title: Dementia, cognitive impairment and proton pump inhibitor therapy: A systematic review.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) are among the most widely used medications worldwide. Dementia is an increasingly common cause of disability in older populations. Recent studies have suggested an increased risk of cognitive impairment and dementia diagnosis among people who consume PPIs. This systematic review explores dementia, cognitive impairment, and the use of PPIs.
  
  
  METHODS
  Systematic searches were conducted in the databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PSYCinfo, Scopus, Web of Science, and ClinicalTrials.gov for articles published from inception to June 30, 2016. Primary outcomes of interest were the use of PPIs and diagnosis of dementia or acute cognitive impairment. Studies conducted on people aged less than 18 years old were excluded. All study designs were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from included studies.
  
  
  RESULTS
  The systematic search strategy and screening process yielded 11 studies for inclusion in the systematic review. Four studies explored PPI use and dementia, and seven studies explored PPI use and acute cognitive impairment. Three of the four studies exploring dementia identified a positive association with PPI use. A positive association was also observed in the majority of studies exploring acute cognitive impairment.
  
  
  CONCLUSIONS
  Based on the current published literature, this systematic review has identified that the reported association between PPI use and dementia is limited by methodological issues and conflicting results. Further longitudinal studies with robust bias limitation are required to explore the use of PPIs and dementia or acute cognitive impairment, and to ascertain the existence of any causal relationships.
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Riley
authors.initials: R
authors.lastname: Batchelor
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.|Research Department of Practice and Policy, University College London School of Pharmacy, London, UK.
authors.forename: Julia Fiona-Maree
authors.initials: JF
authors.lastname: Gilmartin
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Kemp
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hopper
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
mesh_terms: D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000453:epidemiology; D016206:Databases, Bibliographic; D003704:Dementia / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012306:Risk
chemical_list: D054328:Proton Pump Inhibitors
keywords: gastric secretion; gastroenterology; gastroesophagus reflux disease (GERD)