Cholinergic Therapy For Down's Syndrome
One of the changes noted in adults with Down syndrome as they age is the loss of certains neurons in the brain; specifically, those using the neurotransmitter acetylcholine. These are called cholinergic neurons. The acetylcholine is secreted from one neuron into the space between it and one or more other neurons. The space, or connection bewteen the neurons, is called the "synapse." In this manner, the acetylcholine gives a message to the surrounding neurons to either fire or not to fire. This "communication" between neurons is responsible for all neurologic processes.
Cholinergic deficits have been linked to cognitive difficulties such as memory loss. This same phenomemon is seen in Alzheimer's disease. Donezepil (Aricept) is a drug classified as an acetylcholinesterase inhibitor. What that means is that donezepil keeps the body from degrading the secreted acetylcholine, leaving it around in the synapse for increased neurologic activity. Donezepil was approved by the US FDA in 1998 for the treatment of cognitive impairment of Alzheimer's disease. The Duke researchers speculated that since the neuroanatomic changes of Down syndrome are similar to Alzheimer's, donezepil might help in adults with Down syndrome also.
Four adults with Down syndrome ages 24, 27, 38 and 64 were given donezepil. The two older patients met the clinical definition of having dementia. The drug was given for 6 months, with no significant side effects seen. The results were assessed using the Vineland Adaptive Behavior Scales. At the end of 6 months, the authors report that there were "improvements in communication, expressive language, attention and mood stability." Most improvements occurred in the first 3 months of the study. Both of the older patients had improved socialization skills. No placebos were used.
A very small study with the problems of not being a controlled or blinded study. However, that wasn't its purpose. The goal of this study was to show that some effects could be seen and that this should justify a larger, controlled, double-blinded study, and it fulfilled those goals. I understand that these researchers are going ahead with such a study. If donezepil works as well as the pilot study suggests, this will be a boon for adults with DS.
Duke University Medical Center,Durham, NC, USA.
Lancet 353: 1064, 1999.
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