Alzheimer’s drug does not improve cognitive ability score in hereditary vascular dementia

International Stroke Conference Late-Breaking News:

NEW ORLEANS, Feb. 22 — A drug typically used to treat Alzheimer’s is not effective against cognitive decline in the early-onset hereditary form of vascular dementia called CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), according to late-breaking science reported today at the American Stroke Association’s International Stroke Conference 2008.

In a study titled, “Donepezil in Subcortical Vascular Cognitive Impairment: a Randomised, Double-Blind Trial in CADASIL,” international researchers evaluated the efficacy and safety of the drug donepezil in patients with CADASIL. 

Donepezil is a cholinesterase-inhibiting drug used to treat Alzheimer’s disease.

The 18-week, double-blind, multi-national study compared 10 milligrams of donepezil to placebo in patients with declining cognitive ability documented by either the Mini-Mental State Examination (MMSE) or the Trail Making Test (TMT), said Martin Dichgans, M.D., professor of neurology at the University of Muenchen in Germany and the study’s presenting author.

Researchers’ primary goal was for patients to register an improvement in cognitive ability on the Vascular-Alzheimer’s Disease Assessment Scale-Cognitive subscale (V-ADAS-cog). Their secondary goal was for patients to register an improvement in cognitive ability on a variety of other tests, including tests on specific aspects of cognition.

Researchers randomly chose 168 patients, average age 54, to participate.

The researchers reported no statistical difference between donepezil and placebo on the primary goal.   However, they reported a treatment effect favoring donepezil on several executive function tests including the TMT.

Discontinuations due to adverse events were slightly more frequent in patients receiving donepezil (11.6 percent) than in patients receiving placebo (8.5 percent).

The researchers concluded that “donepezil had no effect on the V-ADAS-cog in CADASIL patients with cognitive impairment.”   They further conclude that the observed treatment effect on executive function tests raises interesting hypotheses and that their findings may have implications for future trial design in vascular dementia.

Eisai Medical Research Inc. (Ridgefield Park, N.J.) supported the study. Several authors receive funding from Eisai Inc. and Pfizer, Inc.

Disclosures: Dichgans: consultant to EISAI, M,G; Research Grant, S,B, Travel Grant.
Note: Donepezil has not been labeled for use in CADASIL