title: Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.
abstract: OBJECTIVE
  Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD.
  
  
  METHODS
  Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population.
  
  
  RESULTS
  At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo).
  
  
  CONCLUSIONS
  These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.
authors.affiliation: University of Toronto, Department of Medicine (Division of Neurology), Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Black
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Román
authors.forename: David S
authors.initials: DS
authors.lastname: Geldmacher
authors.forename: Stephen
authors.initials: S
authors.lastname: Salloway
authors.forename: Jane
authors.initials: J
authors.lastname: Hecker
authors.forename: Alistair
authors.initials: A
authors.lastname: Burns
authors.forename: Carlos
authors.initials: C
authors.lastname: Perdomo
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Raymond
authors.initials: R
authors.lastname: Pratt
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D002319:Cardiovascular System / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil