A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD

Objective: To evaluate the long-term clinical efficacy and safety of donepe zil versus placebo over 1 year in patients with mild to moderate AD. Method s: Patients (n = 286; mean age, 72.5 years) with possible or probable AD fr om five Northern European countries were randomized to receive either donep ezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. Results: The study was completed by 66.9% of the donepezi l- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Brsne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.0 5) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cogni tion and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by t he Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7%, of donepezil- and 75.7% of pl acebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated p atients discontinuing because of AE. Treatment response to donepezil was no t predicted by APOE genotype or sex in this population. Conclusion: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tole rated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.