Historical social and environmental determinants of memory decline and dementia among U.S. older adults.

项目摘要/摘要 与黑人相比，阿尔茨海默病和相关痴呆(ADRD)的发病率在黑人中高出40%-100% 和美国白人在一起。造成这种差异的一个关键原因可能包括居住在隔离的、社会不利的地区- 停滞不前，污染严重的社区。现有的研究表明，社区的社会经济剥夺与 脑体积减少，阿尔茨海默氏症的神经病理，认知功能低下，以及细小的颗粒物 物质(PM2.5)可能会导致神经退化。早期接触可能特别重要，因为 早期生活社区水平的劣势和环境空气污染可能会扰乱认知能力的积累 保留、降低认知韧性，并抑制社交轨迹。社区层面的社会因素和空气 污染往往同时发生；因此，全面了解这些因素是如何独立和 协同效应需要对两者进行严格的评估。此外，确定这些因素在多大程度上 修改潜在的遗传风险--APOE-ε4基因型和ADRD多基因风险得分--将在以下方面提供信息- 对ADRD病因学的认识。这项应用的总体目标是评估早期生活的效果 社区层面的社会和环境因素对老年ADRD的影响以及这些因素对ADRD的影响程度。 在具有全国代表性的样本中致敬ADRD上的种族差异。中心假设是早期- 生活社区层面的社会因素和环境空气污染对晚更生的影响是独立的和协同的。 生命、大脑健康和ADRD差异。 该项目利用了最近完成的1940年人口普查和国民健康之间的数据联系 和退休研究(HRS)(n≈8,700)。HRS的参与者最初的平均年龄为69岁 1995-1998年间的记忆评估，因此HRS包括长达23年的关于记忆的纵向数据 分数和痴呆症，一个子样本也有基因信息。核心假设将在#年进行检验。 黑人和白人HRS参与者的四个具体目标：(1)调查早期生活社区的影响- 层面的社会因素对晚年认知健康的影响；(2)考察早年环境空气污染博览会的影响- 对晚年认知健康的肯定；(3)估计早期生活社区层面的社会因素和 空气污染暴露对晚年认知健康的影响；以及(4)评估早期社区- 水平、社会因素和环境空气污染可改变ADRD遗传风险对老年认知的影响。 动感健康。这项拟议的研究具有创新性，因为它评估了早期生命、社会和环境的联合 社区层面的暴露，包括通过新的空气污染指标和20世纪30年代末的红线，为ADRD。这个 拟议的工作有望通过提供有关潜在战略的新的与政策相关的证据来推动该领域的发展。 预防ADRD和消除ADRD差异的GES。

PROJECT SUMMARY/ABSTRACT Incidence of Alzheimer’s disease and related dementias (ADRD) is 40–100% higher among Black compared with White Americans. A key reason for this disparity may include residence in segregated, socially disadvan- taged, and polluted communities. Extant studies suggest that community socioeconomic deprivation is related to decreased brain volume, Alzheimer’s neuropathology, and poor cognitive function, and that fine particulate matter (PM2.5) may contribute to neurodegeneration. Early-life exposures may be particularly important, as early-life community-level disadvantage and ambient air pollution could disrupt the accumulation of cognitive reserve, reduce cognitive resilience, and dampen social trajectories. Community-level social factors and air pollution often co-occur; thus, comprehensive understanding of how these factors operate independently and synergistically requires rigorous evaluation of both. Moreover, identifying the extent to which these factors modify underlying genetic risk—APOE-ε4 genotype and ADRD polygenic risk scores—would inform under- standing of the etiology of ADRD. The overall objective of this application is to evaluate the effects of early-life community-level social and environmental factors on late-life ADRD and the extent to which these factors con- tribute to racial disparities on ADRD in a nationally representative sample. The central hypothesis is that early- life community-level social factors and ambient air pollution have independent and synergistic effects on late- life brain health and ADRD disparities. This project leverages the recently completed data linkage between the 1940 census and the national Health and Retirement Study (HRS) (n≈8,700). Participants in the HRS were an average age of 69 years at first memory assessment between 1995–1998, so HRS includes up to 23 years of longitudinal data on memory scores and dementia, and a subsample also has genotype information. The central hypothesis will be tested in four specific aims among Black and White HRS participants: (1) Investigate the effects of early-life community- level social factors on late-life cognitive health; (2) Examine the effects of early-life ambient air pollution expo- sure on late-life cognitive health; (3) Estimate synergistic effects of early-life community-level social factors and air pollution exposure on late-life cognitive health; and (4) Evaluate the extent to which early-life community- level social factors and exposure to ambient air pollution modify effects of ADRD genetic risk on late-life cogni- tive health. The proposed research is innovative because it assesses joint early-life social and environmental community-level exposures, including via novel air pollution metrics and late-1930s redlining, for ADRD. The proposed work is expected to advance the field by providing new policy-relevant evidence on potential strate- gies to prevent ADRD and eliminate ADRD disparities.