Introduction to the Special Issue on the Development of People With Down Syndrome Throughout the Lifespan (Part 1).

03Original abstract

Down syndrome was identified over 150 years ago and its genetic basis identified almost 60 years ago (Down, 1887; Lejeune, Turpin, & Gautier, 1959). This phenotyping and genotyping led to advances in describing the behavioral and cognitive phenotype of individuals with Down syndrome, identifying comorbid medical conditions, and improving health care and life expectancy for this population. Down syndrome mouse models (special strands of mice used to study human conditions) have been developed and have led to the improved understanding of the neuroanatomy and neuropathology present in this genetic syndrome (Das & Reeves, 2011). These advances in basic science with Down syndrome mouse models have further led to the development of pharmaceutical options targeting neurotransmitter and neurochemical targets. Based on these advances, clinical trials have evaluated existing pharmaceutical compounds with humans with Down syndrome and the first drug was developed specifically with the intention to target cognitive impairment in individuals with Down syndrome. Thus, new behavioral and pharmaceutical treatments continue to be developed for people with Down syndrome.Unfortunately, these clinical trials have not yet met with success. Existing pharmaceutical compounds demonstrated efficacy in some people with Down syndrome, but phenotypic variability in this population has led to inconsistent findings (Kishnani et al., 2010; Kishnani et al., 2009). Newly developed compounds have demonstrated improvements in targeted outcome measures that were comparable to that of the placebo group. Contributing to challenges in these clinical trials is that critical gaps remain in our knowledge base regarding the behavioral phenotype associated with Down syndrome across the lifespan. In order to generate effective treatments, and to quantify treatment outcomes in Down syndrome, rigorous descriptive work is needed to further characterize developmental profiles and trajectories in this population.To address this need, the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) coordinated working groups to evaluate the current state of the research on outcome measures for clinical trials in Down syndrome. NICHD brought together leading clinicians and basic and behavioral scientists in Down syndrome research, experts in clinical trials and measurement development, representatives from Down syndrome advocacy groups (including the National Down Syndrome Society, National Down Syndrome Congress, LuMind Research Down Syndrome Foundation, Global Down Syndrome Foundation), the FDA, and pharmaceutical companies (Roche, Janssen). The need for a special issue characterizing the Down syndrome behavioral phenotype and advances in measurement of clinical outcomes was identified at this NICHD meeting. In our call for submissions for the special issue, we stated a focus “on manuscripts that contribute to our current understanding of cognition, language and communication, self-regulation, and social-emotional functioning in Down syndrome across the lifespan, from early childhood through to older adulthood.” We gave priority to manuscripts that described longitudinal or cross-sectional descriptive work in specific areas that will inform treatment or clinical outcome research, and that described the evaluation of innovative measures targeting the Down syndrome phenotype and associated developmental outcomes.We were very fortunate to receive high quality submissions resulting in the need to spread the special issue over two parts. The current issue includes articles focused on cognition and executive functioning. These articles highlight the need for sound psychometric evaluation of outcome measures assessing these constructs, and the impact of longitudinal work on highlighting targets for intervention. The next issue will include articles focused on language, communication, and academic skills.Evaluating the psychometric properties of outcome measures is a critical component for ensuring the sound and accurate measurement of outcomes and for supporting future clinical trials. The article by Edgin et al., “The Arizona Cognitive Test Battery for Down Syndrome: Test-retest Reliability and Practice Effects,” reports on the results of a multisite evaluation of measures targeting neurocognitive function in children and adolescents with Down syndrome. Their findings help refine what measures are recommended for use in the Arizona Cognitive Test Battery. Computerized measures of working memory and hippocampal memory were demonstrated to be reliable. Gaps were identified for constructs in need of sound measurement. This work highlights the value of collaborations across basic and behavioral scientists, so that outcome measures are developed to support the outcomes targeted in mouse model research.Longitudinal designs are essential for understanding developmental profiles and trajectories as people with Down syndrome grow older. Gilmore and Cuskelly's article, “Associations of Child and Adolescent Mastery Motivation and Self-Regulation with Adult Outcomes: A Longitudinal Study of Individuals with Down Syndrome,” documents the adult outcomes of childhood and adolescent mastery motivation and self-regulation. Their powerful findings indicate that mastery motivation in early childhood predicted adaptive behavior skills in adulthood 20 years later. Their findings have implications highlighting the importance of early intervention and the cascading effects of intervening early. Their findings also suggest targets for supporting adult adaptive behavior, specifically targeting supports for children's persistence with challenging tasks.In addition to identifying a need for this special issue, the working groups convened by NICHD to evaluate outcome measures for clinical trials in Down syndrome also compiled recommendations on the state of currently available measures. The article by Esbensen et al., “Outcome Measures for Clinical Trials in Down Syndrome,” summarizes the recommendations of working groups targeting cognitive and behavioral outcome measures. The working groups identified measures by construct that currently are appropriate for clinical trials in Down syndrome, measures that may be promising with further evaluation or adaptation, and constructs where new measures need to be developed. The working group also summarized general observations regarding the ongoing need for development, validation and use of outcome measures for individuals with Down syndrome.We are sincerely thankful to Deborah Fidler, editor of AJIDD, for her passionate support of this special issue. We are especially thankful to Christopher Lemons, associate editor at AJIDD, for taking on editorial decisions on the manuscript whose authors included Deborah Fidler and myself, to avoid conflicts of interest. We are very appreciative of the support from the editorial team at AJIDD (Kathleen McLane and Michael Winfield), and the editorial assistant for AJIDD (Elizabeth Will). Finally, we also want to thank all the reviewers who graciously gave their time and helpful feedback that helped improve the submitted manuscripts.

American journal on intellectual and developmental disabilities, 2017 · doi:10.1352/1944-7558-122.3.213