Pioglitazone for the treatment of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD includes Anticholinesterase Inhibitors (AChEIs) for mild-moderate AD, and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly influencing the progression of the disease. Pioglitazone (AD4833) is an insulin sensitizer of the thiazolidinedione class of nuclear Peroxisome-Proliferator Activated Receptor γ (PPARγ) agonists. It binds to PPARγ, affecting gene transcription and reducing inflammation. Areas covered: This review discusses the history of Pioglitazone, its pharmacokinetics and pharmacodynamics profile, and safety issues, together with an overview of clinical trials carried out so far. A literature search was made in Pubmed for pioglitazone, AD, trial, and on the ClinicalTrials.gov site for clinical trials with Pioglitazone. Expert opinion: A Phase II study in AD, and its previous indication for diabetes, showed that Pioglitazone is safe and well tolerated. So far, two large Phase III trials are ongoing, but there are no preliminary results yet on a possible beneficial effect on cognition in patients with AD.