinson&apos s Dementia Participant Pathologic Pathology 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 apolipoprotein E-4 base chronic traumatic encephalopathy clinical Diagnosis cohort comorbidity contact sports data resource dementia risk 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

项目摘要

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.

项目概要/摘要 R01 提案“利用现有的衰老研究网络来调查创伤性脑损伤 (TBI)” 以及阿尔茨海默病 (AD) 和 AD 相关痴呆 (ADRD) 风险”（LEARN TBI & AD），是为了应对 PAR 17-088 要求对现有数据资源进行二次分析以解决临床衰老研究在这个跨学科项目中，我们将使用来自 5 个最大的现有数据和新收集的数据。 NIH 资助的衰老研究（成人思想变化研究、宗教秩序研究、记忆与衰老项目（少数族裔老龄化研究和弗雷明汉心脏研究），旨在研究 TBI 与重复性头部撞击 (RHI) 与 AD/ADRD 之间的关系进行了数十年的研究。痴呆症仍然没有定论；研究结果相互矛盾，但方法和方法存在差异。测量结果无法进行直接比较。个别研究受到样本量和不足的限制。人口多样性，因此影响修正的复杂模型和 AD/ADRD 风险的亚组差异在这项提案中，我们将使用来自 5 项研究中超过 19,700 人的数据。 24 年的纵向临床数据和尸检终点，明确描述了以下因素之间的关联：我们将使用先进的心理测量方法来协调社区中的 TBI/RHI 和 AD/ADRD。跨队列的变量并对所有 5 个患者的个体数据进行综合或协调分析在目标 1 中，我们将测试 TBI 与临床诊断的痴呆症（包括 AD 和其他疾病）的关联。常见的神经退行性疾病，例如路易体痴呆 (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 与病理证实的 AD、LBD、PD 和我们还将考虑已确定的半定量和定量病理终点。涉及痴呆相关的神经病理学，包括神经原纤维缠结、弥漫性和神经原纤维缠结的测量神经炎斑块、路易体、TDP-43 和血管病理学在目标 1 和 2 中，我们将确定。在目标 3 中，我们研究与大脑功能和疾病相关的遗传风险位点是否会改变这些关联。将确定慢性创伤性脑病 (CTE) 神经病理学的频率，定义为迄今为止，社区对 CTE 的研究仅限于高度共识的诊断标准。选定的运动员群体，对 CTE 病理学的存在或其相关性知之甚少拟议的项目在社区环境中具有显着的临床效果。通过利用数据对 TBI/RHI 和 AD/ADRD 复杂的高级关联进行科学理解。来自具有广泛表型数据的多个不同队列研究，这项研究的结果将为策略提供信息用于 AD/ADRD 的预防、干预措施开发和发病率降低。