There is a rapidly growing translational research effort to understand the brain mechanisms of dysfunction in neurodevelopmental disorders such as fragile X syndrome (FXS), Down syndrome (DS), and other conditions that cause intellectual disabilities (ID). Evidence from the animal models of these syndromic forms of disability documents that targeted treatments have strong potential to normalize the neurobiological, behavioral, and perhaps cognitive abnormalities associated with these conditions in humans. This groundbreaking work has led to many controlled clinical trials already underway, and many more now in the planning stages. However, virtually no developmentally appropriate, well-validated, sensitive and reliable cognitive measures suitable for tracking treatment response are available for individuals with ID. Indeed it could be argued that lack of timely development of such measures has significantly slowed translation of targeted treatments and could result in incorrect interpretation of such trial results, compromising development efforts for targeted treatments aimed at ID syndromes. In response to this urgent need, the primary aim of the proposed project is to validate a set of cognitive measures of executive function, processing speed, episodic memory, language, and attention for use as outcome measures for individuals with ID, with a primary initial focus on fragile X and Down syndromes. This cognitive battery was initially developed by the NIH Neuroscience Blueprint Toolbox consortium for the general population for ages of 3 to 89 years, and in the current project will be validated and modified as necessary for those with ID. Furthermore, a longitudinal study of these and other measures in participants over a two-year period will help to establish sensitivity to change. The proposed research will benefit a wide range of studies aiming to assess or improve specific domains of cognition and general intellectual functioning in persons with ID.
Recent advances in the understanding of the neurobiology of fragile X syndrome, Down syndrome and other intellectual disabilities have given rise to targeted treatments now under study in a growing number of clinical trials. The aim of this project is to develop and validate a cognitive battery for intellectual disabilities so that investigators will have a sensitive and developmentally appropriate set of tools for tracking improvement in key domains such as attention, memory, and processing speed in the context of these treatment studies.
| Thompson, Talia; Coleman, Jeanine M; Riley, Karen et al. (2018) Standardized Assessment Accommodations for Individuals with Intellectual Disability. Contemp Sch Psychol 22:443-457 |
| Berry-Kravis, Elizabeth; Chin, Jamie; Hoffmann, Anne et al. (2018) Long-Term Treatment of Niemann-Pick Type C1 Disease With Intrathecal 2-Hydroxypropyl-?-Cyclodextrin. Pediatr Neurol 80:24-34 |
| Hessl, David; Sansone, Stephanie M; Berry-Kravis, Elizabeth et al. (2016) The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions. J Neurodev Disord 8:35 |
