Cognitive Outcome Measures in School Age Children with Down Syndrome

项目总结 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的差距 检测唐氏综合征(DS)儿童的变化。缺乏这种结果衡量标准代表着一种 解释旨在改善DS患者生活的临床试验的重要问题。如果没有 基于证据的认知结果衡量，未来在这一人群中的治疗试验仍将是次优的 由于学习措施不力。尽管在目前推荐的评估中有一些有希望的发现 电池，DS患者认知结果测量的证据基础是有限的。多站点研究评估 成果衡量的可靠性和有效性是支持评价新的 DS儿童的药物和临床干预。NICHD召集的工作组领导 DS方面的专家提出了在这一人群中使用的有前景的措施的建议。目前的研究 建议评估推荐的有希望的措施的心理测量学特性，并扩展到 这些建议通过评估个体的可变性和核算评估的方法 (口头、非口头、计算机、家长报告)来支持我们对认知中的表现的理解 域。此应用程序的总体目标是建立临床结果的心理测量学特性 DS儿童在执行功能(抑制、工作)认知领域的测量 记忆、定势转移)、学习和记忆以及处理速度。我们从事这项工作的理由是 人群是DS与认知强弱的不同模式有关，这些认知强弱与他们的 神经解剖学。因此，选择要评价的结果衡量标准需要考虑DS 行为表型。我们提出了三个具体的目标：1)检查心理测量学特性 在对DS儿童的评估中采取的措施。2)评价心理测量学的差异 作为人口统计学和医学合并症变化的函数的测量的特性。3)至 描述认知和执行功能的发展轨迹。为了实现这些目标，160 患有DS的6-17岁儿童将参与重复的神经心理评估并进行随访 分别在2周、3个月、6个月和1年进行评估。家长和老师将完成对 执行功能、适应性行为和行为关注。我们的研究团队具有独特的优势 开展这项工作，结合DS、神经心理评估、医疗条件和 测量评估。我们预计，这项测量研究将为未来提供重要的指导 疗效和有效性试验。我们的目标与NICHD PAR-16-216研究优先顺序一致，以评估 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 目标是DS。随着我们的领域继续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400,000名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.