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

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];  = 1701), and with faster memory decline in AD over time (rate ratio = 0.76 [0.64-0.92];  = 628), but not with progression from normal cognition to MCI (HR = 0.94 [0.71-1.24];  = 2784).

Discussion: Compared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre-existing cognitive impairment.