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（AAs）目前遭受阿尔茨海默病（AD）和阿尔茨海默病（AD）的最高负担。 疾病相关性痴呆（ADRD），而西班牙裔（其中65%是墨西哥裔美国人[MA]）将 到2060年，疾病负担将出现最大幅度的增长。此外，新数据支持种族/族裔 淀粉样蛋白（A）、Tau（T）和神经变性（N）的基本病理学生物标志物在 AD，由2018年AT（N）框架（项目1）定义。研究还表明， 血管、代谢和炎症（VMI）因素对AD结局的影响，这些因素的发生率较高 在AA和MA之间，因此可能影响AT（N）生物标志物（项目2）。鉴于AA和MA 经历了以前与AD结果相关的麻烦和社会文化因素的不同负担，这些 这些因素可能导致观察到的AD健康差异和生物标志物差异。事实上，Link & Duman “根本原因论”提出，社会因素可能是疾病的“根本原因”， 考虑成功的干预策略。NIA AD + ADRD的Milestone 1.B和1.I 《执行千年宣言》明确要求审查麻烦和社会因素对 AD/ADRD差异。因此，项目3将评估麻烦的影响（即，邻域 不利条件）和社会文化（即，文化适应，压力，种族主义）因素对 认知能力下降的患病率、顺序和轨迹以及AT（N）定义的生物标志物， 因此，项目3将解决以下具体问题 目标与NIA健康差异研究框架保持一致。目标1：检查 邻里劣势和社会文化因素对认知障碍的存在和纵向进展的影响 非裔美国人，墨西哥裔美国人和非西班牙裔白人的损失。目标2：审查 邻里劣势和社会文化因素对AT（N）的存在、序列和轨迹的影响 在非裔美国人、墨西哥裔美国人和非西班牙裔白人中定义生物标志物。目标3：检查 表观遗传因素对邻里劣势和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。 西班牙裔白人目标4（项目-项目互动）：与项目1和2合作， 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 作为对其他研究的比较，研究了邻里劣势的影响（例如， 社区研究）和社会文化因素（例如，WHICAP，SOL/印加CA），对AD生物标志物和认知功能的影响 轨迹