title: Effect of pioglitazone medication on the incidence of dementia.
abstract: OBJECTIVE
  Peroxisome proliferator activated receptor γ-activating drugs show various salutary effects in preclinical models of neurodegenerative disease. The decade-long clinical usage of these drugs as antidiabetics now allows for evaluation of patient-oriented data sources.
  
  
  METHODS
  Using observational data from 2004-2010, we analyzed the association of pioglitazone and incidence of dementia in a prospective cohort study of 145,928 subjects aged ≥60 years who, at baseline, were free of dementia and insulin-dependent diabetes mellitus. We distinguished between nondiabetics, diabetics without pioglitazone, diabetics with prescriptions of <8 calendar quarters of pioglitazone, and diabetics with ≥8 quarters. Cox proportional hazard models explored the relative risk (RR) of dementia incidence dependent on pioglitazone use adjusted for sex, age, use of rosiglitazone or metformin, and cardiovascular comorbidities.
  
  
  RESULTS
  Long-term use of pioglitazone was associated with a lower dementia incidence. Relative to nondiabetics, the cumulative long-term use of pioglitazone reduced the dementia risk by 47% (RR = 0.53, p = 0.029). If diabetes patients used pioglitazone <8 quarters, the dementia risk was comparable to those of nondiabetics (RR = 1.16, p = 0.317), and diabetes patients without a pioglitazone treatment had a 23% increase in dementia risk (RR = 1.23, p < 0.001). We did not find evidence for age effects, nor for selection into pioglitazone treatment due to obesity.
  
  
  CONCLUSIONS
  These findings indicate that pioglitazone treatment is associated with a reduced dementia risk in initially non-insulin-dependent diabetes mellitus patients. Prospective clinical trials are needed to evaluate a possible neuroprotective effect in these patients in an ageing population.
authors.affiliation: German Center for Neurodegenerative Diseases, Bonn, Germany.|Clinical Neurosciences, Department of Neurology, University of Bonn, Bonn, Germany.|Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
authors.affiliation: German Center for Neurodegenerative Diseases, Bonn, Germany.|Rostock Center for the Study of Demographic Change, Rostock, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fink
authors.affiliation: German Center for Neurodegenerative Diseases, Bonn, Germany.|Rostock Center for the Study of Demographic Change, Rostock, Germany.|Institute for Sociology and Demography, University of Rostock, Rostock, Germany.|Max Planck Institute for Demographic Research, Rostock, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Doblhammer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D003704:Dementia / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D011446:Prospective Studies; D065840:Protective Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone