Extreme weather-related events and environmental exposures in the risk for Alzheimer's disease and related dementias

项目总结 2018全国老龄AD研究院峰会推介 将“环境对推进疾病预防的影响”作为治疗和预防疾病的关键战略计划 到2025年预防阿尔茨海默病和相关痴呆症(ADRD)。暴露在极端环境中 与天气有关的事件、空气污染和环境污染物无处不在，但很少有 了解他们与ADRD的关系，特别是在多元化的老年人口中。这个 拟议的研究通过将不同的住宅历史联系起来，解决了文献中的关键空白 来自3个正在进行的NIH资助的队列研究(Kaiser Healthy Aging)的超过3379人的样本 和多样化的生活经历(Khandle，n=1712，平均年龄76.2岁，71%非白人)，研究 非裔美国人的健康老龄化(STAR，n=764，平均年龄68.4%，100%非白人)及其以后的生活 90(洛杉矶90，n=903，平均年龄92.7岁，72%非白人))到新收集的环境数据 暴露，并将产生新的细粒度、全面的环境生命周期措施 暴露将被用来检查他们与ADRD的关联。所有研究都在进行 协调神经认知评估、临床检查和神经成像，收集关于 生命周期风险因素，并与健康数据(20世纪60年代至90年代)和电子病历相关联 (1996年至今)。收集了七个时间点的居住历史(出生当期)，并将 地理编码并链接到历史暴露数据。这项研究的总体目标是调查 暴露于与极端天气有关的事件、空气污染和有毒环境污染物 不同老龄化人群的认知功能、ADRD和神经影像生物标志物。在一种独特的 以及前所未有的机会，全面评估晚年生活中的环境暴露 大脑结果，这项研究将在3379个不同的北加州中解决以下问题 居民：(1)测试暴露于极端天气相关事件(Extreme)之间的关联 高温、干旱、野火)对神经成像标记物、认知功能下降和ADRD的影响；(2)确定 暴露于环境颗粒物空气污染(细颗粒物和超细颗粒物)之间的关系 物质(PM2.5，PM0.1)对神经成像标记物、认知衰退和ADRD的影响；以及(3)评估 接触有毒环境污染物(铅、汞)与健康的关系 神经影像标记物、认知功能减退和ADRD。利用累积性和时间依赖性 暴露于这些环境因素将照亮暴露于这些因素的生命周期 环境因素对大脑的健康老化尤为重要。这项研究的发现有 有可能发现ADRD和认知能力下降的新风险因素，并提供ADRD的目标 这将改善所有种族/民族的人的健康大脑老化。

PROJECT SUMMARY The 2018 National Institute on Aging AD Research Summit recommendation of “Understanding the Impact of the Environment to Advance Disease Prevention” as a key strategic plan to treat and prevent Alzheimer's Disease and related dementias (ADRD) by 2025. Exposure to extreme weather-related events, air pollution, and environmental contaminants are pervasive, yet little is known about their relationships with ADRD, especially among a diverse older population. The proposed study addresses critical gaps in the literature by linking residential history on a diverse sample of over 3,379 individuals from 3 ongoing NIH-funded cohort studies (Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE, n=1712, mean age 76.2, 71% non- White), the Study of Healthy Aging in African-Americans (STAR, n=764, mean age 68.4, 100% non-White) andLife After 90 (LA 90, n=903, mean age 92.7, 72% non-White)) to newly collected data on environmental exposures and will generate new granular, comprehensive, lifecourse measures of environmental exposures that will be used to examine their association with ADRD. All studies conduct harmonized neurocognitive assessments, clinical exams and neuroimaging, collect information on lifecourse risk factors, and are linked to health data (1960s-1990s) and electronic medical records (1996-present). Residential history at seven time points is collected (birth-current), and will be geocoded and linked to historic exposure data. The overall objective of this studyis to investigate exposure to extreme weather-related events, air pollution, and toxic environmental contaminants on cognitive function, ADRD, and neuroimaging biomarker in diverse aging populations. In a unique and unprecedented opportunity to comprehensively evaluate environmental exposures on late-life brainoutcomes, this study will address the following among 3,379 diverse Northern California residents: (1) Test the associations between exposure to extreme weather-related events (extreme heat, drought, wildfire) on neuroimaging markers, cognitive decline, and ADRD; (2) Determine the associations between exposure to ambient particulate air pollution (fine and ultrafine particulate matter (PM2.5, PM0.1)) on neuroimaging markers, cognitive decline, and ADRD; and (3) Assess the relationships between exposure to toxic environmental contaminants (lead, mercury) on neuroimaging markers, cognitive decline, and ADRD. Leveraging cumulative and time-dependent exposure to these environmental factors will illuminate lifecourse period in which exposureto these environmental factors is especially salient to healthy brain aging. Findings from this study have the potential to uncover new risk factors for ADRD and cognitive decline, and provide targets of ADRD interventionthat would improve healthy brain aging for people of all racial/ethnic groups.