Chronic donepezil treatment is associated with slowed cognitive decline inAlzheimer's disease

Objective: To compare of cognitive decline between probable Alzheimers dise ase (AD) patients with long-duration cholinesterase inhibitors (chE-Is) and those who remained untreated. Background: ChE-Is, including donepezil and tracrine, have shown beneficial effects on cognition and global functioning in patients with AD. The duration of these benefits is unknown because the longest double-blind placebo-controlled studies reported were only approxi mately 6 months long. Ethical concerns regarding randomization of patients to placebo for long periods make it difficult to undertake trials of longer duration. Methods: We identified patients in 4 AD centers who were or were not consistently treated with ChE-Is and who had demographic, psychometric and follow-up data. We compared 205 ChE-I-treated and 218 untreated AD pat ients on baseline variables hypothesized to differ between these groups, on baseline Mini Mental Status Examination (MMSE) scores and on rates of MMSE change at 1 year. The analysis was performed initially with all ChE-I-trea ted patients as a single group versus untreated subjects, and then with don epezil versus untreated subjects and tacrine versus untreated subjects. Res ults: As expected, treated and untreated patients differed with respect to age, education, ethnicity, percentage of com m unity dwelling and exact day s of follow-up (ANOVA and chi (2)) in several comparisons, but did not diff er on baseline MMSE score. These baseline variables were highly intercorrel ated. MMSE scores declined significantly more slowly after 1 year of ChE-I treatment compared to untreated patients (p = 0.05) after controlling for b aseline differences in age, education, ethnicity and percentage of communit y dwelling. Slowing of decline was significant in the donepezil-treated pat ients (p = 0.007) but not in the tacrine-treated group (p = 0.33). Conclusi ons: This study, utilizing concurrent, nonrandomized controls, suggests tha t donepezil continues to have efficacy over at least the first year of ther apy. Other studies are needed to determine whether the benefits are maintai ned beyond 1 year. Copyright (C) 2001 S. Karger AG, Basel.