No Link Between PPIs and Dementia in New Study


A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.


  • Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.

  • 18,934 adults aged 65+ from the US and Australia without dementia at baseline.

  • 4667 (25%) PPI users and 368 (2%) H2RA users at baseline.

  • PPI and H2RA use, dementia incidence, and cognitive changes were tracked.


  • In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio [HR], 0.88) or cognitive impairment (HR, 1.00).

  • PPI use was not linked to changes in overall cognitive test scores over time (β -0.002).

  • No associations were found between H2RA use and cognitive endpoints.


“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.


The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online June 12 in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.


Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.


Mehta has disclosed no relevant conflicts of interest.

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