Air pollution, Alzheimer's Disease and Related Outcomes

空气污染、阿尔茨海默病及相关结果

基本信息

  • 批准号:
    10251167
  • 负责人:
  • 金额:
    $ 63.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-30 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT The burden of Alzheimer’s disease and related dementia is substantial and growing. We have no disease- modifying treatments for most dementia sub-types, including Alzheimer’s disease dementia, and recent Alzheimer’s disease treatment trials have been disappointing. Thus, identifying ways to prevent or delay Alzheimer’s disease and related dementia may be our best option for reducing disease burden. Ambient air pollution exposure is a promising target for interventions to prevent or delay Alzheimer’s disease and related dementia. While the existing evidence linking ambient air pollution exposures to cognitive health and dementia is suggestive, it is insufficient to justify action. In order to recommend or develop effective interventions to reduce dementia burden through reductions in ambient air pollution exposure, we must first establish whether specific pollutants impact cognitive health, either overall or in susceptible subgroups. Thus, we propose to estimate associations between ambient exposure to U.S. EPA-regulated criteria air pollutants (Aim 1) and components of particulate matter air pollution (Aim 2) with incident Alzheimer’s disease and related dementia and related outcomes, overall and in potentially susceptible subgroups (Aim 3). While we will consider multiple air pollutants, our grant focuses on testing hypotheses that higher midlife and cumulative, mid- to late-life exposures to fine particulate matter (PM2.5), ozone (O3), and specific metals (Cd, V, Mn, Ni, V, Cr, and Pb) are associated with incident dementia and related outcomes. To complete these aims, we will use data from the Atherosclerosis Risk in Communities (ARIC) study, a unique cohort with incredible longitudinal data collected from midlife to late life. We will estimate exposure to air pollutants at each participant’s residential address throughout 25 years of follow-up, from midlife to late life, using an ensemble/data-fusing approach combining two chemical transport models (CMAQ, UCD/CTI), two emission inventories (NEI and EDGAR), available monitor data, and a local dispersion model, to maximize prediction accuracy. We will then evaluate whether midlife exposures or cumulative exposures from midlife to late life impact (i) cognitive decline from midlife to late life (n=14,040), (ii) incident dementia systematically assessed according to research criteria during follow- up (n=14,040), or (iii) neuroimaging evidence of dementia-related pathology in late life in a representative subset of ARIC participants (n=1,841). We will also conduct extensive sensitivity analyses to address residual confounding, selection bias, and measurement error/uncertainty due to use of estimated exposures. Throughout we will leverage an External Advisory Panel to ensure the best possible science and lay the groundwork for future collaboration. In order to recommend or develop effective interventions to reduce dementia burden through reductions in ambient air pollution exposure, we must first determine whether there is a link between specific pollutants and Alzheimer’s disease and related dementia, as well as what groups are most affected. The proposed work will provide evidence needed to answer to these questions.
项目总结/摘要 阿尔茨海默氏病和相关痴呆症的负担是巨大的,而且还在增长。我们没有疾病- 修改大多数痴呆症亚型的治疗方法,包括阿尔茨海默病痴呆症,以及最近的 阿尔茨海默病的治疗试验一直令人失望。因此,确定防止或推迟 阿尔茨海默病和相关的痴呆症可能是我们减少疾病负担的最佳选择。环境空气 污染暴露是预防或延迟阿尔茨海默病及相关疾病的干预措施的一个有希望的目标。 痴呆虽然现有的证据将环境空气污染暴露与认知健康和痴呆症联系起来, 是暗示性的,不足以证明行动是正当的。为了建议或制定有效的干预措施, 通过减少环境空气污染暴露来减少痴呆症负担,我们必须首先确定 特定的污染物影响认知健康,无论是整体还是易感亚组。因此,我们建议 估计环境暴露于美国EPA规定的标准空气污染物(目标1)和 颗粒物空气污染的组成部分(目标2)与阿尔茨海默病和相关痴呆症的发病率 和相关结果,总体和潜在易感亚组(目标3)。虽然我们会考虑多个 空气污染物,我们的赠款重点是测试假设,更高的中年和累积,中期到晚期的生活 细颗粒物(PM2.5)、臭氧(O3)和特定金属(Cd、V、Mn、Ni、V、Cr和Pb)的暴露量 与痴呆症的发生和相关结果有关。为了实现这些目标,我们将使用 社区动脉粥样硬化风险(ARIC)研究,一个独特的队列,收集了令人难以置信的纵向数据 从中年到晚年我们会估计每名参加者的居住地址所接触的空气污染物 在25年的随访中,从中年到晚年,使用整体/数据融合方法, 两个化学传输模型(CMAQ,UCD/CTI),两个排放清单(NEI和埃德加),可用 监测数据和本地分散模型,以最大限度地提高预测精度。我们将评估是否 中年暴露或从中年到晚年的累积暴露影响(i)从中年到晚年的认知能力下降 晚年(n= 14,040),(ii)在随访期间根据研究标准系统评估的痴呆事件- up(n= 14,040),或(iii)代表性患者晚年痴呆相关病理学的神经影像学证据 ARIC参与者的子集(n= 1,841)。我们还将进行广泛的敏感性分析, 混杂、选择偏倚和由于使用估计暴露而导致的测量误差/不确定性。 在整个过程中,我们将利用外部咨询小组,以确保最好的科学和奠定 为今后的合作打下基础。为了建议或制定有效的干预措施, 通过减少环境空气污染暴露,我们必须首先确定是否有 特定污染物与阿尔茨海默病和相关痴呆症之间的联系,以及哪些群体 最受影响。拟议的工作将提供回答这些问题所需的证据。

项目成果

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Melinda C Power其他文献

Melinda C Power的其他文献

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{{ truncateString('Melinda C Power', 18)}}的其他基金

Midlife statin use and late life cognition
中年他汀类药物的使用和晚年认知
  • 批准号:
    10523563
  • 财政年份:
    2022
  • 资助金额:
    $ 63.34万
  • 项目类别:
Air pollution, Alzheimer's Disease and Related Outcomes
空气污染、阿尔茨海默病及相关结果
  • 批准号:
    9789892
  • 财政年份:
    2018
  • 资助金额:
    $ 63.34万
  • 项目类别:
Air pollution, Alzheimer's Disease and Related Outcomes
空气污染、阿尔茨海默病及相关结果
  • 批准号:
    10020191
  • 财政年份:
    2018
  • 资助金额:
    $ 63.34万
  • 项目类别:
Environmental Determinants of Cognitive Function and Decline in Older Adults
老年人认知功能和衰退的环境决定因素
  • 批准号:
    8003255
  • 财政年份:
    2011
  • 资助金额:
    $ 63.34万
  • 项目类别:
Environmental Determinants of Cognitive Function and Decline in Older Adults
老年人认知功能和衰退的环境决定因素
  • 批准号:
    8232169
  • 财政年份:
    2011
  • 资助金额:
    $ 63.34万
  • 项目类别:

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