title: The long-term efficacy and tolerability of donepezil in patients with vascular dementia.
abstract: OBJECTIVE
  To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD).
  
  
  METHODS
  International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.7 +/- 0.3) with a diagnosis of possible or probable VaD and without a diagnosis of Alzheimer's disease, who were medically stable and had completed one of two double-blind studies. All patients received donepezil 5 mg/day for the first 6 weeks, then 10 mg/day (clinician approval required). Assessments were performed at week 6 and every 12 weeks thereafter. The main outcome measure was the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog). Safety/tolerability measures included adverse events (AEs) and physical and laboratory evaluations.
  
  
  RESULTS
  Of 1219 eligible patients, 885 (72.6%) were enrolled, of which 707 (79.9%) completed the study; 127 (14.4%) patients discontinued due to AEs. A mean reduction (0.6-1.15 points) from double-blind study baseline score to week 54 (end of open-label study) on the ADAS-cog was observed for patients who received donepezil continuously for 54 weeks. ADAS-cog scores remained stable in the group that initiated donepezil treatment during the extension study. Most common donepezil-related AEs were nausea (occurring in 5.3%) and diarrhoea (8.8%); no unexpected AEs attributable to donepezil occurred.
  
  
  CONCLUSIONS
  These data suggest that donepezil improves cognition for up to 54 weeks in patients with VaD. Patients initiating donepezil in this extension study did not perform as well on the primary outcome measure as those initiating donepezil in the double-blind study.
authors.affiliation: Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wilkinson
authors.forename: Gustavo
authors.initials: G
authors.lastname: Róman
authors.forename: Stephen
authors.initials: S
authors.lastname: Salloway
authors.forename: Jane
authors.initials: J
authors.lastname: Hecker
authors.forename: Karyn
authors.initials: K
authors.lastname: Boundy
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Holly
authors.initials: H
authors.lastname: Posner
authors.forename: Rachel
authors.initials: R
authors.lastname: Schindler
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000175:diagnosis / Q000188:drug therapy*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil