Potential Risk of Proton Pump Inhibitors for Parkinson’s Disease: a Nationwide Nested Case-control Study

Abstract The role of proton pump inhibitors (PPIs) in Parkinson's disease (PD) remains unclear. Thus, from the Korean National Health Insurance Services Database, we identified patients newly diagnosed with PD from January 2010 to December 2019 (N = 31,326) and healthy controls matched (1:4 ratio) by age, sex, body mass index, diabetes, hypertension, stroke, and dementia (N = 125,304). Cumulative defined daily doses (cDDDs) of PPIs were extracted from treatment claims. A conditional logistic regression analysis was used to evaluate the association. We excluded patients with PD diagnosed within a 1-year lag period after PPI exposure and applied 2- and 3-year lag periods for sensitivity analysis. PPI use was associated with an increased PD risk when all lag periods were applied. There was a significant positive dose-response relationship between the cDDDs of PPIs and PD development; moreover, PPI use increased the risk of PD in patients aged ≥ 50 years but not those aged < 50 years.