Air Pollution and Alzheimer's Disease and Related Dementias: A National Study

痴呆症是一项重大的公共卫生挑战，造成巨大的经济和社会负担， 全球4700万人。阿尔茨海默氏病（AD）占痴呆病例的约三分之二，是老年痴呆症的主要病因。 这是美国第六大死亡原因，也是前十名中唯一无法治愈的诊断。 迫切需要通过以下方式支持阿尔茨海默病和相关痴呆（AD/ADRD）患者： 确定可能降低发病率的新的和可改变的风险因素。新出现的证据表明， 污染-特别是细颗粒物（PM2.5）-在AD/ADRD发病机制中起重要作用。 然而，人们对不同空气污染物（PM2.5、NO2、臭氧）的相对贡献知之甚少， PM2.5成分。为了促进污染控制工作的目标，国家科学院（NAS） 和世界卫生组织（WHO）高度重视确定哪些空气污染物和/或 PM2.5中哪些成分最具毒性此外，新出现的流行病学证据中的一个主要差距是， 关于空气污染和AD/ADRD发病率的一个重要因素是，许多以前的研究依赖于住院治疗， 发病率的衡量标准。然而，住院并不是AD/ADRD诊断和初始治疗的典型过程。 相反，如果患者确实发生了这种情况，则住院治疗发生在疾病的更晚期阶段 并且通常用于治疗疾病的并发症。因此，住院记录不能准确反映 发病率，从而低估了病例数。因此，我们提出了一项研究，将利用 高分辨率环境暴露数据和医疗保险索赔（包括医生访问）的海量数据集 大多数AD/ADRD诊断将发生的地方），以更好地了解 空气污染对美国老年人AD/ADRD发病率的影响，并确定潜在的脆弱亚群， 最终目标是制定环境政策。我们将（1）生成并验证一个全面的，高- 2000-2021年美国本土分辨率、多物种、空气污染数据集，包括标准空气 污染物（PM2.5质量、NO2和臭氧）、PM2.5组分（包括微量金属）以及气溶胶水 和可能影响金属溶解的细颗粒pH值;（2）估计标准污染物的慢性效应 （PM2.5，NO2和臭氧）对AD/ADRD风险的影响，使用全国医疗保险慢性疾病仓库 (CCW)数据库，其中包括医疗保险住院和门诊索赔，医生访问，熟练的护理设施， 在约1亿医疗保险受益人中，AD/ADRD的家庭医疗保健索赔;（3）评估 PM2.5组分的贡献和气溶胶水/pH值对AD/ADRD风险的潜在影响修改， 全国医疗保险队列;（4）通过校正暴露测量值进行敏感性分析 错误和结果错误分类。我们提出的研究将填补流行病学的主要知识空白， 环境暴露和AD/ADRD发病率，并为针对特定来源的法规政策提供信息 并促进可采取的措施，以预防或减轻空气污染造成的AD健康负担。

Dementia is a major public health challenge with substantial economic and social burden, affecting more than 47 million people worldwide. Alzheimer's disease (AD) constitutes about two-thirds of dementia cases and is the sixth leading cause of death in the United States, and the only diagnosis among the top 10 that cannot be cured. There is a pressing need to support Alzheimer's disease and related dementias (AD/ADRD) patients by identifying novel and modifiable risk factors that may reduce morbidity. Emerging evidence suggests that air pollution – in particular fine particulate matter (PM2.5) – plays an important role in AD/ADRD pathogenesis. However, little is known about the relative contributions of different air pollutants (PM2.5, NO2, ozone), nor about PM2.5 components. To facilitate the targeting of pollution control efforts, the National Academy of Sciences (NAS) and the World Health Organization (WHO) have placed a high priority on determining which air pollutants and/or which components of PM2.5 are most toxic. In addition, one major gap in the emerging epidemiologic evidence on air pollution and AD/ADRD morbidity is that many previous studies have relied on hospitalizations as the measure of morbidity. Yet, hospitalization is not the typical course for AD/ADRD diagnosis and initial treatment. Instead, if it does occur for patients, hospitalization happens during the more advanced stages of the disease and usually for treating complications of the disease. Thus, hospitalization records do not accurately reflect disease incidence, and thus underestimate case numbers. Therefore, we propose a study that will leverage the massive datasets of high-resolution environmental exposure data and Medicare claims (including doctor visits where most AD/ADRD diagnoses would occur) across the contiguous US to better understand the influence of air pollution on AD/ADRD morbidity among US elderly, and identify potential vulnerable subpopulations, with the ultimate goal of informing environmental policy. We will (1) generate and validate a comprehensive, high- resolution, multiple-species, air pollution dataset across the contiguous US for 2000-2021, including criteria air pollutants (PM2.5 mass, NO2, and ozone), PM2.5 components (including trace metals), as well as aerosol water and fine particle pH that may influence metal dissolution; (2) estimate the chronic effects of criteria pollutants (PM2.5, NO2, and ozone) on AD/ADRD risks using the nationwide Medicare Chronic Conditions Warehouse (CCW) database, which includes Medicare inpatient and outpatient claims, doctor visits, skilled nursing facility, and home health-care claims for AD/ADRD among ~100 million Medicare beneficiaries; (3) assess the relative contributions of PM2.5 components and potential effect modification by aerosol water/pH on AD/ADRD risks using the nationwide Medicare cohort; and (4) conduct sensitivity analyses by correcting for exposure measurement error and outcome misclassification. Our proposed research will fill major knowledge gaps in the epidemiology of environmental exposures and AD/ADRD morbidity, and inform policy for targeted source-specific regulations and facilitate actionable measures that can prevent or mitigate the AD health burden due to air pollution.