HABS-HD - Project 3

HABS-HD - 项目 3

• 批准号: 10708902
• 负责人: Sid E O'Bryant
• 金额: $ 52.41万
• 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/10708902
• 关键词: Acculturation; African American population; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Area; Autopsy; Biological; Biological Markers; Blood Vessels; Childhood; Cognition; Cognitive; Collaborations; Data; Disease; Disease Outcome; Disparate; Disparity; Epigenetic Process; Ethnic Population; Health; Health Disparities Research; Hispanic Populations; Household; Impaired cognition; Income; Inflammation; Inflammatory; Intervention; Language; Lead; Link; Magnetic Resonance Imaging; Measures; Memory; Metabolic; Metabolic dysfunction; Mexican Americans; Neighborhoods; Nerve Degeneration; Not Hispanic or Latino; Outcome; Pathologic; Plasma; Population Heterogeneity; Prevalence; Race; Research; Research Personnel; Risk; Stress; aging brain; burden of illness; cognitive function; deprivation; epigenetic marker; ethnic difference; executive function; experience; health disparity; indexing; magnetic resonance imaging biomarker; methylation pattern; middle age; neighborhood disadvantage; neuropathology; racial difference; racial population; racism; residential segregation; social culture; social factors; sociocultural determinant; successful intervention; tau Proteins; theories; trend

HABS-HD PROJECT 3 ABSTRACT African Americans (AAs) currently suffer the highest burden of Alzheimer’s disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) while Hispanics (65% of which are Mexican American [MA]) will experience the greatest increase in disease burden by 2060. Additionally, emerging data supports racial/ethnic differences in the fundamental pathological biomarkers of Amyloid (A), Tau (T), and Neurodegeneration (N) in AD, as defined by the 2018 AT(N) framework (Project 1). Research also demonstrates a significant impact of vascular, metabolic and inflammatory (VMI) factors on AD outcomes, which are experienced at higher rates among AAs and MAs and, therefore, may impact AT(N) biomarkers (Project 2). Given that AAs and MAs experience a disparate burden of exposome and sociocultural factors previously linked to AD outcomes, these factors may contribute to observed AD health disparities and biomarker differences. In fact, the Link & Phelan “Fundamental Causes Theory” proposes that social factors may be ‘fundamental causes’ of disease and must be considered for successful intervention strategies. Milestones 1.B and 1.I of the NIA AD + ADRD Implementation Milestones explicitly call for examinations of the impact of exposome and social factors on AD/ADRD disparities. Therefore, Project 3 will evaluate the impact of exposome (i.e., neighborhood disadvantage) and sociocultural (i.e., acculturation, stress, perceived racism) factors on the prevalence, sequence and trajectories of cognitive decline as well as AT(N) defined biomarkers among the three largest racial/ethnic groups in the U.S. Therefore, Project 3 will address the following Specific Aims in alignment with the NIA Health Disparities Research Framework. Aim 1: Examine the link between neighborhood disadvantage and sociocultural factors on the presence and longitudinal progression of cognitive loss among African Americans, Mexican Americans and non-Hispanic whites. Aim 2: Examine the impact of neighborhood disadvantage and sociocultural factors on the presence, sequence and trajectories of AT(N) defined biomarkers among African Americans, Mexican Americans and non-Hispanic whites. Aim 3: Examine the impact of epigenetic factors on the link between neighborhood disadvantage and sociocultural factors on AT(N) defined biomarkers, and cognitive trajectories, among African Americans, Mexican Americans and non- Hispanic whites. Aim 4 (Project – Project Interactions): Collaborate with Projects 1 and 2 to develop a comprehensive understanding of AT(N) defined biomarkers across diverse populations. Aim 5: Utilize data from Project 3 as a comparison for other studies examining the impact of neighborhood disadvantage (e.g., Neighborhood Study), and sociocultural factors (e.g., WHICAP, SOL/INCA), on AD biomarkers and cognitive trajectories.

HABS-HD 项目 3 摘要 非裔美国人 (AA) 目前遭受阿尔茨海默病 (AD) 和阿尔茨海默病的负担最高 疾病相关痴呆症 (ADRD)，而西班牙裔人（其中 65% 是墨西哥裔美国人 [MA]）会 到 2060 年，疾病负担将出现最大增幅。此外，新出现的数据支持种族/族裔 淀粉样蛋白 (A)、Tau (T) 和神经退行性变 (N) 等基本病理生物标志物的差异 2018 AT(N) 框架（项目 1）定义的 AD 也显示出显着影响。 血管、代谢和炎症 (VMI) 因素对 AD 结局的影响较高 AA 和 MA 之间的差异，因此可能会影响 AT(N) 生物标志物（项目 2）。 经历了先前与AD结果相关的暴露组和社会文化因素的不同负担，这些 事实上，Link & Phelan 认为，一些因素可能会导致观察到的 AD 健康差异和生物标志物差异。 “根本原因论”提出，社会因素可能是疾病的“根本原因”，必须加以解决。 考虑 NIA AD + ADRD 的成功干预策略的里程碑 1.B 和 1.I。 实施里程碑明确要求检查暴露和社会因素对 因此，项目 3 将评估暴露组（即邻域）的影响。 劣势）和社会文化（即文化适应、压力、感知的种族主义）因素 认知衰退的患病率、顺序和轨迹以及 AT(N) 生物标志物定义 美国三个最大的种族/族裔群体因此，项目 3 将解决以下具体问题 目标与 NIA 健康差异研究框架一致 目标 1：检查之间的联系。 邻里劣势和社会文化因素对存在和纵向发展的影响 目标 2：考察非裔美国人、墨西哥裔美国人和非西班牙裔白人的损失。 邻里劣势和社会文化因素对 AT(N) 的存在、顺序和轨迹的影响 目标 3：检查非裔美国人、墨西哥裔美国人和非西班牙裔白人的生物标志物。 表观遗传因素对邻里劣势与社会文化因素之间联系的影响 AT(N) 定义了非裔美国人、墨西哥裔美国人和非裔美国人的生物标志物和认知轨迹 目标 4（项目 - 项目互动）：与项目 1 和 2 合作开发 全面了解不同人群中 AT(N) 定义的生物标志物。目标 5：利用数据。 来自项目 3，作为与其他研究邻里劣势影响的研究的比较（例如， 邻里研究）和社会文化因素（例如 WHICAP、SOL/INCA）对 AD 生物标志物和认知的影响 轨迹。