Effect of pioglitazone medication on the incidence of dementia

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ObjectivePeroxisome 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.MethodsUsing 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.ResultsLong-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.InterpretationThese 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. Ann Neurol 2015;78:284–294

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