Use of gastric acid-suppressive agents increases the risk of dementia in patients with upper gastrointestinal disease: A populationbased retrospective cohort study

Background Prescriptions for gastric acid-suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). Methods We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan's Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid-suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid-suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. Results The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid- suppressive agents compared with patients with UGID without gastric acid-suppressive agents was 1.470 (95% confidence interval [CI] 1.267-1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377-2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098-1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022-2.075], p < 0.05). Conclusions Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid-suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.