NEW YORK (Reuters Health) – Patients with vascular dementia who took the acetylcholinesterase inhibitor donepezil had mild improvements in cognitive function, but not global function, in an international trial reported online April 16th in Stroke.

 
Donepezil is given to patients with Alzheimer’s disease, and as in that population, “cholinergic deficits and disruption of cholinergic pathways occurring in some patients with vascular dementia may contribute to cognitive impairment,” according to the researchers. This possibility formed the rationale for their study, along with results of smaller donepezil studies showing cognitive improvement but “inconsistent” global function benefits.

In the 24-week randomized trial, 648 patients took donepezil (5 mg/day) and 326 took placebo. The investigators used the Vascular-Alzheimer Disease Assessment Scale-Cognitive Subscale to measure cognitive function, and the Clinician’s Interview-Based Impression of Change plus caregiver interviews to assess global function.
 

The donepezil group had a “small but significant” increase from baseline in cognitive subscale score at 12 and 18 weeks (p < 0.05) and at 24 weeks (p < 0.001). The placebo group showed “relative stability.”   On intention to treat analysis, global function was no different in the two groups. Cochran-Mantel-Haenszel analysis of the distribution of responses to the clinician interview tool did show a benefit of donepezil at 18 and 24 weeks – but multivariate analysis confirmed a significant effect only at week 18. “The Clinician’s Interview-Based Impression of Change, plus caregiver interview is notoriously insensitive to change and is based on the subjective impression of the observer,” said lead author Dr. Gustavo Roman of the Methodist Neurological Institute in Houston, Texas in email to Reuters Health. “In chronic conditions such as vascular dementia or Alzheimer disease, it becomes very difficult for observers to notice change.”   Dr. Roman and colleagues had magnetic resonance imaging results for 681 of their subjects, which showed hippocampal atrophy in 54%. When the research team analyzed outcomes only in the patients with hippocampal atrophy, they saw stable or slightly improved cognition in the donepezil group and cognitive decline in the placebo group.   Dr. Roman said the atrophy results indicate the possibility of underlying Alzheimer’s disease. “It also points to the need to develop objective markers for future controlled clinical trials in order to avoid the uncertainties of subjective responses,” he said.   Reference:
Stroke 2010.