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Down Syndrome Abstract
of the Month: Jan 2003

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Donepezil for the treatment of language deficits in adults with Down syndrome: A preliminary 24-week open trial

Heller JH, Spiridigliozzi GA, Sullivan JA, Doraiswamy PM, Krishnan RR, Kishnani PS
Am J Med Genet 2003 Jan 15;116(2):111-6

Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

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At present, there is no proven pharmacologic treatment for cognitive or language impairments in Down syndrome (DS). Cholinergic deficits have been documented in DS and linked to cognitive deficits. This study is a 24-week open-label clinical trial of donepezil hydrochloride for the treatment of language deficits in adults with DS. To our knowledge, this is the first prospective study to evaluate systematically the effects of donepezil, a cholinesterase inhibitor, on specific language domains in DS. The main finding that emerged was an improvement in expressive language performance following donepezil therapy. Despite the multiple methodological limitations, the results raise important questions regarding the role of the cholinergic system in language function and the specific effect of cholinergic therapy in the treatment of language impairment in DS. The results support the need for large-scale controlled studies of the effects of donepezil treatment on language and on other cognitive domains in DS.

My comments:

I normally don't like to cover two studies on the same subject back-to-back, but I'm writing about a donepezil study two months in a row due to the interest generated by this medication. For background, see the April '99 abstract and the Dec. '02 abstract.

This is another adult study (we're still waiting for publication of the Duke schoolchild donepezil study), but where last month's study looked at behavioral results, this study looks at language.

Six adults with Down syndrome were examined in this study; none of the participants had ever had any other investigational or alternative therapies prior to the study. The adults were between the ages of 20 and 41 years of age, and tested IQs ranged from 40 to 60. The adults were tested for language skills using the Test of Problem Solving (TOPS) at the start of the study period, after 12 weeks and after 24 weeks of using donepezil; and the Clinical Evaluation of Language Fundamentals, revised (CELF-R) at the start of the study period and after 24 weeks of using donepezil. TOPS consists of having the subject verbally identify reasonable solutions to problems presented via pictures. The CELF-R test assesses language form and content. Overall, the donepezil was well tolerated, with the main side effect being mild diarrhea.

TOPS test results showed a significant improvement after 12 weeks of donepezil over the results at the start of the testing period; there was no difference in test results between the tests given at 12 weeks after donepezil and after 24 weeks of donepezil. The authors report that the improvement seen on this test was equivalent to more than one-half the expected gain expected by the average 5 year-old in 1 year of development, which is a fairly rapid gain. The CELF-R results were more complicated, with improvement seen in the adults with the higher language skills at the start of the study but no significant difference in the adults with lower language skills at the start of the study.

Again, this should be regarded as a preliminary study. The number of subjects studied was small, there were some problems with the actual test giving that may infer observer bias, and there was no control (placebo) group. The next step will be to study a larger group of people with DS and to include a control group. But these results, along with the anticipated improvement of the quality of life that comes with improved language skills, are enough to warrant more testing with donepezil.


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