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

美国老年人记忆力下降和痴呆症的历史社会和环境决定因素

• 批准号: 10824083
• 负责人: Joan A Casey
• 金额: $ 61.6万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10824083
• 关键词: Affect; Age; Air Pollution; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Area; Black American; Black Populations; Black race; Brain; Buffers; Censuses; Child; Classification; Cognitive; Communities; Data; Data Linkages; Dementia; Development; Disparity; Education; Elderly; Environment; Environmental Hazards; Environmental Risk Factor; Etiology; Evaluation; Exposure to; Genetic Risk; Genotype; Health; Health and Retirement Study; Impaired cognition; Incidence; Individual; Infant; Institutional Racism; Joints; Life; Life Experience; Link; Maps; Measures; Memory; Memory Loss; Modeling; Neighborhoods; Nerve Degeneration; Outcome; Participant; Pathology; Play; Policies; Pollution; Population; Prevalence; Public Health; Race; Recording of previous events; Records; Research; Risk Factors; Role; Sampling; Socioeconomic Status; Testing; Time; Work; access restrictions; ambient air pollution; apolipoprotein E-4; brain health; brain volume; caucasian American; cognitive function; cognitive reserve; cognitive testing; dementia risk; deprivation; early life exposure; early-life disadvantage; experience; fine particles; innovation; low socioeconomic status; metropolitan; middle age; neighborhood disadvantage; neuropathology; novel; performance tests; polygenic risk score; prevent; processing speed; racial difference; racial disparity; residence; residential segregation; resilience; segregation; social; social disparities; social factors; socioeconomic disadvantage; socioeconomics; young adult

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.

项目总结/摘要 黑人阿尔茨海默病和相关痴呆症（ADRD）的发病率比黑人高40-100% 白色美国人。造成这种差异的一个关键原因可能包括居住在隔离的、社会上不利的环境中， 污染和污染的社区。现有的研究表明，社区社会经济剥夺与 脑容量减少，阿尔茨海默氏症的神经病理学和认知功能差， PM2.5可能导致神经退行性变。早期生活中的接触可能特别重要，因为 早期生活社区水平的不利因素和环境空气污染可能会破坏认知能力的积累， 储备，降低认知弹性，抑制社会轨迹。社区一级的社会因素和空气 污染往往同时发生;因此，全面了解这些因素如何独立运作， 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多基因风险评分-将有助于 ADRD的病因地位。本申请的总体目标是评估早期生活的影响， 社区层面的社会和环境因素对晚年ADRD的影响，以及这些因素在多大程度上影响老年ADRD。 在全国代表性样本中，对ADRD的种族差异表示敬意。核心假设是早期- 生活社区层面的社会因素和环境空气污染对晚期 生命脑健康和ADRD差异。 该项目利用了最近完成的1940年人口普查和国家卫生统计之间的数据联系。 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年之间的记忆评估，因此HRS包括长达23年的记忆纵向数据 分数和痴呆，子样本也有基因型信息。中心假设将在 在黑人和白色HRS参与者中有四个具体目标：（1）调查早期生活社区的影响- 水平的社会因素对晚年认知健康的影响;（2）检查早期生活环境空气污染暴露的影响， （3）评估早期社区水平社会因素的协同效应， 空气污染暴露对晚年认知健康的影响;（4）评估早期生活社区- 水平社会因素和暴露于环境空气污染改变了ADRD遗传风险对晚年认知能力的影响 积极健康。这项拟议中的研究是创新的，因为它评估了联合早期生活的社会和环境 社区水平的暴露，包括通过新的空气污染指标和20世纪30年代后期的红线，ADRD。的 预计拟议的工作将通过提供有关潜在战略的新的政策相关证据来推动该领域的发展， 预防ADRD和消除ADRD差异的战略。