Causal association between long-term exposure to air pollution and incident Parkinson’s disease

Epidemiological evidence for long-term air pollution exposure and Parkinson's disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006-2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1,822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD. In recent years, it has been proposed that exposure to ambient air pollution may play a part in the development of Parkinson's disease (PD). However, epidemiological evidence regarding air pollution and PD is controversial, and analysis of causality is lacking. Based on a prospective cohort study, we investigated the associations between long-term exposure to PM2.5 and O3 and the incidence of PD using multiple causal modeling approaches. We found robust associations between PM2.5 exposure and PD, suggesting that there could be a causal relationship between long-term exposure to air pollution, particularly PM2.5, and incident PD. Our findings suggest that air pollution mitigation could be a preventive measure against PD."