No association between acid suppressant use and risk of dementia: an updated meta-analysis

Findings from large observational studies on whether the use of acid suppressants increases the risk of dementia have been inconsistent. Since proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are the most commonly used acid suppressants in clinical practice, we performed a meta-analysis to examine the influence of PPI and H2RA on the risk of dementia.

A systematic search was performed on the PubMed, EMBASE, and Cochrane Library databases to identify studies published up to April, 2021. Studies that reported adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the associations of interest were included. Data in the included studies were pooled using the random-effects model for meta-analysis. Statistical analysis was performed using Stata version 12.0 software.

Seventeen studies involving 1,251,562 participants were included. It was found that PPI users were not likely to develop dementia compared with those not taking PPI (HR = 0.98, 95% CI: 0.85-1.13). Subgroup analysis based on publication year, location, mean age, duration of PPI use, and female proportion also revealed no association between PPI use and dementia risk. Similarly, H2RA use was not associated with the risk of dementia, as indicated by the pooled HR of 1.20 (95% CI: 0.98-1.47).

Results of this meta-analysis suggest that PPI and H2RA do not increase the risk of dementia. These results may be used to inform the clinical application of acid suppressants. However, further randomized controlled trials are needed to confirm the present conclusions.