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

空气污染与阿尔茨海默病及相关痴呆症：一项全国研究

基本信息

批准号：
10301914
负责人：
Liuhua Shi
金额：
$ 73.22万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10301914
关键词：
Acidity Address Aerosols Affect Air Pollutants Air Pollution Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Ammonia Bayesian Method Biological Biological Availability Caring Cause of Death Chemicals Chronic Coupled Data Data Set Databases Dementia Diagnosis Disease Economics Elderly Environmental Epidemiology Environmental Exposure Environmental Policy Epidemiology Event Exposure to Gases Goals Health Health protection Home Care Services Hospitalization Impaired cognition Incidence Individual Inpatients Knowledge Learning Link Liquid substance Long-Term Effects Longitudinal cohort Measurement Measures Medicare Medicare claim Metals Modeling Modification Morbidity - disease rate Nitrogen Dioxide Noise Outcome Outpatients Oxidative Stress Ozone Particulate Matter Pathogenesis Pathway interactions Patients Phase Play Policies Pollution Positioning Attribute Public Health Publishing Race Records Regulation Reporting Research Resolution Risk Factors Role Sensitivity and Specificity Skilled Nursing Facilities Source Statistical Methods Survival Analysis Thermodynamics Time Toxic effect Toxicology Trace metal Uncertainty United States United States National Academy of Sciences Update Visit Water Work World Health Organization ambient air pollution base beneficiary cognitive function cohort data warehouse dementia risk fine particles flexibility high risk human old age (65+)machine learning method modifiable risk neuroinflammation novel pollutant prevent response sex social systemic inflammatory response

项目摘要

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.

痴呆症是一项重大的公共卫生挑战，带来巨大的经济和社会负担，影响超过全球有 4700 万人患有阿尔茨海默病 (AD)，约占痴呆症病例的三分之二。美国第六大死因，也是前十名中唯一无法治愈的诊断。迫切需要通过以下方式支持阿尔茨海默氏病和相关痴呆症 (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空气。污染，尤其是细颗粒物 (PM2.5)，在 AD/ADRD 发病机制中发挥着重要作用。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，也不清楚 PM2.5 成分。为了促进污染控制工作的针对性，美国国家科学院 (NAS) 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空白。关于空气污染和 AD/ADRD 发病率的一个重要问题是，之前的许多研究都依赖住院治疗作为然而，住院治疗并不是 AD/ADRD 诊断和初始治疗的典型过程。相反，如果患者确实发生这种情况，住院治疗会发生在疾病的更晚期阶段通常用于治疗疾病的并发症，因此住院记录不能准确反映。疾病发病率，从而低估了病例数因此，我们提出了一项研究，该研究将利用高分辨率环境暴露数据和医疗保险索赔（包括医生就诊）的海量数据集在美国本土，大多数 AD/ADRD 诊断发生的地方），以更好地了解空气污染对美国老年人 AD/ADRD 发病率的影响，并确定潜在的弱势群体，我们将 (1) 生成并验证全面的、高水平的环境政策。 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成分（包括微量金属）以及气溶胶水以及可能影响金属溶解的细颗粒pH值；（2）估算污染物的慢性影响标准；使用全国医疗保险慢性病仓库（PM2.5、NO2 和臭氧）了解 AD/ADRD 风险 (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、约 1 亿医疗保险受益人的 AD/ADRD 家庭医疗保健索赔 (3) 评估亲属； PM2.5 成分的贡献以及气溶胶水/pH 对 AD/ADRD 风险的潜在影响修改全国医疗保险队列；(4) 通过校正暴露测量来进行敏感性分析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，并为有针对性的特定源法规政策提供信息促进采取可行措施，预防或减轻空气污染造成的 AD 健康负担。