HABS-HD - Project 3

HABS-HD项目3摘要 非裔美国人(AA)目前遭受阿尔茨海默病(AD)和阿尔茨海默氏症的最大负担 疾病相关性痴呆症(ADRD)，而西班牙裔(其中65%是墨西哥裔美国人[MA])将 到2060年，经历疾病负担最大的增长。此外，新兴数据支持种族/民族 阿尔茨海默病患者淀粉样蛋白(A)、牛磺酸(T)和神经变性(N)基础病理标志物的差异 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转归的影响，其发生率较高 因此，可能会影响AT(N)生物标志物(项目2)。鉴于AAS和MAS 经历与AD结果相关的暴露因素和社会文化因素的不同负担，这些 可观察到的阿尔茨海默病健康差异和生物标志物差异的因素可能起作用。事实上，The Link&Phelan “根本原因说”提出，社会因素可能是疾病的“根本原因”，而且必须是 被认为是成功的干预策略。NIA AD+ADRD的里程碑1.B和1.I 实施里程碑明确要求审查暴露和社会因素对 AD/ADRD差异。因此，项目3将评估Exposome(即，邻居)的影响 不利因素)和社会文化因素(即，适应文化、压力、感受到的种族主义) 认知功能减退的患病率、顺序和轨迹以及AT(N)定义的生物标志物 美国最大的三个种族/民族。因此，项目3将解决以下具体问题 旨在与NIA健康差异研究框架保持一致。目标1：检查两者之间的联系 邻里劣势和社会文化因素对认知存在和纵向发展的影响 在非洲裔美国人、墨西哥裔美国人和非西班牙裔白人中的损失。目标2：检查以下方面的影响 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 在非裔美国人、墨西哥裔美国人和非西班牙裔白人中定义了生物标志物。目标3：检查 表观遗传因素对邻里劣势与社会文化因素关系的影响 AT(N)定义的生物标志物和认知轨迹，在非洲裔美国人、墨西哥裔美国人和非 西班牙裔白人。目标4(项目-项目交互)：与项目1和项目2协作，制定 全面了解不同人群中AT(N)定义的生物标记物。目标5：利用数据 来自项目3，作为与检查邻里劣势的影响的其他研究的比较(例如， 社区研究)和社会文化因素(如WHICAP、SOL/INCA)对AD生物标志物和认知的影响 轨迹。

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.