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. Design: 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 MiniMental 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. Conclusion: 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.