Air Pollutants and Risk of Parkinson's Disease among Women in the Sister Study

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 $\le 2.5\mu m$ (${\mathrm{PM}}_{2.5}$) and nitrogen dioxide (${\mathrm{NO}}_2$).

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 ${\mathrm{PM}}_{2.5}$ and ${\mathrm{NO}}_2$ 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: ${\mathrm{NO}}_2$ 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 ${\mathrm{NO}}_2$, 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 $4.8\text{ppb}$ increment in ${\mathrm{NO}}_2$ 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 ${\mathrm{NO}}_2$ with PD risk was limited to women in urban, rural, and small town areas and women with $\ge 50\text{th}$ percentile ADI but not among women from suburban areas or areas with $<50\text{th}$ percentile ADI. In contrast, ${\mathrm{PM}}_{2.5}$ exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (${\text{HR}}_{\text{interquartile}\text{-range}}=2.49$, 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 ${\mathrm{NO}}_2$ 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.