Donepezil in vascular dementia: a randomized, placebo-controlled study

Objective: To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia (VaD).Methods: Patients (n = 616; mean age, 75.0 years) with probable or possible VaD, according to National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche en l’Enseignement en Neurosciences criteria, were randomized to receive donepezil 5 mg/day (n = 208), donepezil 10 mg/day (after 5 mg/day for the first 28 days) (n = 215), or placebo (n = 193) for 24 weeks.Results: Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3% of the 10 mg donepezil group and 80.8% of the 5 mg group completed the study compared with 83.4% of the placebo group. Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer’s Disease Assessment Scale–cognitive subscale compared with placebo, with a mean endpoint treatment difference, as measured by the change from baseline score, of approximately 2 points (donepezil 5 mg, -1.65 [p = 0.003]; 10 mg, -2.09 [p = 0.0002]). Greater improvements on the Clinician’s Interview-Based Impression of Change–plus version were observed with both donepezil groups than with the placebo group (overall donepezil treatment vs placebo p = 0.008); 25% of the placebo group showed improvement compared with 39% (p = 0.004) of the 5 mg group and 32% (p = 0.047) of the 10 mg group. Withdrawal rates due to adverse events were low (placebo, 8.8%; donepezil 5 mg, 10.1%; 10 mg, 16.3%).Conclusions: Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated