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Preserved Cognition in Patients With Early Alzheimer Disease and Amnestic Mild Cognitive Impairment During Treatment With Rosiglitazone

A Preliminary Study

Received December 1, 2004; revised April 21, 2005; accepted April 27, 2005. From the Geriatric Research, Education, and Clinical Center (GRECC) (GSW,BAC,MAR,LDB,SRP,MAF,JJK,DGC,MLK,SC) and the Research and Development Service, Veterans Affairs Puget Sound Health Care System (VAPSHCS), Seattle, WA (SEK), the Depts. of Psychiatry and Behavioral Sciences (GSW,BAC,MAR,LDB,MLK,SC), Medicine (SRP,PSG,DGC,SEK), Neurology (MAF), Psychology (JJK), and Pharmacology (DGC), Univ. of Washington School of Medicine, Seattle, WA, and GRECC, William S. Middleton Memorial Veterans Hospital, and Department of Medicine, University of Wisconsin School of Medicine, Madison, WI (SA). Send correspondence and reprint requests to Dr. Suzanne Craft, VAPSHCS, S-182-GRECC, 1660 S. Columbian Way, Seattle, WA 98108. e-mail: scraft{at}u.washington.edu
© 2005 American Association for Geriatric Psychiatry

Objective: Insulin resistance (impaired insulin action) has been associated with Alzheimer disease (AD) and memory impairment, independent of AD. Peroxisome proliferator-activated receptor- (PPAR-) agonists improve insulin sensitivity and regulate in-vitro processing of the amyloid precursor protein (APP). Authors evaluated the effects of the PPAR- agonist rosiglitazone on cognition and plasma levels of the APP derivative ß-amyloid (Aß) 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 Aß 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 Aß levels were unchanged from baseline for subjects receiving rosiglitazone but declined for subjects receiving placebo, consistent with recent reports that plasma Aß42 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 demonstrate rosiglitazone’s therapeutic potential.

Key Words: Alzheimer Disease • Outcome Studies • Insulin • Beta-Amyloid • Mild Cognitive Impairment

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