The paper, entitled 鈥淭he NIH Toolbox Cognitive Battery for Intellectual Disabilities: Three preliminary Studies and Future Directions,鈥� was published today in the Journal of Neurodevelopmental Disorders.
David Hessl, professor in the Department of Psychiatry and Behavioral Sciences and lead author of the paper, said the findings, if validated in a larger study now under way, could change the course of research on treatments for intellectual disabilities and other neurodevelopmental disorders, particularly in the area of drug therapy.
鈥淲e used to think that intellectual disabilities were stable and very difficult to remediate,鈥� Hessl said. 鈥淏ut cutting-edge research in the animal models of some forms of intellectual disabilities suggests that meaningful improvements in cognition are possible. Having the ability to measure cognitive change could give new impetus to drug developers to create therapies targeted to the genetic mutations responsible for intellectual disabilities that could be used in clinical trials. The greater goal is to find treatments 鈥� both pharmaceutical and behavioral 鈥� that improve overall function in people with these disabilities.鈥�
Hessl鈥檚 pilot studies used a National Institutes of Health battery of tests, developed in young children, adolescents and adults from the general population, to determine whether it would reliably measure change in cognitive function in people with intellectual disabilities, who tend to be very difficult to accurately assess.
Hessl enrolled participants of varying ages with fragile X syndrome, Down syndrome and other causes of intellectual disability, including those with autism, in three studies that examined tests to measure cognitive flexibility, inhibition and visual attention, episodic memory, working memory, processing speed, oral reading and receptive vocabulary, calculating each person鈥檚 performance relative to his or her age-matched peers from the general population.
After extensive analyses, the pilot studies showed overall that the NIH cognitive battery is feasible, reliable and valid as a cognitive measurement tool for a high proportion of participants, and that it is very well aligned with another measure of intelligence.
Hessl cautions that the findings are based on pilot studies involving relatively small numbers of participants and are not yet ready for use in clinical trials or other applications. Hessl and colleagues are currently in the first of a four-year, multi-site study of the tests on a larger scale and over a longer time period that will provide a much clearer picture of how well they works.
The history of drug development for people with intellectual disabilities has been frustrating, Hessl said, because while drugs showed much promise in animal models of some conditions, like fragile X, they have not fared well in recent human clinical trials.
鈥淚t has been a rollercoaster for everyone in the field, including the families,鈥� he said. 鈥淭he targeted treatment was well worked out in animal models. A lot of the abnormalities in the fragile X mice were normalized by these drugs. All the families and many of us in the field were excited.鈥�
He explained that while the earlier trials attempted to measure changes in behavior 鈥� typically the greatest challenge for parents of children with intellectual disabilities 鈥� cognitive measures were not used.
鈥淐ognitive measures could be really useful, because they are less affected by the placebo effect and are more objective,鈥� he said. 鈥淚 still feel confident that these targeted treatments can work with the right refinement of study design, and I think our lab is really well set up to help with this effort. If we can make headway, we could really change the course of research on treatment of neurodevelopmental disorders.鈥漈he study was funded with a grant from the National Institute of Child Health and Human Development, number HD076189.
Other researchers included Stephanie Sansone, Leonard Abbeduto and Andrea Schneider of UC Davis, E. Berry-Kravis, K. Rhodes and D. Oaklander of Rush University Medical Center, K. Widaman of UC Riverside, K. Riley and J. Coleman of the University of Denver and R. Gershon of Northwestern University.
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