Activation of the peroxisome proliferator activated receptor gamma (PPAR?) has been found to improve behavioural deficits and neuropathological changes in mouse models of Alzheimer’s disease by suppressing neuroinflammation, increasing microglial Aß clearance and direct modulation of beta-secretase-1 promotor activity. Pioglitazone is a PPAR? agonist, widely used for the treatment of non-insulin dependent type 2 diabetes. Based on the above preclinical data, researchers hypothesized that sustained medication with pioglitazone would reduce the risk of dementia.
Using routine data of the German largest public sickness fund of the years 2004 until 2010 researchers from the German Center for Neurodegenerative Diseases studied the association of pioglitazone and the onset of dementia in a prospective cohort study of 145,717 subjects aged 60 years or above who were free of dementia at baseline. The information on prescriptions of pioglitazone on a quarterly basis were implemented as a linear variable covering the time-dependent number of quarters of prescriptions which range between zero and 28 quarters. A Cox proportional hazard model was performed to explore the transition into dementia and to calculate the relative risk of dementia dependent on the use of pioglitazone adjusted for sex, age, use of NSAIDs, use of rosiglitazone, use of metformin and cardiovascular comorbidities including diabetes mellitus, cerebrovascular diseases, hypertension, ischemic heart diseases, atrial fibrillation and hypercholesterolemia.
During the follow-up period 13,841 subjects developed dementia. The relative risk of dementia reduced significantly (HR=0.94, p=0.004) with each additional quarter of pioglitazone prescription. Further analysis are done by converting numbers of quarters with prescriptions into prescribed doses of pioglitazone using the daily defined dose (DDD). Also these results support the initial hypothesis.
The researchers concluded that the long-term use of pioglitazone reduces the risk of dementia incidence in health claims data. They speculated that one possible pathway is via suppressing neuroinflammation.
- Pioglitazone has been found to reduce the risk of diabetic patients in developing Alzheimer’s disease.
- There is approximately a 20% reduction in risk of dementia in patients taking pioglitazone compared to patients taking insulin.
The Effect of the Prescription of Pioglitazone on the Incidence of Dementia presented July 21 2014 at the annual meeting of the Alzheimer’s Association International Conference in Copenhagen