July 20, 2017
2 min read

Another study finds no link between PPIs, dementia

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Andrew T. Chan, MD, MPH
Andrew T. Chan

Researchers report they found “no convincing evidence” of an association between the use of proton pump inhibitors and risk for dementia in a new study, which a press release from the AGA said, “puts these claims to rest.”

This confirms the same findings of a recent longitudinal observational study, and differs from the findings of a pharmacoepidemiologic study using a large German health insurance database.

“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,” Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, said in the press release. “Our new research should provide some reassurance to individuals who require these highly effective medications for long-term treatment.”

Chan and colleagues evaluated associations between use of PPIs and H2 receptor antagonists (H2RAs) and the results of cognitive function tests using prospectively collected data on 13,864 women who participated in the Nurses’ Health Study II. All participants completed a self-administered battery of computerized neuropsychological tests that measured psychomotor speed and attention, learning and working memory, and overall cognition (mean age at testing, 61 years; range, 50-70 years).

The investigators saw a slight link between the duration of PPI use and poorer psychomotor speed and attention scores: compared with those who never used PPIs, those who took them for 9 to 14 years showed an average score difference of –0.06 (95% CI; –0.11 to 0; P for trend = .03). However, the strength of the association diminished after they controlled for use of H2RAs.

Further, they saw an association between duration of H2RA use and poorer cognitive scores in those who did not regularly use PPIs. The strongest of these associations affected learning and working memory scores, with an average difference of –0.2 (95% CI; –0.32 to –0.08; P for trend < .001) in those who used H2RAs for 9 to 14 years compared with those who never used them.

“After adjusting for multiple potential confounding factors, including H2RA use, we did not observe a convincing association between use of PPIs and cognitive function in middle-aged and older women,” Chan and colleagues concluded, adding that “our findings for H2RA use should be interpreted with some caution considering that this was not our primary hypothesis.”

In response to growing concerns about the health risks of PPIs, the AGA recently issued 10 best practice recommendations for long-term PPI use, and argued that the benefits of PPIs likely outweigh the risks when prescribed appropriately. Similarly, the AGA responded to a recent study linking PPI use to a higher risk for death by posting an interpretation of the data on its website and a guide for effective communication about the findings with patients. – by Adam Leitenberger


AGA. A Guide to Conversations About the Latest PPI Research Results. July 6, 2017. http://www.gastro.org/news_items/a-guide-to-conversations-about-the-latest-ppi-research-results. Accessed July 7, 2017.

Disclosures: Chan reports he has served as a consultant for Bayer Healthcare, Pfizer, and Aralez Pharmaceuticals. Another researcher (Khalili) reports he receives consulting fees from AbbVie, Samsung Bioepis and Takeda Pharmaceuticals.