title: An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients.
abstract: BACKGROUND
  Impairments in cognition and motivation are common after stroke and predict poor functional recovery. Pharmacological agents that enhance cognition and/or diminish apathy may, when combined with traditional rehabilitative efforts, improve functional recovery. We investigated the feasibility of using acetylcholinesterase inhibitors in older patients with acute post-stroke cognitive impairment and examined their effects on functional recovery.
  
  
  METHODS
  This 12-week open-label study prospectively treated ischemic stroke survivors aged > or =60 years who were undergoing inpatient rehabilitation and who had cognitive impairment in one or more domains (memory, attention or executive function). Participants received galantamine (maximum dose 24 mg/day) or donepezil (maximum dose 10 mg/day). Physical function was assessed using the Functional Independence Measure-motor subscale (FIM-motor); participants' functional gains were compared to those of a matched historical comparator group. Changes in cognition and apathy were also assessed. Since donepezil and galantamine have different pharmacologic profiles, they were examined separately.
  
  
  RESULTS
  Forty participants started study medication; 14 participants terminated prematurely. Donepezil-treated participants experienced a 14-point greater improvement in the FIM-motor score compared to either galantamine-treated participants or the historical comparator group (repeated measures mixed model, group x time interaction p < 0.0001). Change in apathy, but not in cognition, was also associated with change in the FIM-motor score.
  
  
  CONCLUSIONS
  In this open-label study, participants receiving donepezil had better functional recovery than participants receiving galantamine or the historical comparators. This improvement may reflect efficacy at the starting dose for donepezil but not galantamine. A randomized trial is in progress.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Whyte
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.forename: Meryl
authors.initials: M
authors.lastname: Butters
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Skidmore
authors.forename: Kris
authors.initials: K
authors.lastname: Koenig
authors.forename: Mary Amanda
authors.initials: MA
authors.lastname: Dew
authors.forename: Louis
authors.initials: L
authors.lastname: Penrod
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Leonard
authors.initials: L
authors.lastname: Cabacungan
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
authors.forename: Michael C
authors.initials: MC
authors.lastname: Munin
mesh_terms: D000368:Aged; D001288:Attention / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D000077265:Donepezil; D005240:Feasibility Studies; D005260:Female; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D020127:Recovery of Function; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil