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

Am J Geriatr Psychiatry. 2005 Nov;13(11):950-8. doi: 10.1176/appi.ajgp.13.11.950.


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 (Abeta) 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 Abeta 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 Abeta levels were unchanged from baseline for subjects receiving rosiglitazone but declined for subjects receiving placebo, consistent with recent reports that plasma Abeta42 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Amnesia / diagnosis
  • Amnesia / drug therapy*
  • Amnesia / psychology
  • Amyloid beta-Peptides / blood
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Mental Recall / drug effects
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Outcome Assessment, Health Care
  • PPAR gamma / agonists
  • Pilot Projects
  • Retention, Psychology / drug effects
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage*
  • Thiazolidinediones / adverse effects


  • Amyloid beta-Peptides
  • Hypoglycemic Agents
  • Insulin
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone