Executive dysfunction as a treatment target for DS clinical trials: An evaluation of its real-world and neural correlates.

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Project Summary/Abstract (Project Summary): As highlighted in the NIH Research Plan on Down Syndrome (DS) and the INCLUDE Project Research Plan, there is a need to assemble large cohorts of individuals with DS for studies that examine risk and resilience factors relevant to health and well-being. These studies have implications not only for those with DS but for individuals in the general population. The proposed research aims to examine factors which impact well-being in adults with DS by focusing on adult outcomes that are important to individuals with DS and their families, namely vocational status and adaptive behavior skills. In spite of their importance, these distal outcomes are unlikely to be good candidate treatment targets for clinical trials research that aims to support developmental outcomes in individuals with DS. Instead, cognitive skills are likely good proximal treatment targets, particularly executive function or cognitive control processes that are important for self-regulation and the completion of complex tasks. Therefore, the proposed research seeks to evaluate executive dysfunction as a treatment target for DS in young adults. To establish the importance of executive dysfunction, this study, if funded, will: a) examine links between executive dysfunction and two critically important functional outcomes, vocational status and adaptive skills in a large cohort of young adults with DS (n=200) from across the United States (with data gathered online to maximize participant numbers and geographic regions represented); b) evaluate the moderating influence of autistic traits (co-occurring symptoms likely to have impacts in DS) on executive dysfunction and these functional outcomes (which is relevant not only to the DS population but also the general population impacted by autism spectrum disorder); and c) link executive dysfunction with prefrontal cortical activity using the patient-friendly brain imaging methodology of functional near infrared spectroscopy (fNIRS) among young adults with DS (n=25). Thus, the proposed research represents an important first step in identifying the importance of executive dysfunction as a clinical trials treatment target through establishing its links with both critical distal functional outcomes and proximal neural underpinnings, while also evaluating the potentially informative moderating influence of co-occurring autistic traits.