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，具有巨大的经济和社会负担，影响到超过 全球有4700万人。阿尔茨海默病(AD)约占痴呆症病例的三分之二，是 美国第六大死因，也是前十名中唯一无法治愈的诊断。 迫切需要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修改的风险因素。新出现的证据表明，空气 污染--尤其是细颗粒物(PM2.5)--在AD/ADRD的发病机制中起着重要作用。 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，也不知道 PM2.5组件。为了促进污染控制工作的针对性，美国国家科学院(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的哪些成分毒性最强。此外，新出现的流行病学证据中的一个主要差距 关于空气污染和AD/ADRD发病率的研究表明，以前的许多研究都依赖于住院治疗，因为 发病率的衡量标准。然而，住院并不是AD/ADRD诊断和初步治疗的典型过程。 相反，如果确实发生在患者身上，住院治疗发生在疾病的更晚期。 通常用于治疗疾病的并发症。因此，住院记录不能准确地反映 疾病发病率，因此低估了病例数量。因此，我们建议进行一项研究，以利用 高分辨率环境暴露数据和医疗保险索赔(包括就诊)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，并确定潜在的易受伤害亚群，与 告知环境政策的最终目标。我们将(1)生成并验证全面、高度- 分辨率，多物种，2000-2021年连续美国的空气污染数据集，包括空气标准 污染物(PM2.5质量、NO2和臭氧)、PM2.5成分(包括痕量金属)以及气溶胶水 以及可能影响金属溶解的细颗粒物pH值；(2)估计标准污染物的慢性影响 (PM2.5、NO2和臭氧)对AD/ADRD的风险使用全国医疗保险慢性病仓库 (CCW)数据库，其中包括医疗保险住院和门诊索赔、医生就诊、熟练护理设施、 以及约1亿医疗保险受益人中AD/ADRD的家庭保健索赔；(3)评估亲属 PM2.5组分的贡献和气溶胶水/pH对AD/ADRD风险的潜在影响 全国医疗保险队列；以及(4)通过校正暴露测量来进行敏感性分析 错误和结果错误分类。我们提议的研究将填补流行病学方面的主要知识空白 环境暴露和AD/ADRD发病率，并为针对特定来源的法规提供政策信息 并促进采取可行措施，预防或减轻由于空气污染造成的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.