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.
Wilkinson
D
D
Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK. david.wilkinson@wht.nhs.uk
Doody
R
R
Helme
R
R
Taubman
K
K
Mintzer
J
J
Kertesz
A
A
Pratt
R D
RD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000453:epidemiology; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil