my personal edition > neurologic other > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Cholinesterase Inhibitor Therapy Has Limited Effect on Dementia, But Could Be a Brain Aid for Some Vascular Subcortical Subtypes: Presented at ISC

By Carole Bullock

NEW ORLEANS -- February 25, 2008 -- Patients with vascular dementia who were treated with the cholinesterase inhibitor donepezil did not have improvements in cognitive function, but some did perform better on tests that measure executive function in a study presented here at the International Stroke Conference (ISC) 2008.

Martin Dichgans, MD, Professor of Neurology, University of Muenchen, Muenchen, Germany, reported the results at a news conference of late-breaking clinical trials on February 22. The study is published simultaneously in the February 22 issue of The Lancet Neurology.

The trial was designed to test the efficacy of cholinesterase inhibitors for treatment of a genetic form of subcortical ischaemic vascular dementia because recent trials have shown that this drug class has a significant benefit on cognition in patients with vascular dementia, Dr. Dichgans said.

The double-blind, randomised study was initiated in January 2005 and included 86 patients with an average age of 55 years. Patients were treated with an 18-week regimen of donepezil 5 mg daily for the first 6 weeks and 10 mg daily for the subsequent 12 weeks. A control group of 82 patients received placebo.

Cognitive ability was tested with the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B times, the Vascular-Alzheimer's Disease Assessment Scale - Cognitive subscale (V-ADAS-cog), and the Executive Interview Test (Exit-25).

To be included in the trial, patients had to have an MMSE score of 10 to 27 and a TMT B-time score that was 1.5 standard deviation (SD) below the mean.

Baseline characteristics were similar in the 2 groups, with about 80% of patients having a history of stroke or transient ischaemic attack. However, there were more men in the placebo group (61%) compared with the donepezil group (46%).

The primary endpoint was change from baseline to week 18 in V-ADAS-cog score. The secondary endpoint combined a variety of other cognitive tests.

Analysis for the primary endpoint was an intention-to-treat population with the last observation carried forward (LOCF).

There were no significant differences in V-ADAS-cog between the two treatment groups, but there were significant differences in TMT B time (P = .005), TMT A time (P = .01), and Exit-25 (P = .02), Dr. Dichgans said.

"The median time to complete the TMT B test was 105 seconds in the treated patients versus 166 seconds in the placebo [patients]," Dr. Dichgans said. Compared with baseline, donepezil-treated patients had higher completion rates than placebo patients (78% vs 75%) at 18 weeks LOCF.

The drug was well tolerated, with adverse events rates of 7.3% in the placebo group and 10.5% in the donepezil group.

The beneficial effects shown on TMT B score and other executive tests are of "great interest," Dr. Dichgans said, because it means "there's an anatomical and pathophysiological basis to explain the beneficial effects ... for subcortical vascular cognitive impairment."

He suggested that the TMT test should be included as an outcome measure in future intervention trials, and that anticholinergics should be used to target patients with subcortical vascular dementia.

The study is sponsored by Eisai. Dr. Dichgans is a consultant for Eisai.


[Presentation title: Donepezil in Patients With Subcortical Vascular Cognitive Impairment: A Randomized Double-Blind Trial in CADASIL. Abstract LB5]

E-Mail this DGDispatch to a colleague

To print, use this version