An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients

Cerebrovasc Dis. 2008;26(3):317-21. doi: 10.1159/000149580. Epub 2008 Jul 31.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Attention / drug effects
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition / drug effects*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cognition Disorders / psychology
  • Donepezil
  • Feasibility Studies
  • Female
  • Galantamine / adverse effects
  • Galantamine / therapeutic use*
  • Humans
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Male
  • Middle Aged
  • Motivation
  • Motor Activity / drug effects
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Pilot Projects
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Prospective Studies
  • Recovery of Function
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Stroke / psychology
  • Treatment Outcome

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Nootropic Agents
  • Piperidines
  • Galantamine
  • Donepezil