title: Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan.
abstract: BACKGROUND
  Concerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia.
  
  
  OBJECTIVE
  This study aimed to examine this association in an Asian population.
  
  
  METHODS
  Patients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan's National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use.
  
  
  RESULTS
  We analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non-PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR [aHR] 1.22; 95% confidence interval: 1.05-1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 [1.91-3.89]), hyperlipidemia (aHR 1.81 [1.38-2.38]), ischemic heart disease (aHR 1.55 [1.12-2.14]), and hypertension (aHR 1.54 [1.21-1.95]).
  
  
  CONCLUSIONS
  An increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted.
authors.affiliation: Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Tai
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Otorhinolaryngology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Chien
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.|Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.|Division of Endocrinology and Metabolism, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.
authors.forename: Kun-Der
authors.initials: KD
authors.lastname: Lin
authors.affiliation: Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Bo-Lin
authors.initials: BL
authors.lastname: Ho
authors.affiliation: Management Office, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.|Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Yang-Pei
authors.identifier: http://orcid.org/0000-0002-1021-2643
authors.initials: YP
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D016208:Databases, Factual; D003704:Dementia / Q000139:chemically induced* / Q000453:epidemiology*; D003863:Depression / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000453:epidemiology; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000453:epidemiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D054328:Proton Pump Inhibitors