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

晚年认知能力下降和阿尔茨海默病风险的种族差异

• 批准号: 10472588
• 负责人: Lisa L Barnes
• 金额: $ 228.17万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10472588
• 关键词: Address; Adult; African American; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Atherosclerosis; Autopsy; Awareness; Behavior; Biological; Black Populations; Black race; Blood; Blood Vessels; Brain; Brain Pathology; COVID-19; COVID-19 impact; Cardiovascular Diseases; Cerebral Amyloid Angiopathy; Chronic; Clinical; Cognition; Cognitive; Cohort Studies; Coupled; Data; Data Collection; Dementia; Discrimination; Disease; Elderly; Epidemiology; Ethnic group; Funding; Goals; Health; Impaired cognition; Individual; Infarction; Inflammation; Inflammatory; Intervention; Investigation; Knowledge; Lead; Link; Measures; Medicare claim; Memory; Mental Health; Microglia; Minority; Neighborhoods; Neurobiology; Older Population; Outcome; Participant; Pathologic; Pathology; Pathway interactions; Pattern; Persons; Physical activity; Plasma; Policies; Population; Prevention; Proteins; Proteomics; Protocols documentation; Psychological Impact; Race; Reproducibility; Research; Resources; Risk Factors; Sample Size; Shelter facility; Social Impacts; Societies; Source; Stress; Structural Racism; System; Testing; Therapeutic; Violence; aging population; brain health; brain tissue; cohort; dementia risk; density; disparity reduction; experience; follow-up; health care availability; health care service utilization; health disparity; hospitalization rates; neuropathology; novel; pandemic disease; physical conditioning; public health priorities; racial difference; racial disparity; ranpirnase; research study; residential segregation; social vulnerability; socioeconomics; stressor; vascular inflammation; vascular risk factor

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.

抽象的 预防老年痴呆症和老年人认知能力下降是一项重大公共卫生问题 优先事项。与其他种族相比，老年黑人患阿尔茨海默氏症的比例更高 和族裔群体。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并不能完全解释这种差异。两项重要研究 需要方向来填补当前有关阿尔茨海默氏痴呆和认知能力下降的知识空白 对于老年黑人来说，他们是老年人口中最脆弱的群体之一。一、研究收集 来自经过充分认知随访的特征良好的老年黑人的死前和死后生物样本 需要增进我们对痴呆症病理基础的理解。其次， 对与黑人生活经历独特相关的新因素的调查对于确定新目标至关重要 干预、政策和治疗。 COVID-19 对黑人的毁灭性影响以及 人们对结构性种族主义相互关联系统的认识不断提高，使人们更加关注 种族特定的压力作为一个未被充分研究的风险因素。有充分证据表明，一般压力具有负面影响 对老年黑人心理和身体健康的影响，但很少有研究探讨 种族特定的压力对大脑健康的影响。拟议继续少数族裔老龄化的总体目标 研究 (MARS) 旨在测量个人和环境层面的种族特定压力源并识别 将它们与晚年认知能力下降、AD 事件和其他不良健康状况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统一临床和神经病理学数据 在 Rush，我们将把黑人样本数量增加到 1200 人以上，以实现新的具体目标。 我们建议继续收集 MARS 参与者的临床和尸检数据，测试以下因素之间的关联： 与认知能力下降和 AD 相关的新型种族特异性压力源，并量化炎症和血管病理学 分别在血液和大脑中测试两种将压力与老年人大脑健康联系起来的潜在生物途径 黑人。目标 1 将检查个人和环境种族特定压力源之间的关系 AD 事件和认知能力下降。目标 2 将利用 Medicare 索赔数据来检查以下关系： 这些压力源与其他慢性血管相关的健康状况有关。目标 3 将采用蛋白质组学来测量 血浆中的炎症蛋白并检查它们与压力源和 AD 的关系。最后，目标 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，以及 测试这些病理学是否可以解释种族特异性压力与 AD 之间的关联。拟议的研究 提供了一个独特的机会来回答有关我们老龄化中大部分未被研究的部分的关键问题 社会并纳入了尚未在临床神经病理学中检查过的种族特定危险因素 研究。