The recent article by Geldmacher et al1 describes the peroxisome proliferator–activated receptor γ (PPARγ) agonist pioglitazone trial for patients with Alzheimer disease (AD). Pioglitazone was generally well tolerated during 18 months of exposure, but no efficacy was demonstrated on clinical outcome measures.
Thiazolidinediones have beneficial effects in animal models of AD, but the efficiency of PPARγ agonists for treatment in mild to moderate AD remains unclear. Beneficial effects of rosiglitazone were first described in APOE-4 –negative patients with AD.2 However, repeated trials with rosiglitazone have not demonstrated consistent results.2 Pioglitazone treatment in diabetic patients with AD improved cognitive function as well as regional cerebral blood flow after a 6-month interval.3 I have experienced several cases in which pioglitazone has been protective against cognitive decline in AD over 24 months.4 In this connection, there might be unidentified factors that influence thiazolidinedione therapy for AD.
Sakurai T. Targets of the Peroxisome Proliferator–Activated Receptor γ Agonist Trials for the Prevention of Alzheimer Disease. Arch Neurol. 2011;68(4):542-543. doi:10.1001/archneurol.2011.57