Recent advances in pharmacological treatment for cognitive deficits in fragile X syndrome (FXS) and Down Syndrome (DS) have been numerous, resulting in of active and planned clinical trials for cognitive enhancement. Given that a number of proposed pharmacological agents for ID groups target the function of the hippocampus, memory will likely be designated as a ?primary? outcome in upcoming trials. However, relatively little work has been completed to validate measures assessing function in this domain. In a funded RO1, our group is further developing and validating a theoretically-informed, comprehensive android touch-screen memory assessment system for use in young children with ID. Across three sites (University of Arizona, UC Davis, Drexel University) with extensive expertise in research with ID groups, we are establishing the validity of the measure with a design which mirrors the administration of measures in a clinical trial. Thus, in this Revision proposal, we plan to expand data collection on a funded RO1 in two key ways. First, the profile of sleep deficits and its impact on clinical trial outcomes in these groups has not been previously examined. Therefore, we will include objective (actigraphy) and caregiver-reported assessments of sleep, assess the reliability of sleep assessments, determine the profile of sleep deficits in relation to chronological age (CA) matched controls, relate these outcomes to memory outcomes, and determine the relation of these measures to test stability. Through this work, we will provide evidence to help determine which measures may be strong primary outcomes for clinical trials in DS and FXS and the extent that sleep may be measured and influential in clinical trials. The results of this investigation will provide a methodological advance allowing for more consistent and valid assessment of memory function for intervention studies of drug therapies and behavioral cognitive interventions. Second, our funded work includes children with DS and FXS 6-18 years of age, a key developmental period for the validation of outcome assessments for clinical trials, as many recent trials have targeted this age-range. However, the funded RO1 did not include CA-matched controls, and it is necessary for us to expand data collection to include 90 CA-matched children. This expansion will help establish how sensitive these measures are to detect expected changes in older children without ID- an important metric for determining their utility across a range of ages and ID syndromes. Older children will provide essential information regarding how the stability of memory outcomes could differ after 12 years. In particular, it is known that sleep is poorer in older children (>12 years) due to biological and social changes, which could have an impact on the reliability of outcomes in a clinical trial. In total, this application proposes revisions that are necessary to fully inform future clinical trials in these and other ID syndromes.
In order to advance clinical trials of cognitive interventions in Intellectual Disabilities (ID), including Down syndrome and fragile X syndrome, validated cognitive outcome measures are urgently required. Given that a number of therapeutic agents are focused on increasing memory function in ID, we are engaged in the development and validation of a novel computerized memory assessment to provide more valid, reliable, and developmentally appropriate measures for these trials. This revision application aims to add sleep assessment and appropriate controls to this outcome measurement validation work; the findings from this study expansion could inform future clinical trials across a range of ID syndromes.
| Sakhon, Stella; Edwards, Kelly; Luongo, Alison et al. (2018) Small Sets of Novel Words Are Fully Retained After 1-Week in Typically Developing Children and Down Syndrome: A Fast Mapping Study. J Int Neuropsychol Soc 24:955-965 |
| Edgin, Jamie O; Anand, Payal; Rosser, Tracie et al. (2017) The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects. Am J Intellect Dev Disabil 122:215-234 |
| Clark, Caron A C; Fernandez, Fabian; Sakhon, Stella et al. (2017) The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise. Hippocampus 27:683-691 |
