Effect of pioglitazone medication on the incidence of dementia

Ann Neurol. 2015 Aug;78(2):284-94. doi: 10.1002/ana.24439. Epub 2015 Jun 30.


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.

Interpretation: 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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Dementia / epidemiology*
  • Diabetes Mellitus / drug therapy*
  • Female
  • Germany / epidemiology
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Insulin / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone
  • Proportional Hazards Models
  • Prospective Studies
  • Protective Factors
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*


  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin
  • Pioglitazone