Back in the 90's, a woman named Dixie Lawrence made a splash on the internet by claiming to have cured Down Syndrome in her daughter using nutritional supplements and piracetam a so-called "smart drug". It is unclear whether the apparent improvement continued because she disappeared from public view, but one of the things she said during that time that struck me as interesting was that her daughter was nearly behaviorally normal when she was born. In other words Down Syndrome is a developmental problem - the cognitive deficits increase with age.

Now studies are confirming the developmental aspect of Down Syndrome's effects on learning. Researchers at Stanford have linked the cognitive deficits associated with Down Syndrome with neuronal breakdown in an area responsible for mediating the formation of memories in the hippocampus. When memories are being formed, neurons in an area called the Locus Coreolus use norepinephrine to carry information to areas of the hippocampus which perform contextual discrimination and allow important learning processes to take place.

When the neurons in the Locus Coreolus break down or don't exist in great enough numbers, contextual and spatially encoded memories can't be created, and it is much harder to learn many types of tasks. Interestingly, what are called "Cued recall" tasks, in which memory is elicited by sensory cues like color or sound, are not affected, because they are controlled by a different area of the brain. As children with Down syndrome age they fall further and further behind because they can't use spatial and contextual information to learn as well as normal children.

It's important to note that the receptors for the neurotransmitters exist, but they simply don't get the chemical messages they need to perform their tasks. The Stanford study used this fact to try to improve learning performance in the mouse model of Down Syndrome by restoring normal concentrations of norepinephrine in the brain, using the norepinephrine precursor drug Droxidopa. The mice, who had cognitive deficits resulting in impaired nesting behaviors improved rapidly.

The authors suggest that it may be possible to treat Down Syndrome-related cognitive disability in humans by improving norepinephrine neurotransmission using targeted drugs such as Droxidopa.