4.8 Article

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

期刊

BMC MEDICINE
卷 20, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12916-022-02478-y

关键词

Proton pump inhibitors; Dementia; Alzheimer's disease; APOE; Amyloid-beta

资金

  1. National Natural Science Foundation of China [82103931, 82003443]
  2. Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019)
  3. Guangdong Basic and Applied Basic Research Foundation [2022A1515012085, 2021A1515110230]
  4. Science and Technology Project in Guangzhou [202002030255, 201902020017]
  5. China Postdoctoral Science Foundation [2021M701633]
  6. Young Elite Scientists Sponsorship Program by CAST [2019QNRC001]

向作者/读者索取更多资源

The use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE epsilon 4 heterozygotes, according to the findings of this large population-based cohort study.
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 epsilon 4 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 epsilon 4 heterozygotes.

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