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

Yerim Kim; Seung In Seo; Kyung Joo Lee; Jinseob Kim; Jong Jin Yoo; Won-Woo Seo; Hyung Seok Lee; Woon Geon Shin

doi:10.1177/17562864221135700

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

Ther Adv Neurol Disord. 2022 Nov 8:15:17562864221135700. doi: 10.1177/17562864221135700. eCollection 2022.

Authors

Yerim Kim¹, Seung In Seo^{2

3}, Kyung Joo Lee⁴, Jinseob Kim⁵, Jong Jin Yoo⁶, Won-Woo Seo⁷, Hyung Seok Lee⁸, Woon Geon Shin^{9

3}

Affiliations

¹ Department of Neurology, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.
² Division of Gastroenterology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.
³ Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea.
⁴ University Industry Foundation, Hallym University, Chuncheon, South Korea.
⁵ Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea.
⁶ Division of Rheumatology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.
⁷ Division of Cardiology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.
⁸ Division of Nephrology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, South Korea.
⁹ Division of Gastroenterology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, 150, Seongan-ro, Gangdong-gu, Seoul 05355, South Korea.

Abstract

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 (H₂RA) 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 H₂RA 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 H₂RA 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.

Keywords: Alzheimer disease; Common Data Model; H2 receptor antagonist; dementia; proton-pump inhibitors.