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) 研究计划和 INCLUDE 项目研究计划所强调的那样， 需要聚集大量 DS 患者进行研究来检查风险和恢复力 与健康和福祉相关的因素。这些研究不仅对 DS 患者有影响，而且对 一般人群中的个人。拟议的研究旨在研究影响幸福感的因素 通过关注对 DS 患者及其家人重要的成人结局， 即职业地位和适应性行为技能。尽管它们很重要，但这些远端结果 不太可能成为旨在支持发育的临床试验研究的良好候选治疗目标 DS 患者的结果。相反，认知技能可能是良好的近期治疗目标，特别是 对于自我调节和完成任务很重要的执行功能或认知控制过程 复杂的任务。因此，拟议的研究旨在评估执行功能障碍作为治疗目标 用于年轻人的 DS。为了确定执行功能障碍的重要性，本研究如果获得资助，将：a）检查 执行功能障碍与两个至关重要的功能结果（职业地位和职业地位）之间的联系 来自美国各地的一大群患有 DS 的年轻人 (n=200) 的适应技能（数据 在线收集，以最大限度地提高参与者数量和所代表的地理区域）； b) 评估 调节自闭症特征（可能对 DS 产生影响的同时出现的症状）对执行能力的影响 功能障碍和这些功能结果（这不仅与 DS 人群相关，而且与一般人群相关） 受自闭症谱系障碍影响的人群）； c）将执行功能障碍与前额皮质联系起来 使用功能性近红外光谱 (fNIRS) 的患者友好型大脑成像方法进行活动 患有 DS 的年轻人 (n=25)。因此，拟议的研究代表了识别 通过建立执行功能障碍与两者的联系，强调执行功能障碍作为临床试验治疗目标的重要性 关键的远端功能结果和近端神经基础，同时还评估潜在的 同时发生的自闭症特征的信息调节影响。