Boston—In response to studies finding associations between proton-pump inhibitor (PPI) use and dementia, a new review offers evidence to the contrary.

The report in Gastroenterology, the official journal of the American Gastroenterological Association (AGA), argues that there is no compelling evidence to support the suggestion
that PPI use increases dementia risk.

To reach those conclusions, the study, led by researchers from Massachusetts General Hospital and Harvard Medical School, analyzed the medical history of 13,864 participants from the Nurses’ Health Study II who completed testing on cognitive function, which is key predictor of the risk of dementia later in life.

“One of the most common questions gastroenterologists receive from their patients is whether PPIs are safe to use, based on the troubling headlines linking PPIs to everything from hip fracture, to dementia, to death,” pointed out study author Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston. “Our new research should provide some reassurance to individuals who require these highly effective medications for long-term treatment.”

Among the studies refuted by the research is a 2016 pharmacoepidemiologic analysis conducted using a large German health insurance database, which identified an association between dementia and long-term PPI use. Even at the time of publication, AGA expressed concerns because the results did not actually prove that PPIs were the cause of the dementia.

The recent study also examined associations for H2 receptor antagonists (H2RAs) as a secondary aim. The nurses participating in the trial completed a self-administered computerized neuropsychological test battery. Study authors examined possible associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition.

Results indicate a modest association between duration of PPI use and scores for psychomotor speed and attention—mean score difference of -0.06 for 9 to 14 years of PPI use versus never-users. After controlling for H2RA use, however, the magnitude of this score difference was diminished. The study found that, among those who did not regularly use PPIs, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory, with a mean score difference for H2RA users of 9 to 14 years versus never-users of -0.20.

“In an analysis of data from the Nurses’ Health Study II, we did not observe a convincing association between PPI use and cognitive function,” study authors conclude. “Our data do not support the suggestion that PPI use increases dementia risk. Since our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.”

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