Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone - A preliminary study

Objective: Insulin resistance ( impaired insulin action) has been associated with Alzheimer disease ( AD) and memory impairment, independent of AD. Peroxisome proliferator-activated receptor-gamma ( PPAR-gamma) agonists improve insulin sensitivity and regulate in-vitro processing of the amyloid precursor protein (APP). Authors evaluated the effects of the PPAR-gamma agonist rosiglitazone on cognition and plasma levels of the APP derivative beta-amyloid (A beta) in humans. Methods: In a placebo-controlled, double-blind, parallel-group pilot study, 30 subjects with mild AD or amnestic mild cognitive impairment were randomized to a 6-month course of rosiglitazone ( 4 mg daily; N = 20) or placebo ( N = 10). Primary endpoints were cognitive performance and plasma Ab levels. Results: Relative to the placebo group, subjects receiving rosiglitazone exhibited better delayed recall ( at Months 4 and 6) and selective attention ( Month 6). At Month 6, plasma A beta levels were unchanged from baseline for subjects receiving rosiglitazone but declined for subjects receiving placebo, consistent with recent reports that plasma A beta 42 decreases with progression of AD. Conclusions: Findings provide preliminary support that rosiglitazone may offer a novel strategy for the treatment of cognitive decline associated with AD. Future confirmation in a larger study is needed to fully