PPI use not associated with dementia, study concludes

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PPIThere is no convincing evidence to support previous suggestions that proton-pump inhibitor (PPI) use increases dementia risk, concludes a Harvard analysis of the Nurses’ Health Study II.

These findings are based on an analysis 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.

PPIs are widely prescribed for the treatment of acid-related upper gastrointestinal disorders, such as gastroesophageal reflux disease (GERD). While PPIs are known to effectively treat these conditions, they have received negative publicity in recent years as research has associated PPIs with several adverse outcomes.

“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,” said study author Dr Andrew T Chan, an expert of the American Gastroenterological Association from 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.”

This research directly responds to a 2016 pharmaco-epidemiologic analysis conducted using a large German health insurance database, which identified an association between dementia and long-term PPI use; however, these findings could not illustrate that PPIs caused dementia. Despite the attention this article received at the time, AGA expressed its concerns on this research at the time of publication.

Three important reminders for patients taking PPIs: talk to your doctor before making any changes to your medication. You have been prescribed PPIs for a reason, to treat a diagnosed medical condition. You and your doctor can discuss the reason for your prescription, the dose and the timeframe for treatment; consider life-style modifications that may reduce or eliminate the need for PPIs for long-term use. These may include weight loss, avoiding tobacco or a change in your eating patterns. Your doctor can help you determine the changes that are right for you; keep in touch with your doctor. Research continues to be done on PPI use. While the latest research and headlines on PPIs may seem scary, current research still recommends that patients who have a diagnosed condition that is helped by PPIs should stay on them, as benefits can outweigh risks.

Background & Aims: Studies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim.
Methods: We used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed a self-administered computerized neuropsychological test battery. Multi-variable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition.
Results: We observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9–14 yrs vs never users, –0.06; 95% CI, –0.11 to 0.00; Ptrend = .03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals 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 (mean score difference for H2RA users of 9–14 years vs never users, –0.20; 95% CI, –0.32 to –0.08; Ptrend < .001).
Conclusions: In an analysis of data from the Nurses’ Health Study II, we did not observe a convincing association between PPI use and cognitive function. 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.

Paul Lochhead, Kaitlin Hagan, Amit D Joshi, Hamed Khalili, Long H Nguyen, Francine Grodstein, Andrew T Chan

American Gastroenterological Society material
Gastroenterology abstract

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