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

• Published in: BMC medicine Vol. 20; no. 1; pp. 271 - 11
• Main Authors: Zhang, Peidong, Li, Zhihao, Chen, Peiliang, Zhang, Ao, Zeng, Yu, Zhang, Xiru, Huang, Qingmei, Liu, Dan, Qi, Songtao, Mao, Chen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01-09-2022; BioMed Central; BMC
• Subjects: Adult; Aged; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid-β; APOE; Apolipoprotein E; Apolipoprotein E4 - drug effects; Cohort analysis; Cohort Studies; Comorbidity; Complications and side effects; Dementia; Dementia disorders; Dementia, Vascular - epidemiology; Development and progression; Female; Gastroesophageal reflux; Genotype & phenotype; Genotypes; Health risk assessment; Heterozygotes; Humans; Inhibitors; Metabolism; Middle Aged; Neurodegenerative diseases; Observational studies; Population; Population studies; Population-based studies; Proton pump inhibitors; Proton Pump Inhibitors - adverse effects; Protons; Risk Factors; Statistical models; Vascular dementia; United Kingdom; United Kingdom > UK; Proton pump inhibitors; APOE; Amyloid-β; Alzheimer’s disease; Dementia
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-022-02478-y

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.
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.
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.
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.