Abstract
BACKGROUND: Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. OBJECTIVES: This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and nitrogen dioxide (NO2). METHODS: We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient PM2.5 and NO2 in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 (n = 163). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: NO2 exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in NO2, adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per 4.8 ppb increment in NO2 was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of NO2 with PD risk was limited to women in urban, rural, and small town areas and women with ≥ 50th percentile ADI but not among women from suburban areas or areas with < 50th percentile ADI. In contrast, PM2.5 exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (HRinterquartile-range = 2.49, 95% CI: 1.20, 5.14) but not in other census regions. DISCUSSION: In this nationwide cohort of US women, higher level exposure to ambient NO2 is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.