Associations between proton pump inhibitors and Alzheimer’s disease: a nested case–control study using a Korean nationwide health screening cohort

BACKGROUND: Safety concerns against the use of proton pump inhibitors (PPIs) based on the risk of dementia, especially Alzheimer’s disease (AD), remain controversial. Here, we investigated the likelihood of AD depending on previous PPI exposure, use duration, and PPI generation. METHODS: This nested case–control study comprised 17,225 AD patients who were 1:4 matched with 68,900 controls for age, sex, income, and region of residence from Korean National Health Insurance Service-Health Screening Cohort data between 2002 and 2015 using propensity-score matching method. Conditional and unconditional logistic regression analyses were used to evaluate the effects of previous PPI use on AD adjusting for multiple covariates. RESULTS: Prior PPI use increased likelihood for AD in current and past PPI users (adjusted odds ratio 1.36 [95% confidence interval (CI) = 1.26–1.46] and 1.11 [95% CI = 1.04–1.18], respectively). Participants with either < 30 days, 30–90 days, or > 90 days of PPI prescription showed higher odds for AD (1.13 [95% CI = 1.07–1.19]; 1.18 [95% CI = 1.10–1.27]; 1.26 [95% CI = 1.16–1.36], respectively). Participants with either 1st-generation or 2nd-generation PPIs demonstrated higher incidences of AD in those with < 30 days (1.14 [95% CI = 1.07–1.22] and 1.13 [95% CI = 1.05–1.22], respectively), 30–90 days (1.19 [95% CI = 1.09–1.30] and 1.17 [95% CI = 1.05–1.29], respectively), or > 90 days (1.18 [95% CI = 1.07–1.30] and 1.27 [95% CI = 1.14–1.43], respectively) of prescription. CONCLUSIONS: Prior PPI use, regardless of current or past exposure, duration of use, or use of 1st- or 2nd-generation PPIs, may increase likelihood of AD, providing supportive evidence of previous pharmacoepidemiologic studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-01032-5.