A Cognitive Test Battery for Intellectual Disabilities

 描述(由申请人提供)：有一个快速增长的翻译研究努力，以了解神经发育障碍的大脑机制，如脆性X综合征(FXS)、唐氏综合症(DS)和其他导致智力残疾的疾病(ID)。来自这些症状形式残疾的动物模型的证据表明，靶向治疗具有很强的潜力，可以使与这些疾病相关的人类神经生物学、行为，或许还有认知异常正常化。这项开创性的工作已经导致许多对照临床试验已经在进行中，还有更多的试验现在处于规划阶段。然而，对于ID患者来说，几乎没有适合发展的、经过充分验证的、敏感和可靠的适合于跟踪治疗反应的认知测量方法。事实上，可以说，缺乏这种测量方法的及时开发大大减缓了靶向治疗的翻译，并可能导致对此类试验结果的错误解释，损害针对ID综合征的靶向治疗的开发努力。为了回应这一迫切需求，拟议项目的主要目标是验证一套认知测量，包括执行功能、处理速度、情景记忆、语言和注意力，作为ID患者的结果测量，最初的主要重点是脆性X和唐氏综合症。这种认知电池最初是由NIH神经科学蓝图工具箱联盟为3至89岁的普通人群开发的，在当前的项目中，将根据需要对患有ID的人进行验证和修改。此外，在两年的时间里，对参与者的这些和其他测量方法进行纵向研究将有助于建立对变化的敏感性。这项拟议的研究将有助于广泛的研究，旨在评估或改善ID患者的特定认知领域和一般智力功能。

 DESCRIPTION (provided by applicant): There is a rapidly growing translational research effort to understand the brain mechanisms of dysfunction in neurodevelopmental disorders such as fragile X syndrome (FXS), Down syndrome (DS), and other conditions that cause intellectual disabilities (ID). Evidence from the animal models of these syndromic forms of disability documents that targeted treatments have strong potential to normalize the neurobiological, behavioral, and perhaps cognitive abnormalities associated with these conditions in humans. This groundbreaking work has led to many controlled clinical trials already underway, and many more now in the planning stages. However, virtually no developmentally appropriate, well-validated, sensitive and reliable cognitive measures suitable for tracking treatment response are available for individuals with ID. Indeed it could be argued that lack of timely development of such measures has significantly slowed translation of targeted treatments and could result in incorrect interpretation of such trial results, compromising development efforts for targeted treatments aimed at ID syndromes. In response to this urgent need, the primary aim of the proposed project is to validate a set of cognitive measures of executive function, processing speed, episodic memory, language, and attention for use as outcome measures for individuals with ID, with a primary initial focus on fragile X and Down syndromes. This cognitive battery was initially developed by the NIH Neuroscience Blueprint Toolbox consortium for the general population for ages of 3 to 89 years, and in the current project will be validated and modified as necessary for those with ID. Furthermore, a longitudinal study of these and other measures in participants over a two-year period will help to establish sensitivity to change. The proposed research will benefit a wide range of studies aiming to assess or improve specific domains of cognition and general intellectual functioning in persons with ID.