The Health & Aging Brain Study - Health Disparities (HABS-HD)

健康

• 批准号: 10493844
• 负责人: LEIGH A JOHNSON
• 金额: $ 2765.55万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493844
• 关键词: Aducanumab; Adult; Affect; African American; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Area; Biological; Biological Markers; Biostatistics Core; Blood; Blood Vessels; Clinic; Clinical; Clinical Trials; Communities; Complement; Data; Data Analyses; Development; Enrollment; Ensure; Environmental Risk Factor; Ethnic group; Etiology; Genetic; Genome; Goals; Guidelines; Health; Health Disparities Research; Hispanic; Hispanic Populations; Image; Individual; Inflammatory; Informatics; Life Cycle Stages; Liquid substance; Longitudinal cohort; Magnetic Resonance Imaging; Medical; Metabolic; Methods; Mexican Americans; Neuropsychology; Not Hispanic or Latino; Participant; Pathway interactions; Pharmaceutical Preparations; Population; Population Heterogeneity; Positron-Emission Tomography; Prevention strategy; Proteome; Research; Sampling; Science; Scientist; Structure; Therapeutic; Training; United States National Institutes of Health; Visit; aging brain; base; cohort; deprivation; exosome; experience; genomic data; health disparity; health goals; indexing; metabolome; neighborhood disadvantage; neuroimaging; next generation; novel; novel strategies; outreach; precision medicine; programs; racial and ethnic; recruit; social culture; social factors; tau Proteins; treatment strategy

HABS-HD OVERALL ABSTRACT The 2018 AT(N) framework provided the field with the first biological conceptualization of Alzheimer’s disease (AD) for the explicit purpose of advancing clinical trials. In fact, the first amyloid-lowering drug (aducanumab) has now received FDA clearance. However, nearly all data supporting the framework itself, as well as clinical trials, comes from research among non-Hispanic white (NHW) individuals. By 2060 the U.S. will become largely “non-white” with 15% of the population being African American (AA) and 27.5% being Hispanic (65% of which are Mexican American [MA]). Therefore, there is an urgent need to understand the relevance of the AT(N) framework, and associated biomarker-based therapeutics, for 43% of the U.S. population. AAs currently have the highest burden of AD and AD related dementias (ADRD) while Hispanics will experience the greatest increase in AD/ADRDs by 2060. Moreover, Milestone 1 of the NIA AD+ADRD Implementation Milestones explicitly call for examination of “early mechanistic pathways of multiple etiologies” (1.I), sociocultural (1.I) and exposome (1.B) factors among community-based cohorts that include cutting edge imaging, fluid, genetic and other biomarkers in diverse populations to understand health disparities in AD. The Health & Aging Brain Study – Health Disparities (HABS-HD) is the first large-scale, community-based project to simultaneously study each of the AT(N) defined biomarkers, in alignment with the NIA Health Disparities Research Framework, across the three most prevalent racial/ethnic groups in the U.S., AA, MA, and NHW. The Aims of the HABS-HD U19 are as follows: Aim 1: To collect imaging, clinical, biological and genetic data which will result in the largest longitudinal cohort of diverse populations that examines AT(N) biomarkers across adulthood. Aim 2: To collect life-course exposome (via the Area Deprivation Index), as well as sociocultural data and examine how these factors affect the timing, sequence and trajectories of AT(N) biomarkers among diverse populations. Aim 3: To disseminate HABS-HD data and samples to the global scientific community. HABS-HD data will be made available via LONI while biofluid samples will be made available through the HABS-HD Omics Core. Genomics data will be made available per NIH/NIA guidelines. The long-term goal of HABS-HD is to establish population- specific informed precision medicine for novel treatment and prevention strategies for AD. To advance this goal, we will conduct the following Projects: Project 1) Examine the timing, sequence and trajectories of AT(N) biomarkers across diverse populations; Project 2) Examine the impact of vascular, metabolic and inflammatory factors on the timing, sequence and trajectories of AT(N) biomarkers across diverse populations; and Project 3) Examine the impact of the exposome (via neighborhood disadvantage) and sociocultural factors on the timing, sequence and trajectories of AT(N) biomarkers across diverse populations.

HABS-HD 总体摘要 2018 年 AT(N) 框架为该领域提供了第一个阿尔茨海默病的生物学概念 (AD) 出于推进临床试验的明确目的。事实上，第一种降低淀粉样蛋白的药物（aducanumab） 现已获得 FDA 批准。然而，几乎所有支持框架本身的数据以及临床数据 试验来自对非西班牙裔白人 (NHW) 个体的研究。到 2060 年，美国将成为 大部分是“非白人”，其中 15% 的人口是非裔美国人 (AA)，27.5% 是西班牙裔（65% 他们是墨西哥裔美国人 [MA]）。因此，迫切需要了解其相关性 AT(N) 框架以及相关的基于生物标志物的治疗方法，适用于 43% 的美国人口。目前AA 患有 AD 和 AD 相关痴呆症 (ADRD) 的负担最高，而西班牙裔则经历的负担最重 到 2060 年 AD/ADRD 数量将增加。此外，NIA AD+ADRD 实施里程碑的里程碑 1 明确呼吁检查“多种病因的早期机制途径”（1.I）、社会文化（1.I）和 基于社区的队列中的暴露组 (1.B) 因素，包括尖端成像、体液、遗传和 不同人群中的其他生物标志物，以了解 AD 的健康差异。健康与衰老的大脑 研究 – 健康差异 (HABS-HD) 是第一个同时研究的大型社区项目 AT(N) 定义的每个生物标志物均符合 NIA 健康差异研究框架， 跨越美国三个最普遍的种族/族裔群体：AA、MA 和 NHW。 HABS-HD 的目标 U19 的目标如下： 目标 1：收集影像、临床、生物和遗传数据，从而得出 最大的不同人群纵向队列，检查整个成年期的 AT(N) 生物标志物。目标 2： 收集生命历程暴露组（通过区域剥夺指数）以及社会文化数据并研究如何 这些因素影响不同人群中 AT(N) 生物标志物的时间、序列和轨迹。目的 3：向全球科学界传播 HABS-HD 数据和样本。将制作HABS-HD数据 生物流体样本将通过 HABS-HD Omics Core 提供。基因组学 数据将根据 NIH/NIA 指南提供。 HABS-HD 的长期目标是建立人口- 针对 AD 的新型治疗和预防策略的具体知情精准医学。为了推进这个 为了实现这一目标，我们将进行以下项目： 项目 1) 检查 AT(N) 的时间、顺序和轨迹 不同人群的生物标志物；项目2）检查血管、代谢和炎症的影响 影响不同人群中 AT(N) 生物标志物的时间、序列和轨迹的因素；及项目 3）检查暴露组（通过邻里劣势）和社会文化因素对 不同人群中 AT(N) 生物标志物的时间、序列和轨迹。