Wang · European journal of clinical pharmacology 2022 · systematic review and meta-analysis · n=17 studies (1,251,562 participants)

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

Cited 12 times in the scientific literature.

Level 3 - non-randomized controlled study

Meta-analysis of observational studies reporting adjusted hazard ratios.

PubMed 34811582 · doi:10.1007/s00228-021-03248-0 · record verified 2026-08-28

What was done

A systematic review and random-effects meta-analysis was conducted across PubMed, EMBASE, and Cochrane Library databases through April 2021. Eligible studies reported adjusted hazard ratios (HR) and 95% confidence intervals (CI) evaluating the association between proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and dementia risk.

What was found

Across 17 included studies comprising 1,251,562 participants, PPI use was not associated with dementia risk compared to non-use (HR = 0.98, 95% CI: 0.85–1.13). Subgroup analyses by publication year, study location, mean age, PPI duration, and female proportion also showed no association. Similarly, H2RA use was not significantly associated with dementia risk (pooled HR = 1.20, 95% CI: 0.98–1.47).

Why it matters

These findings provide reassurance against prior observational concerns suggesting that common acid-suppressing medications increase the risk of cognitive decline and dementia.

Limits

The analysis relies entirely on observational studies subject to residual confounding, protopathic bias, and exposure misclassification. The abstract does not specify study-level heterogeneity metrics (e.g., I-squared) or the specific types of dementia evaluated.

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