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 (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.
Watson
G Stennis
GS
Geriatric Research, Education, and Clinical Center, Research and Development Service, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Cholerton
Brenna A
BA
Reger
Mark A
MA
Baker
Laura D
LD
Plymate
Stephen R
SR
Asthana
Sanjay
S
Fishel
Mark A
MA
Kulstad
J Jacob
JJ
Green
Pattie S
PS
Cook
David G
DG
Kahn
Steven E
SE
Keeling
Michelle L
ML
Craft
Suzanne
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000647:Amnesia / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000097:blood; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D047495:PPAR gamma / Q000819:agonists; D010865:Pilot Projects; D012153:Retention, Psychology / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects
D016229:Amyloid beta-Peptides; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone