Long-term use of proton-pump inhibitor on Alzheimer’s disease: a real-world distributed network analysis of six observational Korean databases using a Common Data Model

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.