Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial.
OBJECTIVE
To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease.


METHODS
Multicenter, randomized, double-blind, 24-week, placebo-controlled study that enrolled patients with early-stage Alzheimer disease. Patients were randomized in an approximately 2:1 ratio to donepezil, 5 mg/d, for the first 6 weeks, with a forced escalation to 10 mg/d thereafter (n = 96), or placebo (n = 57). The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale. Secondary efficacy measures included the Mini-Mental State Examination, the Computerized Memory Battery Test, the Clinical Dementia Rating Scale-Sum of the Boxes, the Patient Global Assessment Scale, and the Apathy Scale.


RESULTS
Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point (last observation carried forward); treatment differences were 1.9 (P = .03), 2.3 (P = .008), and 2.3 (P = .001) points, respectively. Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6, 12, and 24 and at the end point (last observation carried forward); treatment differences were 1.4 (P = .02), 1.2 (P = .04), 1.4 (P = .03), and 1.8 (P = .002) points, respectively. Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales: facial recognition (P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population), first and last name total acquisition (P = .02), and name-face association delayed recall (P = .04). Donepezil was safe and well tolerated in this population; serious adverse events occurred in similar numbers of donepezil- and placebo-treated patients.


CONCLUSIONS
These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease, supporting the initiation of therapy early in the disease course to improve daily cognitive functioning.
Seltzer
Ben
B
Department of Psychiatry and Neurology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA. seltzer@tulane.edu
Zolnouni
Parvaneh
P
Nunez
Margarita
M
Goldman
Robert
R
Kumar
Dinesh
D
Ieni
John
J
Richardson
Sharon
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D016009:Chi-Square Distribution; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*
D007189:Indans; D010880:Piperidines; D000077265:Donepezil