These results are from a 24-week randomized, double-blind, placebo-controlled, multicenter US study ending with a single-blind placebo washout phase of 6 weeks in patients with mild to moderate Alzheimer’s disease. Patients were randomized to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154) or 10 mg/d donepezil (n = 157). A total of 473 patients were randomized.

Mean Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) scores for the placebo group improved after 6 weeks compared with baseline but steadily worsened at each 6-week interval thereafter.

The graph illustrates that in the intent-to-treat–last observation carried forward (ITT-LOCF) population, ADAS-Cog performance for donepezil-treated patients did not deteriorate with time. A statistically significant treatment effect versus placebo was found at 12 and 18 weeks as well as at the study end point (week 24).

At 24 weeks, improvements of 0.67 point and 1.06 points in ADAS-Cog scores from baseline were observed for the 5- and 10-mg/d donepezil groups, respectively, whereas the mean score for the placebo group deteriorated 1.82 points. Mean drug-placebo differences were 2.5 points and 2.9 points for the 5- and 10-mg/d dosage groups, respectively (P<.0001). The effect size for the 10-mg/d group was greater than that for the 5-mg/d group, but the differences between the active treatments were not statistically significant.

No residual beneficial effect on cognition was observed at week 30 (after the 6-week washout period).