AbstractPurposeDue to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population.MethodsTwo surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use.ResultsNo association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: − 2.06 to − 0.16) in immediate recall, and 0.72 lower (95% CI: − 1.22 to − 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score.ConclusionsThe present study does not support a relationship between PPI use and brain aging.