Authors: Rebecca Shields, Forrest McKenzie, Andrea Drayton, and Stephanie Sansone of UC Davis; Aaron Kaat and Richard Gershon of Northwestern University; Jeanine Coleman and Karen Riley of the University of Denver; Claire Michalak and Elizabeth Berry-Kravis of Rush University Medical Center; and Keith Widaman of the University of California, Riverside


Researchers at the UC Davis MIND Institute, University of Denver, Northwestern University, Rush University, and University of California, Riverside, have updated and validated a series of tests within the NIH Toolbox (NIHTB) to assess cognition in people with intellectual disability. The validation of the NIH Toolbox in individuals with intellectual disabilities opens new opportunities for better, more accurate results in a population that is exceedingly difficult to evaluate.

Led by David Hessl, the study team enrolled 242 individuals with Fragile X syndrome (FXS), Down syndrome (DS), and other intellectual and developmental disabilities, ages six through 25 years, and retested after one month. The study team adapted the NIH Toolbox battery by developing accommodations and standard assessment guidelines documented in an e-manual. The researchers determined that all seven tests of the adapted NIH Toolbox could accurately measure cognitive skills in individuals with a mental age of five or above. In individuals with a mental age below five, there was more variability. Some of the tests performed very well, and others need more research and additional modifications before the NIH Toolbox can be equally good at measuring skills in these individuals who are lower functioning.

This test is quick (one hour or less!), feasible for most, and participants were willing and able to respond to the test questions. The test measures a variety of skills, including memory, expressive (what is said) and receptive (what is understood) vocabulary, single-word reading and processing speed, executive functioning (the ability to shift from one thought to another or to pay attention and inhibit impulses), and cognitive flexibility (asking the participant to complete the task one way, then changing the rules so the participant has to complete the task differently). The adapted NIH Toolbox battery found to be reliable; the scores were consistent after retesting individuals.

Why This Matters

It can be challenging to capture an individual’s true ability with a cognitive test. Adapting a cognitive battery to better capture changes in individuals with intellectual and developmental disabilities will help researchers better understand if cognitive changes are occurring in a reliable, objective way. The NIH Toolbox has already been used as an outcome measure for clinical trials in Fragile X like the metformin trial at UC Davis. Adopting the NIH Toolbox as a standard cognitive battery will help the field move forward, making results easier to compare across studies. There is also a clinical promise to use the NIH Toolbox.

Next Steps

More research is needed to validate the complete NIH Toolbox in individuals with a mental age of less than five years old. Continued research into the sensitivity of the NIH Toolbox to development/treatment changes is needed.

Funding for the study came from the NICHD (RO1HD076189), the Health and Human Services Administration of Developmental Disabilities (90DD0596), the MIND Institute Intellectual and Developmental Disabilities Research Center (U54 HD079125), and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1 TR000002.

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The Impact of the COVID-19 Pandemic on School-Aged Children with Fragile X Syndrome

The pandemic caused by the spread of the coronavirus disease (COVID-19), beginning in early 2020, had an impact beyond anything experienced in recent history. It is important to understand how this pandemic era has impacted school-aged children with FXS so that we may continue to successfully navigate the changes that come with living through a pandemic and to understand what we can improve in the case of a future pandemic.