Gastric acid suppressants and cognitive decline in people with or without cognitive impairment

Abstract

Introduction: Studies suggest associations between proton pump inhibitors (PPIs) and dementia risk; however, many neither considered histamine-2 receptor antagonists (H2RAs) nor baseline cognitive status. Methods: Participants (National Alzheimer's Coordinating Center Database; 2005–2021) using a PPI or H2RA were compared. Covariate-adjusted Cox regression was used to estimate hazard ratios (HR) for progression from normal cognition to mild cognitive impairment (MCI), and from MCI to dementia over 5 years. In a propensity-score–matched subsample of mild–moderate Alzheimer's disease (AD), mixed-effects negative binomial regression was used to estimate decline in delayed recall memory. Results: Compared to PPI, H2RA use was associated with earlier progression from MCI to dementia (HR = 1.40 [1.09–1.81]; n = 1701), and with faster memory decline in AD over time (rate ratio = 0.76 [0.64–0.92]; n = 628), but not with progression from normal cognition to MCI (HR = 0.94 [0.71–1.24]; n = 2784). Discussion: Compared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre-existing cognitive impairment.