Proton pump inhibitor use and risk of dementia in a population-based cohort study.

Understanding the effect of long-term medication exposure in middle-aged to older adults is crucial for dementia prevention. Proton pump inhibitors (PPIs), widely used for gastrointestinal conditions, have shown inconsistent associations with dementia risk. We conducted a retrospective cohort study using the Taiwan Adult Preventive Health Services and National Health Insurance databases. The study included 2,444,999 adults aged ≥ 40 years without baseline dementia. Incident dementia and cumulative PPI use, calculated as cumulative defined daily doses, were tracked. Multivariate Cox proportional hazards models estimated hazard ratios (HRs), adjusting for age, sex, BMI, lifestyle factors, and comorbidities like hypertension and diabetes. During follow-up, 137,126 participants (5.6%) developed dementia (mean age: 72.7 years; 58.6% females). PPI use was associated with an increased dementia risk in a dose-response manner (HR 1.66; 95% CI, 1.64-1.69 for the high-exposure category). The strongest associations were observed in the younger cohort: individuals aged < 65 years with high-exposure exhibited a significantly higher risk (HR 1.97; 95% CI, 1.89-2.06) compared to older groups. PPI use is associated with an elevated, dose-dependent risk of all-cause dementia in this observational cohort. While this association attenuates with advancing age, potential causal mechanisms remain to be fully elucidated.