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

项目摘要/摘要(项目摘要)： 正如美国国立卫生研究院唐氏综合症研究计划(DS)和包括项目研究计划中强调的那样， 有必要召集大量患有DS的人进行研究，以检查风险和弹性 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。这项拟议的研究旨在检查影响幸福感的因素。 在患有DS的成年人中，通过关注对患有DS的个人及其家庭重要的成人结果， 即职业地位和适应行为技能。尽管它们很重要，但这些远端结果是 不太可能成为旨在支持发展的临床试验研究的良好候选治疗目标 DS患者的预后。相反，认知技能可能是很好的近距离治疗目标，尤其是 执行功能或认知控制过程，对自我调节和完成 复杂的任务。因此，这项拟议的研究试图评估执行功能障碍作为治疗目标 对于年轻人中的DS。为了确定执行功能障碍的重要性，这项研究，如果得到资助，将：a)检查 执行功能障碍与两个至关重要的功能结果之间的联系，职业地位和 来自美国各地的一大批患有DS(n=200)的年轻人的适应技能(有数据 在线收集以最大化参与者数量和所代表的地理区域)；b)评估 自闭症特征(可能对DS有影响的共生症状)对执行力的缓和影响 功能障碍和这些功能结果(这不仅与DS人群有关，而且与一般人有关 受自闭症谱系障碍影响的人群)；以及c)将执行功能障碍与前额叶皮质联系起来 使用患者友好的功能近红外光谱(FNIRS)脑成像方法进行活动 青壮年DS患者(n=25)。因此，拟议的研究是确定 执行功能障碍作为临床试验治疗靶点的重要性 关键的远端功能结果和近端神经基础，同时也评估潜在的 共现自闭症特征的信息性调节影响。

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.