Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan

PLoS One. 2017 Feb 15;12(2):e0171006. doi: 10.1371/journal.pone.0171006. eCollection 2017.

Abstract

Introduction: 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Asian People
  • Databases, Factual*
  • Dementia / chemically induced*
  • Dementia / epidemiology*
  • Depression / drug therapy
  • Depression / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipidemias / drug therapy
  • Hyperlipidemias / epidemiology
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / epidemiology
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Taiwan / epidemiology

Substances

  • Proton Pump Inhibitors

Grants and funding

This study was supported by grants from the Ministry of Science and Technology (MOST103-2314-B-037-004-MY3), Research Center for Environmental Medicine, Kaohsiung Medical University (KMU-TP104A34), and Kaohsiung Medical University Hospital (KMUH105-5R64). The authors are thankful for the assistance provided by the Statistical Analysis Laboratory, Department of Medical Research, Kaohsiung Municipal Ta-Tung Hospital. None of these organizations had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.