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Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Vascular Dementia | Research article

Regular proton pump inhibitor use and incident dementia: population-based cohort study

Authors: Peidong Zhang, Zhihao Li, Peiliang Chen, Ao Zhang, Yu Zeng, Xiru Zhang, Qingmei Huang, Dan Liu, Songtao Qi, Chen Mao

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

To examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes.

Methods

Based on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model.

Results

During 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07–1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02–1.49) for incident AD, and 1.32 (95% CI, 1.05–1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22–1.75) and 1.68 (95% CI, 1.36–2.07), especially for individuals aged 65 years and older.

Conclusions

The finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.
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Metadata
Title
Regular proton pump inhibitor use and incident dementia: population-based cohort study
Authors
Peidong Zhang
Zhihao Li
Peiliang Chen
Ao Zhang
Yu Zeng
Xiru Zhang
Qingmei Huang
Dan Liu
Songtao Qi
Chen Mao
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02478-y

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