An Open-Label Pilot Study of Acetylcholinesterase Inhibitors to Promote Functional Recovery in Elderly Cognitively Impaired Stroke Patients

Abstract

Background: Impairments in cognition and motivationare 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 ≧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 × 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.

Poststroke Apathy

“…Two articles reported on apathy prevalence in the same cohort at different time points. 23,44 Results reported in these articles were combined using size weighted averages for all analyses except for those regarding time since stroke and population age.…”

“…43 In another small (n=22) open study, the acetylcholinesterase inhibitor donepezil had a modest beneficial effect on functional status, which was also associated with a reduction in apathy score. 44 In 5 case reports, a favorable effect of treatment with bromocriptine was reported, 14,[45][46][47][48] and in 3 with methylphenidate.…”

“…Evidence for an advantageous effect of the acetylcholinesterase inhibitor donepezil in patients with acute poststroke cognitive impairment compared with a retrospective control group is circumstantial. 44 A number of case reports describing a beneficial effect …”

Safety of Pharmacological Augmentation of Stroke Rehabilitation

“…), selective serotonin noradrenaline reuptake inhibitors (SNRI) [25] (reboxetine 3 mg b.i.d. ), acetylcholinesterase inhibitors [6,7] (donepezil 5 mg q.d. ), modafinil [26,27] (100 mg/day), methylphenidate [9] (20 mg/day), and memantine [28] (20 mg/day).…”

“…Indeed, some clinical studies showed a beneficial effect with different agents [3,4,5,6,7,8,9] while others did not [10,11,12,13,14,15]. Thus, the clinical evidence of benefit of this treatment approach is weak, as most of the aforementioned studies are limited by small sample sizes and narrow inclusion criteria.…”