Proton Pump Inhibitor Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis

Introduction Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer’s disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies. Objective The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD). Methods We conducted a case–control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration. Results As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80–0.97) or VaD (aOR 1.18, 95% CI 1.04–1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87–1.02) or VaD (aOR 0.99, 95% CI 0.89–1.10). Conclusion In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.