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

摘要 在我们老龄化的人口中预防阿尔茨海默氏症和认知能力下降是一项重大的公共健康 优先考虑。与其他种族相比，老年黑人患阿尔茨海默氏症的负担不成比例 和种族群体。负担增加的原因是未知的和传统的因素，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距。两项重要研究 需要方向来填补目前关于阿尔茨海默氏症和认知能力下降的知识空白 对于老年黑人成年人来说，这是我们老年人口中最脆弱的部分之一。第一，收集的研究 来自有足够认知跟踪的特征良好的老年黑人的死前和死后生物标本是 需要促进我们对痴呆症背后的病理基础的理解。第二， 调查与黑人生活经历有关的新因素对于确定新的目标是至关重要的 用于干预、政策和治疗。新冠肺炎对黑人的毁灭性影响加上 人们对结构性种族主义相互关联的系统的认识不断提高，使人们认识到 种族特有的压力是一个未被充分研究的风险因素。众所周知，一般的压力有消极的作用。 对老年黑人的心理和身体健康的影响，但很少有研究考察 种族特有的压力对大脑健康的影响。拟议延续少数群体老龄化的总体目标 研究研究(MARS)是衡量个人和环境层面的种族特定压力源，并确定 将它们与晚年认知衰退、阿尔茨海默病事件和其他健康状况不佳联系在一起的生物机制 老龄化的后果。利用来自另外两项正在进行的研究的统一的临床和神经病理数据 在拉什，我们将把黑人的样本规模增加到1200多人，以满足新的具体目标。 我们建议继续收集MARS参与者的临床和尸检数据，测试 新的种族特定应激源与认知能力下降和AD有关，并量化炎症和血管病理 分别在血液和大脑中测试两条潜在的生物通路，将压力与老年人的大脑健康联系起来 黑人。目标1将考察个体和环境种族特有的压力源之间的关系 阿尔茨海默病事件与认知功能下降。Aim 2将利用Medicare索赔数据来检查 这些应激源与其他慢性血管相关的健康状况有关。AIM 3将使用蛋白质组学来测量 血浆中的炎性蛋白，并检测它们与应激源和AD的关系。最后，目标4将 检查应激源与脑血管神经病变和小胶质细胞的关系，以及 测试这些病理是否解释了种族特有的压力与阿尔茨海默病的关联。建议进行的研究 提供了一个独特的机会来回答关于我们老龄化研究不足的一大部分的关键问题 并结合了尚未在临床-神经病理学中检查的种族特有的风险因素 学习。

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.