Regular proton pump inhibitor use and incident dementia: population-based cohort study
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 indivi...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-022-02478-y |
| _version_ | 1798004318331207680 |
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| author | Peidong Zhang Zhihao Li Peiliang Chen Ao Zhang Yu Zeng Xiru Zhang Qingmei Huang Dan Liu Songtao Qi Chen Mao |
| author_facet | Peidong Zhang Zhihao Li Peiliang Chen Ao Zhang Yu Zeng Xiru Zhang Qingmei Huang Dan Liu Songtao Qi Chen Mao |
| author_sort | Peidong Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T12:21:35Z |
| format | Article |
| id | doaj.art-87a2aaa057314bd4b04e1752e1d33648 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-11T12:21:35Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-87a2aaa057314bd4b04e1752e1d336482022-12-22T04:24:05ZengBMCBMC Medicine1741-70152022-09-0120111110.1186/s12916-022-02478-yRegular proton pump inhibitor use and incident dementia: population-based cohort studyPeidong Zhang0Zhihao Li1Peiliang Chen2Ao Zhang3Yu Zeng4Xiru Zhang5Qingmei Huang6Dan Liu7Songtao Qi8Chen Mao9Department of Epidemiology, School of Public Health, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityState Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and TechnologyGuangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityDepartment of Neurosurgery, Nanfang Hospital, Southern Medical UniversityDepartment of Epidemiology, School of Public Health, Southern Medical UniversityAbstract 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.https://doi.org/10.1186/s12916-022-02478-yProton pump inhibitorsDementiaAlzheimer’s diseaseAPOEAmyloid-β |
| spellingShingle | Peidong Zhang Zhihao Li Peiliang Chen Ao Zhang Yu Zeng Xiru Zhang Qingmei Huang Dan Liu Songtao Qi Chen Mao Regular proton pump inhibitor use and incident dementia: population-based cohort study BMC Medicine Proton pump inhibitors Dementia Alzheimer’s disease APOE Amyloid-β |
| title | Regular proton pump inhibitor use and incident dementia: population-based cohort study |
| title_full | Regular proton pump inhibitor use and incident dementia: population-based cohort study |
| title_fullStr | Regular proton pump inhibitor use and incident dementia: population-based cohort study |
| title_full_unstemmed | Regular proton pump inhibitor use and incident dementia: population-based cohort study |
| title_short | Regular proton pump inhibitor use and incident dementia: population-based cohort study |
| title_sort | regular proton pump inhibitor use and incident dementia population based cohort study |
| topic | Proton pump inhibitors Dementia Alzheimer’s disease APOE Amyloid-β |
| url | https://doi.org/10.1186/s12916-022-02478-y |
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