Association Between Proton Pump Inhibitor Use and Cognitive Function in Women

Background & Aims Studies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim. Methods We used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed a self-administered computerized neuropsychological test battery. Multivariable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition. Results We observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9−14 years vs never users, −0.06; 95% confidence interval, −0.11 to 0.00; P_trend =.03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory (mean score difference for H2RA users of 9−14 years vs never users, −0.20; 95% confidence interval, −0.32 to −0.08; P_trend <.001). Conclusions In an analysis of data from the Nurses’ Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.