Characteristics of the study population.

Proton pump inhibitor (PPI) use is a potential risk factor for neurodegenerative disease development; however, its role in Parkinson’s disease (PD) remains unclear. This study aimed to investigate the association between PPI use and PD risk. A total of 31,326 patients with newly diagnosed PD were matches by age, sex, body mass index, diabetes, and hypertension with 125,304 controls at a ratio of 1:4. The data were collected from the Korean National Health Insurance Services Database from January 2010 to December 2019. Cumulative defined daily doses of PPIs were extracted from treatment claims. We examined the association between PPI use and PD risk using conditional logistic regression. To prevent protopathic bias, we excluded patients diagnosed with PD within a 1-year lag period after PPI exposure. We applied 2- and 3-year lag periods for sensitivity analysis. PPI use was associated with an increased risk of PD when a 1-year lag period was applied between PPI exposure and PD development (adjusted odds ratio, 1.10; 95% confidence interval, 1.07–1.13). A significant positive dose-response relationship existed between the cumulative defined daily doses of PPIs and PD development (P<0.001). Similar results were obtained for the 2- or 3-year lag periods. The association did not vary based on gender. Older age, a higher Charlson Comorbidity Index score, no alcohol consumption, and a non-smoking status were associated with a significantly increased PD risk with PPI use. We observed an association between PPI use and PD risk, although long-term follow-up studies are necessary to verify this association.