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Dementia Risk Does Not Increase With PPI Use

January 06, 2020

Proton-pump inhibitor (PPI) use does not increase dementia risk, according to findings of a new systematic review and meta-analysis.

“Long-term use of PPIs has been associated with a wide variety of potentially serious adverse effects, including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions,” the researchers wrote. “We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support.”

The review authors searched the MEDLINE, Embase, Web of Science, and Cochrane Library databases up to February 2019 for studies on the association between PPI use and dementia. Most of the studies that the authors identified and included were short-term, ranging from 5 to 10 years.

In all, the researchers analyzed data from 11 observational studies that comprised 642,949 participants—158,954 of whom were PPI users and 483,995 of whom were not.

Among the studies that had data summarized as adjusted hazard ratio (HR), the pooled HR was 1.10 (95% CI, 0.88-1.37) for all causes of dementia and 1.06 (95% CI, 0.72-1.55) for Alzheimer dementia only.

Among the studies that had data summarized as adjusted odds ratio (OR), the pooled OR was 1.03 (95% CI, 0.84-1.25) for all causes of dementia and 0.96 (95% CI, 0.82-1.11) for Alzheimer dementia only.

Using the Newcastle-Ottawa scale, the review authors determined that 10 studies were of high quality and 1 was of moderate quality. And by applying GRADE methodology, they found the quality of evidence for both outcomes to be very low.

“We found no evidence to support the proposed association between PPI use and an increased risk of dementia,” the researchers concluded. “PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.”

—Colleen Murphy


Khan MA, Yuan Y, Iqbal U, et al. No association linking short-term proton pump inhibitor use to dementia: systematic review and meta-analysis of observational studies [published online January 2, 2020]. Am J Gastroenterol. doi:10.14309/ajg.0000000000000500.

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