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Background

Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia. However, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonists (H2RA) use with dementia and cognitive decline.

Methods

We conducted a post-hoc analysis of Aspirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use was determined according to review of medications during annual in-person study visits. Incident dementia was defined according to DSM-IV criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models.

Results

Baseline PPI use versus non-use was not associated with incident dementia (multivariable HR 0.88, 95% CI 0.72-1.08); CIND (multivariable HR 1.00, 95% CI 0.92-1.09); or with changes in overall cognitive test scores over time (multivariable B -0.002, SE 0.01, P=0.85). Similarly, no associations were observed between H2RA use and all cognitive endpoints.

Conclusions

In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

You can read an interview with the senior study author here, and about the clinical implications of the study here.