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Short-term PPI use does not increase risk of dementia

Stephen Padilla
09 Jun 2020

No association appears to exist between use of proton pump inhibitors (PPIs) in the short term and an increased risk of dementia, according to the results of a systematic review and meta-analysis.

“As for all drugs, PPIs should be given in the lowest effective dose, and their use should be restricted to patients with valid indications,” the investigators said. “If PPI use in an elderly patient is for an appropriate indication, there is no justification to stop it because of concerns about dementia.”

The databases of Medline, Embase, ISI Web of Science, and Cochrane were searched for studies examining the link between PPI use and dementia up to February 2019. Eleven observational studies comprising a total of 642,949 patients (64 percent women) were included in the meta-analysis, and most of these were short-term, ranging from 5 to 10 years. Of the patients included, 158,954 were PPI users and 483,995 were nonusers.

The DerSimonian and Laird random-effects model was used to pool studies reporting summary results as hazard ratio (HR) or odds ratio (OR) for the meta-analyses. The investigators also assessed the methodological quality of individual studies using the Newcastle-Ottawa scale and rated the overall quality of evidence based on the GRADE approach.

For studies summarizing data as adjusted HR, the pooled HR was 1.10 (95 percent confidence interval [CI], 0.88–1.37) for all causes of dementia and 1.06 (95 percent CI, 0.72–1.55) for Alzheimer’s dementia only. For those summarizing data as adjusted OR, the pooled ORs were 1.03 (95 percent CI, 0.84–1.25) and 0.96 (95 percent CI, 0.82–1.11), respectively. [Am J Gastroenterol 2020;115:671-678]

Assessment with the Newcastle-Ottawa scale revealed 10 studies of high quality and one of moderate quality. Using the GRADE methodology, quality of evidence for both outcomes was found to be very low.

“Our results are consistent with a large case-control study and certain population cohort studies that used robust methods for detection of dementia in the form of regular cognitive screening, standardized dementia evaluations, neuropsychological evaluations, and/or computed tomography/MRI scans and are based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition,” the investigators said. [J Am Geriatr Soc 2017;65:1969-1974; J Am Geriatr Soc 2018;66:247-253; Am J Gastroenterol 2017;112:1802-1808]

Additionally, a recent randomized controlled trial comparing treatment with pantoprazole or placebo in a group of patients on rivaroxaban, aspirin, or both reported no association between PPI use and adverse outcomes, including a diagnosis of dementia. [Gastroenterology 2019;157:682-691]

Of note, a web-based survey of US patients on PPI therapy revealed that many patients were opting to discontinue treatment without medical advice. [Am J Gastroenterol 2019;114:244-249]

“Our important negative finding—of no proven association between relatively short-term PPI use and the development of dementia—should be relevant for clinicians caring for elderly patients and can hopefully reassure some patients and their family members who may have concerns about this proposed association,” the investigators said.

PPIs are one of the most commonly used medicines worldwide and are usually given to elderly patients. [BMJ 2008;336:2-3]

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