Over the last 20 years, there have been multiple retrospective studies which have shown associations between the use of proton pump inhibitors (PPIs) and a wide constellation of serious medical complications. However, detecting an association between a drug and a complication does not necessarily indicate that the drug was indeed responsible.
The evidence supporting the assertion that PPIs cause cognitive decline is among the most tenuous of all the PPI/complication associations. The initial reports linking PPI use to dementia emerged in 2016 based on the results of a German retrospective analysis, which showed an association between PPIs and having a health care contact coded as dementia. However, this study had numerous methodological flaws, including the investigators not using a validated definition for dementia and not being able to control for conditions that may be more common in both PPI users and persons with dementia. In addition, there is little reason to believe that PPIs, based on their mechanism of action, should have any negative effect on cognitive function. Nevertheless, this paper was extensively cited in the lay press, and likely led to the inappropriate discontinuation of PPI therapy among persons with ongoing indications, or in the failure to start PPI therapy in persons who would have derived benefit.
This well-done study by Wod et al, which shows no significant association between PPI use and decreased cognition and cognitive decline will, I hope, serve to allay any misplaced concerns that may exist among clinicians and patients about PPI use in this population. This paper has notable strengths, most importantly having access to results of a direct, unbiased assessment of changes in cognitive function over time and accurate assessment of PPI exposure. Short of performing a controlled, prospective trial, we are unlikely to see better evidence indicating a lack of a causal relationship between PPI use and changes in cognitive function. This provides assurance that patients with indications for PPI use can continue to use them.
Laura E. Targownik, MD, MSHS, FRCPC, is section head, section of gastroenterology, University of Manitoba, Winnipeg, Canada; Gastroenterology and Endoscopy Site Lead, Health Sciences Centre, Winnipeg; associate director, University of Manitoba Inflammatory Bowel Disease Research Centre; associate professor, department of internal medicine, section of gastroenterology, University of Manitoba. She has no conflicts of interest.
