A national cohort study (2000\u20132018) of long-term air pollution exposure and incident dementia in older adults in the United States

Liuhua Shi,Rodney J Weber,Sindana D Ilango,Joel Schwartz,Yuhan Zhang,Pengfei Liu,Howard H Chang,Robert H Lyles,Haomin Li,Kyle Steenland,Thomas Wingo,Weeberb J Requia

doi:10.1038/s41467-021-27049-2

Abstract

Air pollution may increase risk of Alzheimer’s disease and related dementias (ADRD) in the U.S., but the extent of this relationship is unclear. Here, we constructed two national U.S. population-based cohorts of those aged ≥65 from the Medicare Chronic Conditions Warehouse (2000–2018), combined with high-resolution air pollution datasets, to investigate the association of long-term exposure to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with dementia and AD incidence, respectively. We identified ~2.0 million incident dementia cases (N = 12,233,371; dementia cohort) and ~0.8 million incident AD cases (N = 12,456,447; AD cohort). Per interquartile range (IQR) increase in the 5-year average PM2.5 (3.2 µg/m3), NO2 (11.6 ppb), and warm-season O3 (5.3 ppb) over the past 5 years prior to diagnosis, the hazard ratios (HRs) were 1.060 (95% confidence interval [CI]: 1.054, 1.066), 1.019 (95% CI: 1.012, 1.026), and 0.990 (95% CI: 0.987, 0.993) for incident dementias, and 1.078 (95% CI: 1.070, 1.086), 1.031 (95% CI: 1.023, 1.039), and 0.982 (95%CI: 0.977, 0.986) for incident AD, respectively, for the three pollutants. For both outcomes, concentration-response relationships for PM2.5 and NO2 were approximately linear. Our study suggests that exposures to PM2.5 and NO2 are associated with incidence of dementia and AD.

Highlights

Dementia is a major public health issue, affecting >47 million people worldwide[1]
We found elevated hazard ratios (HRs) for both dementia and Alzheimer’s disease (AD) in relation to PM2.5, and less markedly to NO2, while HRs for warm-season O3 were not elevated
We did this study in a large US cohort (12 million), with national coverage, and including non-urban areas. For both PM2.5 and NO2, we found a larger effect on AD compared to dementia, which may reflect the fact that dementia includes a wide range of diseases with distinct etiologies, some of which may be unrelated to air pollution, while AD is a subset of dementia and a single disease, for which we found a stronger association

Summary

Introduction

Dementia is a major public health issue, affecting >47 million people worldwide[1]. Alzheimer’s disease (AD) contributes to about two-thirds of dementia cases and is the sixth leading cause of death in the United States[2]. There have been several longitudinal studies since these reviews, with the majority finding positive associations between air pollutants and either dementia or AD6–14. Neuropathologic changes are known to occur many years prior to the diagnosis[15], and the relevant time window in which air pollution might increase the risk of dementia or AD is unclear. To address these knowledge gaps in studying ADRD incidence in the US, here we constructed a national, population-based cohort study from Medicare data to investigate the impact of long-term exposure to PM2.5, NO2, and warm-season (May to October) O3 on dementia and AD incidence. We assigned air pollution exposure to subjects based on resident ZIP code, and calculated time-varying 5-year lagged moving averages for each follow-up year

Methods

Results

Conclusion