Cognitive Outcome Measures in School Age Children with Down Syndrome

项目摘要 在可靠和敏感的认知结果测量方法的可用性方面存在根本性差距， 检测唐氏综合征（DS）儿童的变化。缺乏这种成果衡量标准， 这是解释旨在改善DS患者生活的临床试验的重要问题。没有 基于证据的认知结果测量，未来在这一人群中的治疗试验仍将是次优的 由于学习成绩差。尽管目前建议的评估中有一些令人鼓舞的结果， 电池，证据基础的认知结果的措施，在DS是有限的。多中心研究评价 结果测量的可靠性和有效性是支持新的评价所需的下一步。 药物和临床干预与DS儿童。国家排雷中心召集的工作组 DS的专家们提出了在这一人群中使用的有希望的措施的建议。目前的研究 建议评估推荐的有前途的措施的心理测量特性，并扩大 这些建议通过评估个体变异性和评估方法的解释 （口头的，非口头的，计算机，父母报告），以支持我们的认知范围内的性能的理解 域本申请的总体目标是建立临床结果的心理测量学特性 在执行功能的认知领域（抑制，工作）与DS儿童的措施 记忆，集合移位），学习和记忆，以及处理速度。我们的工作原理是 DS与一种独特的认知优势和弱点模式相关， 神经解剖学因此，选择要评价的结局指标需要考虑DS 行为表型我们提出了三个具体的目标：1）检查的心理测量学特性， 在与DS儿童的评估电池的措施。2)为了评估心理测量的差异， 作为人口统计学和医学合并症的变化的函数的测量的性质。3)到 描述认知和执行功能的发展轨迹。为了实现这些目标，160 6-17岁的DS儿童将参加重复的神经心理学评估， 在2周、3个月、6个月和1年时进行评价。家长和老师将完成对 执行功能、适应行为和行为问题。我们的研究团队具有独特的优势， 进行这项工作，结合DS，神经心理学评估，医疗条件和 测量评价我们预计，这项测量研究将为未来的研究提供重要的指导。 功效和有效性试验。我们的目标符合NICHD PAR-16-216研究优先级，以评估 在ID临床试验中使用的措施的可靠性，有效性和随时间的变化，在这种情况下，特别是 针对DS。随着我们的领域不断开发新的药物和临床干预措施，我们的项目将 支持这项工作，并对生活在美国的40万DS患者产生影响。

PROJECT SUMMARY There is a fundamental gap in the availability of cognitive outcome measures that are reliable and sensitive to detecting change among children with Down syndrome (DS). Lack of such outcome measures represents an important problem to interpreting clinical trials aimed at improving the lives of individuals with DS. Without evidence-based cognitive outcome measures, future treatment trials in this population will remain suboptimal due to poor study measures. Despite some promising findings in currently recommended assessment batteries, the evidence base for cognitive outcome measures in DS is limited. Multi-site studies evaluating the reliability and validity of outcome measures are the needed next step towards supporting the evaluation of new pharmaceutical and clinical interventions for children with DS. Working groups convened by NICHD of leading experts in DS led to recommendations of promising measures for use in this population. The current study proposes to evaluate the psychometric properties of recommended promising measures and expands upon these recommendations by evaluating individual variability and accounting for the method of assessment (verbal, nonverbal, computer, parent-report) to support our understanding of performance within a cognitive domain. The overall objective of this application is to establish the psychometric properties of clinical outcome measures in children with DS across the cognitive domains of executive functioning (inhibition, working memory, set-shifting), learning and memory, and processing speed. Our rationale for working with this population is that DS is associated with a distinct pattern of cognitive strengths and weaknesses related to their neuroanatomy. Thus the selection of outcome measures to be evaluated needs to take into account the DS behavioral phenotype. We propose three specific aims: 1) To examine the psychometric properties of measures in the assessment battery with children with DS. 2) To evaluate differences in the psychometric properties of the measures as a function of variations in demographics and medical comorbidities. 3) To characterize the developmental trajectories of cognition and executive functioning. To achieve these aims, 160 children ages 6-17 years with DS will participate in repeated neuropsychological assessments with follow-up evaluations at 2 weeks, 3 months, 6 months, and 1 year. Parents and teachers will complete ratings of executive functioning, adaptive behavior and behavioral concerns. Our research team is uniquely positioned to conduct this work, combining expertise in DS, neuropsychological assessment, medical conditions and measurement evaluation. We anticipate that this measurement study will provide critical guidance for future efficacy and effectiveness trials. Our goals are in line with NICHD PAR-16-216 research priority to assess the reliability, validity and change over time of measures for use in clinical trials in ID, in this case specifically targeted to DS. As our field continues to develop new pharmaceutical and clinical interventions, our project will support this work and have an impact on the 400,000 individuals with DS living in the United States.