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Proton pump inhibitors (PPIs) represent a widely used class of medications for the treatment of acid-related gastrointestinal conditions worldwide. Prior studies have suggested that PPI use is associated with an increased risk of dementia, which has increased public concern about the possible adverse effects of PPIs. However, the interpretation of this finding is limited due to several design limitations in previous studies, including failure to account for confounders and incomplete assessment of medication use.

Mehta et al. conducted a prospective cohort study, based on the post-hoc analysis of Aspirin in Reducing Events in the Elderly (ASPREE), a randomized multicenter trial of aspirin in the U.S. and Australia, to examine the association of PPI and histamine-2 receptor antagonists (H2RA) use with dementia and cognitive decline, which was recently published in .

A total of 18,934 community-based adults ages 65 and older were evaluated at baseline and at subsequent visits over more than 6 years of follow-up, which included serial, in-depth cognitive testing, and review of medications. Among the enrolled patients, 4,667 users of PPI and 368 users of H2RA were identified. Baseline PPI use was not associated with risk for dementia (HR 0.88, 95% CI 0.72-1.08), cognitive impairment without dementia (HR 1.00, 95% CI 0.92-1.09), or changes in overall cognitive test scores over time (B -0.002, SE 0.01, P=0.85).

Moreover, no significant association was observed between H2RA use and the aforementioned cognitive endpoints. All multivariable analyses were adjusted for age, sex, years of education, country, race/ethnicity, smoking status, alcohol consumption, body mass index, family history of dementia, chronic kidney disease, type 2 diabetes, hypertension, depression score, baseline cognition, the randomized trial intervention (aspirin or placebo), and the concomitant medications.

Clinically, this recent study suggests that baseline, new, and ongoing PPI and HR2A use are not associated with an increased risk of dementia, cognitive impairment, or overall cognitive decline. The findings offer additional and updated reassurance that the long-term use of PPIs among older adults is likely not harmful.

Laura S. Chiu, MD, MPH, is an assistant professor of medicine at Boston University School of Medicine.

You can read an interview with the senior study author here, and the abstract of the study here.