Donepezil Improves Executive Function After Vascular Stroke: Presented at AAN

By Ed Susman

CHICAGO -- April 15, 2008 -- The use of donepezil appears to improve some measures of executive function among individuals with a rare genetic disorder known as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

However, researchers were unable to show that the use of the cholinesterase inhibitor had any effect on cognition as measured by the Vascular-Alzheimer's Disease Assessment Scale Cognitive Subscale (V-ADAS-cog).

The 18-week, placebo-controlled, double-blind, multicentre trial was conducted in 10 countries. Patients were included if they had CADASIL and cognitive impairment as defined by the entry criteria. Patients in the donepezil group received 5 mg of donepezil once a day for the first 6 weeks of the trial and then 10 mg a day for the rest of the trial.

Researchers screened 267 patients; of those, 168 were randomised; 82 were assigned placebo and 86 were assigned donepezil. In the intent-to-treat population there were 77 patients in the placebo group and 84 patients in the donepezil group.

"The completion rate was very high -- 89% in the placebo group and 84.9% in the donepezil group -- and the demographics were well balanced," said Stephen Salloway, MD, Chief of Neurology and Director, Memory and Aging Program, Brown Medical School, Providence, Rhode Island.

"What we found from this study is that the V-ADAS-cog is not the appropriate test for people with CADASIL or other forms of vascular dementia," he added.

In a poster presentation on April 15 here at the American Academy of Neurology (AAN) 60th Annual Meeting, Dr. Salloway said that the use of the Alzheimer's-based test -- the primary endpoint of the study -- showed no changes in cognition over the 18-week period of the study.

"However, we found a significant treatment effect on several measures of executive function," he noted. "These were the Trail Making Test part A time (P = .012), the trail Making Test part B time (P = .005), and the Executive Interview 25 (P = .022)."

At no time during the trial did donepezil treatment differentiate from placebo on the study's primary measure. At week 6, patients treated with donepezil showed about a 0.7-point decline in V-ADAS-cog score compared with a 1.2-point decline among placebo patients (where a declining score indicates improvement).

At week 12, donepezil patients showed a 1.5-point decline in the score and placebo patients registered about a 0.6-point decline. After 18 weeks, placebo patients achieved a 0.81-decline in the scale compared with a 0.85-point decline in the donepezil group (P = .056).

No differences were seen in other broadly based tests, including the Mimi-Mental State Examination, Dr. Salloway said.

The rates for adverse events were similar for both the donepezil patients and the placebo patients.

The trial received support from Eisai Pharmaceuticals.

[Presentation title: Efficacy of Donepezil in CADASIL: A Model of Subcortical Vascular Cognitive Impairment. LLB1.004]