Proton Pump Inhibitors and the Risk of Dementia

Proton pump inhibitors (PPIs) are the most prescribed gastric acid suppressant drugs; the category includes omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. In 2015, a study suggested that PPI use was associated with an increased risk of dementia. An early meta-analysis confirmed this concern, but the findings were inconsistent in subsequent meta-analyses. Also problematic is that these meta-analyses used questionable approaches, and their findings were characterized by very high heterogeneity. Notably, the high heterogeneity appeared to be driven by large studies with widely different outcomes. Nonetheless, one finding stands out in the body of research examined: older subjects who initiated and continued PPIs (implying chronic use) were at a significantly increased risk of dementia and mild cognitive impairment. Although there are causal and non-causal pathways that associate PPI use with dementia, for reasons that are explained in this article, a cause-effect relationship cannot at present be presumed; so, PPI use is best considered to be a marker of future dementia risk. However, because chronic use of PPIs has been associated with many adverse medical outcomes (eg, disturbances of the gut microbiome, orthopedic complications), and because some PPIs are associated with pharmacokinetic drug interactions (mainly inhibition of CYP2C19), it would be wise to limit the use of PPIs to the shortest duration necessary and to deprescribe PPIs when there does not appear to be need for their continuation.