Ambient air pollutants as determinants of disparities in Alzheimer's disease and co-existing morbidity

摘要 环境空气污染物与阿尔茨海默病(AD)、与痴呆症相关的高风险相关 (ADRD)和认知障碍；然而，空气污染水平的变化如何影响地理 AD/ADRD风险的差异以及这些贡献背后的机制仍不清楚。结果是 我们的父母赠款显示，先前存在的动脉高血压、糖尿病、脑血管疾病和慢性 肾脏疾病对AD/ADRD风险的种族差异有很大影响。这些疾病依次是 与接触空气污染物，包括颗粒物(PM2.5)有关。建议的一年制 该项目是对我们父母资助的目标3的补充。它将定量地评估变异的贡献 通过直接(暴露于PM2.5)和间接的方式，将PM2.5水平与AD/ADRD风险和存活率的地理差异联系起来 (通过对共存疾病的影响)机制，并确定特定于年龄、性别和种族/民族的 易受PM2.5影响的人群。本项目的目标是对PM2.5进行量化 与AD风险较高相关的并存疾病对地区差异的影响和作用 AD/ADRD发生率和存活率。中发展的因果调解和分解分析方法 我们的父母赠款将用于评估PM2.5对AD/ADRD风险和患者生存期差异的贡献 并确定共存疾病在造成这种差异中所起的作用。传统的经验主义和 将使用回归方法、基于倾向分数的方法和其他因果分析方法 量化PM2.5和AD/ADRD之间的关联，并确定相关的因果机制。这个 推广的Oaxaca-Blinder方法用于事件间隔时间数据和二元因果中介分析 调解人和活动时间结果将被用来解释观察到的地理差异 预测者。预期结果将提供有关环境PM2.5对 美国老年人AD/ADRD风险和存活率的地理差异 高度脆弱的人口群体。这项研究将评估1)PM水平是否小幅下降(可能不会 对个人水平有明显影响)可以大幅降低人口层面的AD/ADRD风险；2)如果 低于世界卫生组织(WHO)标准的环境空气污染物水平有助于 AD/ADRD风险增加；3)通过PM2.5，哪些共存疾病对AD/ADRD风险贡献最大- 相关途径；以及4)改善特定地理区域的空气质量如何减少地理 AD/ADRD之间的差异。拟议的研究与NIH/NIA的任务和战略方向有关 2020-2025年关于了解与老龄化有关的健康差距并制定改善战略的研究 不同人群中老年人的健康(目标F)。

Abstract Ambient air contaminants have been associated with higher risk of Alzheimer's disease (AD), related dementia (ADRD), and cognitive impairment; however, how variations in air pollution levels contribute to geographic disparities in AD/ADRD risk and what mechanisms underlay these contributions remains unclear. The results of our parent grant showed that pre-existing arterial hypertension, diabetes mellitus, cerebrovascular, and chronic kidney diseases have a strong impact on racial disparities in AD/ADRD risk. These diseases in turn are associated with exposure to air contaminants, including particulate matter (PM2.5). The proposed one-year project is supplemental to Aim 3 of our parent grant. It will quantitatively evaluate the contributions of variations in PM2.5 levels to geographic disparities in AD/ADRD risk and survival via direct (exposure to PM2.5) and indirect (through the effects on co-existing diseases) mechanisms and identify age-, sex-, and race/ethnicity-specific populations at higher vulnerability to PM2.5 effects. The Aim of this project focuses on quantification of PM2.5 impacts and the role of co-existing diseases that are associated with higher AD risk on geographic disparities in AD/ADRD incidence and survival. The methods of causal mediation and decomposition analyses developed in our parent grant will be used to evaluate contributions of PM2.5 to disparities in AD/ADRD risk and patient survival and to identify the role co-existing diseases play in generating in such disparities. Traditional empiric and regression approaches, propensity-score based methods, and other methods of causal analysis will be used for quantifying the association between PM2.5 and AD/ADRD and to identify associated causal mechanisms. The Oaxaca-Blinder approach generalized for use of time-to-event data and the causal mediation analyses for binary mediators and time-to-event outcomes will be applied to explain the observed geographic disparities in terms of predictors. The expected outcome will provide quantitative information on the contribution of ambient PM2.5 to geographic disparities in AD/ADRD risk and survival in the U.S. population of older adults with specific focus on highly vulnerable population groups. This study will assess 1) if a small reduction of PM levels (that may not have visible impact on an individual level) can substantially reduce AD/ADRD risk on a population level; 2) if the levels of ambient air contaminants that are below the World Health Organization (WHO) standards contribute to increased risks of AD/ADRD; 3) which co-existing diseases contribute most to AD/ADRD risk through a PM2.5 - related pathway; and 4) how improving the air quality in specific geographic areas can reduce geographic disparities in AD/ADRD. The proposed research is relevant to the NIH/NIA mission and Strategic Directions for Research 2020-2025 on understanding health disparities related to aging and developing strategies to improve the health of older adults in diverse populations (Goal F).