A249 PROTON PUMP INHIBITOR USE AND RISK OF DEMENTIA: AN UMBRELLA REVIEW OF SYSTEMATIC REVIEWS AND META-ANALYSES

TL;DR

This umbrella review finds inconsistent evidence linking long-term proton pump inhibitor use to dementia, with only one high-quality study showing a significant association.

Contribution

The study synthesizes multiple systematic reviews and meta-analyses to clarify the inconsistent evidence on PPI use and dementia risk.

Findings

Only one high-quality systematic review significantly associated PPI use with dementia.

Subgroup analyses showed increased dementia risk in older patients and with long-term PPI use.

Most reviews found no significant link between PPI use and Alzheimer’s disease.

Abstract

Clinical studies about the association between long term PPI use and dementia have been inconsistent, with systematic reviews and meta-analyses (SR/MA) reaching disparate conclusions.

This umbrella review of SR/MA attempts to clarify the current understanding of any possible association linking PPI use to dementia.

We searched Embase, Medline, CENTRAL and ISI Web of Science for fully published SR/MA in English up to June 2024 using controlled vocabulary and text words ((1) proton pump and (2) dementia (dementia and mild cognitive impairment, Alzheimer disease)). SR/MA methodological quality was scored using the AMSTAR-2 tool.

Eleven SR/MA published (May 2016 - February 2023) described 21 studies (one randomized trial). Only one high-quality SR/MA significantly associated PPI use with dementia. None of six SR/MA investigating PPI use and Alzheimer’s disease showed a significant association. Significant associations with dementia in subgroup analyses were found in one SR/MA each for older patients (age > 65 years) (HR=1.39 (1.17;1.65)), long term PPI use (> 5 years) (HR=1.28 (1.12; 1.46)), short term PPI use (< 5 years) (RR=1.62 (1.40–1.86)), when only considering higher quality studies (RR=1.54 (1.12; 2.13)), and amongst European populations (HR=1.46 (1.23–1.73)). Two SR/MA found an association when only assessing prospective cohort studies (RR=1.36 (1.19; 1.55)), (RR=1.44 (1.36; 1.52)).

Most SR/MA suggest no link between PPI use and dementia. Only properly designed, adequately powered randomized trials can rule out a small but significant association possibly linking PPI use to dementia.

N = study number in SR/MA, HR = hazards ratio, RR = relative risk, OR = odds ratio, NA = Not applicable

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