Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial.
BACKGROUND
Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms.


METHODS
In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function.


RESULTS
The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).


CONCLUSIONS
Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.
Doody
R S
RS
Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030, USA.
Ferris
S H
SH
Salloway
S
S
Sun
Y
Y
Goldman
R
R
Watkins
W E
WE
Xu
Y
Y
Murthy
A K
AK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D018450:Disease Progression; D000077265:Donepezil; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care / Q000379:methods; D010349:Patient Compliance / Q000706:statistics & numerical data; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil