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

执行功能障碍作为 DS 临床试验的治疗目标：对其现实世界和神经相关性的评估。

• 批准号: 10295990
• 负责人: Nancy Raitano Lee
• 金额: $ 41.94万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295990
• 关键词: Adaptive Behaviors; Adult; Age; Behavior; Biological; Biological Markers; Brain; Brain imaging; Brain region; Characteristics; Clinical Trials; Cognition Disorders; Cognitive; Community Participation; Complex; Data; Development; Distal; Down Syndrome; Effect Modifiers (Epidemiology); Employment; Evaluation; Executive Dysfunction; Family; Funding; Future; General Population; Geographic Locations; Goals; Health; Impairment; Individual; Individual Differences; Informal Social Control; Intervention; Investigation; Knowledge; Link; Measures; Methodology; Modeling; Near-Infrared Spectroscopy; Neurobehavioral Manifestations; Neurocognitive; Neurophysiology - biologic function; Outcome; Participant; Patient-Focused Outcomes; Patients; Personal Satisfaction; Phenotype; Population; Prefrontal Cortex; Problem Solving; Process; Quality of life; Reporting; Research; Research Project Grants; Risk; Role; Sampling; Short-Term Memory; Symptoms; United States; United States National Institutes of Health; associated symptom; autism spectrum disorder; autistic; base; clinical trial readiness; cognitive control; cognitive skill; cohort; daily functioning; executive function; flexibility; functional outcomes; functional status; improved; informant; interest; neural correlate; patient stratification; psychiatric symptom; relating to nervous system; resilience; skills; symptomatology; targeted therapy trials; therapy development; trait; young adult

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.

项目摘要/摘要（项目摘要）： 正如NIH唐氏综合症（DS）的NIH研究计划中所强调的，包括项目研究计划， 有必要组装大量具有DS的人群进行研究，以检查风险和韧性 与健康和福祉相关的因素。这些研究不仅对DS的研究有影响，而且对 普通人群中的个人。拟议的研究旨在研究影响福祉的因素 在患有DS的成年人中，专注于对DS及其家人至关重要的成人结果， 即职业地位和适应性行为技巧。尽管它们的重要性，但这些远端是 旨在支持发展的临床试验研究的良好候选治疗目标 患有DS的人的结果。相反，认知技能可能是近端治疗目标，尤其是 执行功能或认知控制过程，对自我调节很重要和完成 复杂的任务。因此，拟议的研究试图评估执行功能障碍作为治疗目标 对于年轻人的DS。为了确定行政功能障碍的重要性，本研究（如果资助）将：a）检查 执行功能障碍与两个至关重要的功能结果，职业状况和 来自美国各地的DS（n = 200）的大量年轻人队列的自适应技能（带有数据 在线聚集以最大化参与者的数字和地理区域）； b）评估 自闭症特征（同时出现的症状可能对DS产生影响）的调节影响 功能障碍和这些功能结果（这不仅与DS人群有关，而且与一般性有关 受自闭症谱系障碍影响的人群）； c）链接执行功能障碍与前额叶皮质障碍 使用对患者友好的大脑成像方法的活性，用于近红外光谱（FNIRS） 在患有DS的年轻人中（n = 25）。因此，拟议的研究代表了识别的重要第一步 执行功能障碍作为临床试验治疗目标的重要性，通过建立与两者的联系 关键的远端功能结果和近端神经基础，同时还评估了潜在的 同时发生自闭症特征的信息适度影响。