November 2023
Proton pump inhibitors and dementia risk

Longer use of proton pump inhibitors increased dementia risk in a community-based cohort.

Proton pump inhibitors (PPIs), used to treat gastro-oesophageal reflux disease and peptic ulcers, may increase dementia risk, although research has shown mixed results. In this study, researchers determined whether PPI use was associated with incident dementia, assessing data from an epidemiological cohort of four US communities that began Visit 1 assessments from 1987 to 1989. This analysis included participants who were free of dementia at Visit 5 of the larger study (2011 to 2013). PPI use was determined by visual inventory and study phone call reports of medications. Cumulative PPI exposure was based on years of PPI use before Visit 5. Incident dementia was based on in-person examinations, a telephone cognitive screener, hospital discharge codes or death records.

Among 5712 participants in the analysis (mean age 75 years, 22% Black, 58% female), 10% developed dementia after a follow up of six years. Cumulative PPI use ranged from 112 days to 20 years. There was no significant difference in dementia risk between those not using PPIs and PPI users overall, after adjustment for demographics, apolipoprotein E ε4 status, body mass index, vitamin B12 medication use and use of anticholinergic or histamine-2 receptor antagonist medications. However, those who used PPIs for more than 4.4 years had a 33% higher dementia risk than those who did not use PPIs in fully adjusted models.

Comment: Cumulative use of PPIs may increase dementia risk, although the mechanisms behind this association are not well established. Including more comprehensive neuropsychological evaluations, cognitive biomarkers and possibly even gut microbiome testing in future prospective studies may provide further insight into this potential connection.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Jennifer Rose V. Molano, MD, Associate Professor, Department of Neurology and Rehabilitation Medicine, The University of Cincinnati, Ohio, USA.

Northuis C, et al. Cumulative use of proton pump inhibitors and risk of dementia: the Atherosclerosis Risk in Communities Study. Neurology 2023 Aug 9; e-pub (https://doi. org/10.1212/WNL.0000000000207747).

This summary is taken from the following Journal Watch title: Neurology.