title: Effects of pioglitazone on the incidence of dementia in patients with diabetes.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists exert neuroprotective effects in the brain. Therefore, in this population-based cohort study, we investigated the effects of pioglitazone, a PPAR-γ agonist, on the risk of dementia.
  
  
  METHODS
  By using claims data from Taiwan's National Health Insurance Research Database, we included 6401 patients with diabetes who were treated with pioglitazone and 12,802 age- and sex-matched patients with diabetes who were never treated with pioglitazone from 2004 to 2009 and who were free of dementia at baseline.
  
  
  RESULTS
  In total, 113 (1.8%) and 323 (2.5%) patients in the pioglitazone-treated and comparison cohorts, respectively, developed dementia during the 5-year follow-up. The risk of dementia decreased by 23% in the pioglitazone-treated cohort compared with that in the comparison cohort after adjustment for age, sex, hypertension, and stroke (adjusted hazard ratio [HR], 0.77; 95% confidence interval [CI]=0.62-0.96). In addition, the adjusted HRs (95% CIs) for dementia were 0.50 (0.34-0.75, P=.001) in high-cumulative dose users, 0.53 (0.36-0.77, P<.001) in long-term users, and 0.66 (0.49-0.90, P=.009) in high-mean daily dose users.
  
  
  CONCLUSIONS
  Pioglitazone is a time- and dose-dependent protective factor against dementia in patients with diabetes. The risk of dementia is lower in long-term and high-dose pioglitazone users than in never users of pioglitazone.
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ping-Song
authors.initials: PS
authors.lastname: Chou
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Bo-Lin
authors.initials: BL
authors.lastname: Ho
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of and Master's Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: endlessyhy@gmail.com.
authors.forename: Yuan-Han
authors.initials: YH
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003704:Dementia / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000453:epidemiology / Q000517:prevention & control; D000077205:Pioglitazone; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Dementia; Diabetes mellitus; National health insurance research database; Peroxisome proliferator-activated receptor gamma; Pioglitazone