| Summary: | Background: Dementia has a crucial impact on the quality of life of elderly patients and their caregivers. Proton-pump inhibitors (PPIs) are the most frequently prescribed treatment, but they have been shown to be associated with dementia. The data are inconsistent, however. Objective: To investigate the association between PPIs use and Alzheimer’s disease (AD) or all-cause dementia in six observational Korean databases using a Common Data Model (CDM) and to perform a distributed network analysis. Methods: Subjects aged over 18 years between 1 January 2004 and 31 December 2020. Among 7,293,565 subjects from 6 cohorts, 41,670 patients met the eligibility criteria. A total of 2206 patients who were included in both cohorts or with a history of dementia were excluded. After propensity matching, 5699 propensity-matched pairs between the PPIs and histamine-2 receptor antagonist (H 2 RA) users were included in this study. The primary outcome was the incidence of AD at least 365 days after drug exposure. The secondary outcome was the incidence of all-cause dementia at least 365 days after drug exposure. Results: In the 1:1 propensity score matching, the risk of AD or all-cause dementia was not significantly different between the PPIs and H 2 RA groups in all six databases. In the distributed network analysis, the long-term PPI users (⩾365 days) were unassociated with AD [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.68–1.23; I 2 = 0%] and all-cause dementia (HR =1.04, 95% CI = 0.82–1.31; I 2 = 0%) compared with H 2 RA users. Conclusion: In the distributed network analysis of six Korean hospital databases using Observational Medical Outcomes Partnership (OMOP)-CDM data, the long-term use of PPI was not associated with a statistically significantly increased risk of AD or all-cause dementia. Therefore, we suggest that physicians should not avoid these medications because of concern about dementia risk.
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