Acetylcholinesterase Inhibitors to Improve Cognitive Function and Overall Rehabilitation After a Stroke

Cognitive impairment is a common result of a stroke and can be detrimental to recovery. It
can negatively affect both mental and physical functioning, thereby complicating the
rehabilitation process. Although much research has targeted the effects of long-term
cognitive impairment after a stroke, very little research has been done to examine the
incidence and course of cognitive impairment during the first three months following a
stroke. These first three months are the most important in terms of regaining function.
Acetylcholinesterase inhibitors have been beneficial to both sufferers of vascular dementia
and Alzheimer's disease. They may also be a useful pharmacologic intervention to enhance
post-stroke rehabilitation. This study will compare the effectiveness of two
acetylcholinesterase inhibitors, galantamine and donepezil, in improving cognitive function
and overall rehabilitation in elderly stroke survivors.

Participants in this open label study will be randomly assigned to receive either galantamine
or donepezil for 12 weeks. Participants assigned to receive galantamine will receive 4 mg
twice a day for 4 weeks, 8 mg twice a day for the next 4 weeks, and 12 mg twice a day for the
remainder of the study. Participants assigned to receive donepezil will receive 5 mg twice a
day for 6 weeks, and then 10 mg twice a day for the next 6 weeks. Functional independence
will be measured at baseline and Weeks 2 and 12. In addition, a pre-stroke level of
functional independence will be obtained through a structured interview with participants and
their families. Participants will also be monitored for signs of depression and medication
side effects throughout the study.

Inclusion Criteria:

- Admitted to a rehabilitation hospital with primary diagnosis of ischemic stroke
(cardiovascular accident)

- Stroke was within 30 days of being admitted

- Medically stable

- Presence of memory and/or attentional impairments and evidence that these impairments
were not present or were less severe prior to the stroke (assessed via interview with
family)

- Approval by individual's attending physician at the rehabilitation hospital

Exclusion Criteria:

- Aphasia or cognitive (or behavioral) impairments severe enough to prevent valid
neuropsychiatric assessment

- Currently experiencing a major depressive episode (unless treated and in partial
remission, assessed using the Primary Care Evaluation of Mental Disorders)

- Current psychosis or mania

- History of substance or alcohol abuse or dependence within three months of study entry

- Currently taking a cholinomimetic drug

- Medical condition with known sensitivity to donepezil (e.g., slower than normal heart
rate, supraventricular cardiac conduction defects, severe asthma or obstructive
pulmonary disease, active upper gastrointestinal bleed, or gastric/duodenal ulcer if
not on acid-blocking agent)

- Informed that taking donepezil is medically inadvisable

- Current use of any anticholinergic medication (e.g., for bladder spasm)