Executive Cognitive Function In CADASIL Patients May Be Improved By Taking Donepezil

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Main Category: Alzheimer's / Dementia
Also Included In: Stroke;  Neurology / Neuroscience;  Clinical Trials / Drug Trials
Article Date: 26 Feb 2008 - 0:00 PDT

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According to an article published in the April edition of The Lancet Neurology, donepezil may improve the executive function of patients who suffer from the CADASIL form of vascular dementia. However, researcher Martin Dichgans of Ludwig Maximilian University, Munich, Germany and colleagues found that donepezil did not improve patients' cognitive score.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a genetic form of vascular dementia (due to vascular lesions in the brain) and the most common form of hereditary stroke disorder. It tends to begin with migraine headaches and strokes in middle-aged patients. Executive functions are the high-level cognitive processes that facilitate new ways of behaving, and optimize one's approach to unfamiliar circumstances.

Donepezil is a type of cholinesterase inhibitor (CI) that can benefit functions of brain, body, and daily living activities in patients with mild to moderate Alzheimer's disease (AD). In the elderly, it is quite common to have AD along with vascular dementia. One of the difficulties in testing CI drugs is due to the fact that it is not clear whether the drug benefits have been caused by improvement in the vascular dementia or the AD. Since CADASIL has early onset in patients, it is possible to study people who only have CADASIL, without overlapping AD symptoms.

Dichgans and colleagues studied 168 patients in randomized controlled setting, all who had CADASIL and were between 25 and 70 years of age. The focus was to see if donepezil improved cognitive function. Over 18 weeks, 86 participants received 10 mg donepezil each day and 82 received placebo.

Main findings include:

• Donepezil did not significantly improve cognitive function as measured by V-ASAS-cog scores
• Donepezil resulted in a significant treatment improvement in a number of secondary outcomes such as:
• The times taken to perform specific tasks (TMT B time and TMT A time)
• An executive cognitive function assessment (EXIT25 - a 25-item interview scored between 0 and 50)

"Donepezil had no effect on the primary endpoint, the V-ADAS-cog score in CADASIL patients with cognitive impairment. Improvements were noted on several measures of executive function, but the clinical relevance of these findings is not clear," write the authors. Dichgans and colleagues note, however, that their findings can aid future trial design in subcortical vascular cognitive impairment.

An accompanying Reflection and Reaction written by Lon S. Schneider of University of Southern California Keck School of Medicine, Los Angeles, CA writes: "Dichgans and colleagues showed the feasibility of multi-center trials with patients with CADASIL and the therapeutic potential of cholinesterase inhibitors. In future trials, the sample selection should be reconsidered to define better the cognitive impairment syndrome to be treated, choose outcomes that reflect the deficits to be treated, and identify the individual patients who benefit from treatment."

Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL
The Lancet Neurology. February 22, 2008.
doi:10.1016/S1474-4422(08)70046-2
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Written by: Peter M Crosta
Copyright: Medical News Today
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