Racial Differences in Late-Life Cognitive decline and risk of Alzheimer's Disease

摘要 预防老年痴呆症和认知能力下降是我国老年人口的一项重大公共卫生工作 要务与其他种族相比，老年黑人成年人患阿尔茨海默氏症的负担不成比例。 和种族群体。负担增加的原因尚不清楚，传统因素包括血管， 社会经济和医疗保健利用率并不能完全解释这种差异。两个重要研究 需要方向来填补目前关于阿尔茨海默氏症痴呆和认知能力下降的知识空白 黑人老年人是我们老年人口中最脆弱的群体之一。第一，研究收集 来自具有充分认知随访的特征良好的老年黑人的生前和死后生物标本， 需要进一步了解痴呆症的病理基础。二是 对与黑人生活经历密切相关的新因素进行调查，对于确定新的目标至关重要 for intervention干预，policy政策，and therapeutics治疗. COVID-19对黑人的破坏性影响， 对结构性种族主义相互关联的系统的认识有所提高，使人们注意到， 种族特有的压力作为一个未充分研究的风险因素。有充分的证据表明，一般的压力有负面影响， 对老年黑人的心理和身体健康的影响，但很少有研究探讨了 种族特有的压力对大脑健康的影响建议继续实施少数民族老龄化的总体目标 研究性学习（MARS）旨在测量个体和环境层面的种族特异性压力源， 将其与晚年认知能力下降、AD事件和其他健康状况不佳联系起来的生物学机制 老龄化的结果。利用其他两项正在进行的研究的协调临床和神经病理学数据 在拉什，我们将增加我们的黑人样本量超过1200人，以解决新的具体目标。 我们建议继续收集MARS参与者的临床和尸检数据，测试 新的种族特异性应激源与认知能力下降和AD，并量化炎症和血管病理 分别在血液和大脑中，以测试两种潜在的生物学途径，将压力与老年人的大脑健康联系起来。 黑人目标1将研究个体和环境种族特异性压力源之间的关系， AD和认知能力下降。目标2将利用医疗保险索赔数据来检查 这些压力源与其他慢性血管相关的健康状况。目标3将采用蛋白质组学来测量 血浆中的炎性蛋白，并检查它们与应激源和AD的关联。最后，Aim 4将 检查压力源与血管神经病理学和大脑中测量的小胶质细胞的关联， 测试这些病理学是否解释了种族特异性应激与AD的关联。拟定研究 提供了一个独特的机会来回答关于我们老龄化的一个大的未充分研究的部分的关键问题 社会，并纳入种族特异性的风险因素，尚未在临床神经病理检查 问题研究

ABSTRACT The prevention of Alzheimer’s dementia and cognitive decline in our aging population is a major public health priority. Older Black adults are disproportionately burdened by Alzheimer’s dementia compared to other racial and ethnic groups. Reasons for the increased burden are unknown and traditional factors, including vascular, socioeconomic, and healthcare utilization, do not fully account for the disparity. Two important research directions are needed to fill the current gap in knowledge regarding Alzheimer’s dementia and cognitive decline for older Black adults, one of the most vulnerable segments of our older population. First, studies which collect ante- and postmortem biospecimens from well-characterized older Blacks with sufficient cognitive follow-up are needed to advance our understanding of the pathologic substrates underlying dementia. Second, the investigation of novel factors uniquely tied to the lived experience of Blacks is essential to identify new targets for intervention, policy, and therapeutics. The devastating effects of COVID-19 on Blacks coupled with the increased awareness of interrelated systems of structural racism, have shone a spotlight on the importance of race-specific stress as an understudied risk factor. It is well-documented that general stress has a negative impact on the psychological and physical health of older Blacks, but few studies have examined the impact of race-specific stress on brain health. The overall goal of the proposed continuation of the Minority Aging Research Study (MARS) is to measure individual- and environmental-level race-specific stressors and identify the biologic mechanisms linking them to late-life cognitive decline, incident AD, and other poor health outcomes in aging. Leveraging harmonized clinical and neuropathological data from two other ongoing studies at Rush, we will increase our sample size of Blacks to more than 1200 persons to address new Specific Aims. We propose to continue collecting clinical and postmortem data on MARS participants, test the association of novel race-specific stressors with cognitive decline and AD, and quantify inflammation and vascular pathology in blood and brain, respectively, to test two potential biologic pathways linking stress to brain health in older Blacks. Aim 1 will examine the relationship between individual and environmental race-specific stressors with incident AD and cognitive decline. Aim 2 will leverage Medicare claims data to examine the relationship of these stressors with other chronic vascular-related health conditions. Aim 3 will employ proteomics to measure inflammatory proteins in plasma and examine their association with stressors and AD. Finally, Aim 4 will examine the association of stressors with vascular neuropathologies and microglia measured in the brain, and test whether these pathologies account for the association of race-specific stress with AD. The proposed study provides a unique opportunity to answer critical questions about a large understudied segment of our aging society and incorporates race-specific risk factors that have not been examined in clinical-neuropathologic studies.