A Cognitive Test Battery for Intellectual Disabilities

智力障碍认知测试电池

• 批准号: 10265593
• 负责人: DAVID R HESSL
• 金额: $ 76.72万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2025-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10265593
• 关键词: Adaptive Behaviors; Adolescent; Affect; Age; Animal Model; Attention; Attention deficit hyperactivity disorder; Basic Science; Behavior; Child; Clinical Trials; Cognition; Cognitive; Concept Formation; Consensus; Crystallization; Data; Development; Disease; Double-Blind Method; Down Syndrome; Episodic memory; Evaluation; Executive Dysfunction; Floor; Fragile X Syndrome; Goals; Growth; Human; Individual; Infant; Intellectual functioning disability; Intervention; Knowledge; Language; Language Disorders; Liquid substance; Measurement; Measures; Memory; Natural History; Neurobiology; Observational Study; Outcome; Outcome Measure; Patients; Performance; Persons; Pharmaceutical Preparations; Phenotype; Placebo Effect; Placebos; Population; Predisposition; Property; Psychometrics; Randomized; Reading; Research; Research Personnel; Ritalin; Sampling; Severities; Short-Term Memory; Solid; Standardization; Subgroup; Syndrome; Testing; Time; Toddler; United States National Institutes of Health; Validation; Vocabulary; Work; autism spectrum disorder; base; behavioral phenotyping; clinical outcome measures; cognitive change; cognitive testing; comparative; executive function; feasibility testing; flexibility; improved; interest; intervention effect; mathematical ability; mental age; population based; preclinical study; primary outcome; processing speed; tool; translational pipeline; treatment response

Abstract The basic science and preclinical studies of intellectual and developmental disabilities (IDDs) have outpaced the development and validation of tools to measure treatment response in human clinical trials. While an ever-increasing number of targeted treatments documented to normalize neurobiological and behavioral phenotypes in animal models are advanced for experimental evaluation in humans with IDDs, limitations of outcome measures and lack of consensus among investigators have been major barriers to progress in the translational pipeline. In fact, it has been argued that true benefits of experimental treatments have been missed in some so-called “failed trials” due to lack of sensitivity to change in the outcome measures for the disorder of interest, and/or susceptibility to large placebo effects that obscure these potentially real changes. For the past 5 years we have made substantial progress validating the National Institutes of Health Toolbox Cognitive Battery (NIHTB-CB) for use as a set of outcome measures for individuals with IDDs and have generated solid psychometric evidence of its utility for a high proportion of individuals with mental ages at or above 5 years. Despite these important advances, our work has also highlighted critical knowledge gaps, and potential solutions. First, some of the established NIHTB-CB tests were not feasible or lacked acceptable psychometric properties for more severely affected or very young individuals with IDD – subgroups that remain critical targets for intervention – and the battery does not cover important domains which can be measured very early in development. Second, while cross- sectional data is available from the battery’s normative sample, longitudinal trajectories of NIHTB-CB test scores among people with IDD are not available. And third, despite evidence of sensitivity to developmental changes, there are currently no data to demonstrate that the NIHTB-CB is sensitive to treatment-related change. For the current project we will a) optimize the NIHTB-CB for lower functioning individuals with moderate and severe IDD, b) complete development and validation of new NIHTB-CB tests to fill critical gaps in cognitive constructs not currently assessed, including Concept Formation and Numeracy, c) extend understanding of developmental changes in the NIHTB- CB tests using expanded longitudinal observations in children and youth with IDD, and d) examine the preliminary sensitivity of the NIHTB-CB to detect treatment-related cognitive changes utilizing a randomized, double-blind placebo-controlled stimulant (methylphenidate extended release liquid) trial in children and adolescents with IDD + ADHD. It is anticipated that successful fulfillment of these knowledge gaps will result in a scalable and standardized cognitive battery suitable for widespread use in the field and consideration for FDA registration.

抽象的 智力和发育障碍（IDD）的基础科学和临床前研究 超过了测量人类临床治疗反应的工具的开发和验证 试验。尽管有越来越多的靶向治疗被证明可以使病情正常化 动物模型中的神经生物学和行为表型已用于实验 对 IDD 患者的评估、结果测量的局限性以及缺乏共识 研究人员一直是转化管道取得进展的主要障碍。事实上，已经 认为在一些所谓的“失败的治疗”中，实验性治疗的真正好处被忽视了。 试验”，因为对感兴趣的疾病的结果测量的变化缺乏敏感性，和/或 对大量安慰剂效应的敏感性，掩盖了这些潜在的真实变化。对于过去 5 多年来我们在验证美国国立卫生研究院工具箱方面取得了实质性进展 认知电池（NIHTB-CB）用作 IDD 和 已经产生了可靠的心理测量证据，证明它对大部分患有此病的人有用 心理年龄在5岁或以上。尽管取得了这些重要进展，我们的工作也凸显了 关键知识差距和潜在的解决方案。首先，一些已建立的 NIHTB-CB 测试 对于受影响较严重或非常年幼的人来说不可行或缺乏可接受的心理测量特性 患有 IDD 的个体（仍然是干预的关键目标的亚群体）和电池确实如此 不涵盖可以在开发早期进行测量的重要领域。其次，在交叉的同时 截面数据可从电池的标准样品、NIHTB-CB 的纵向轨迹中获得 无法获得 IDD 患者的测试分数。第三，尽管有证据表明对 发育变化，目前没有数据表明 NIHTB-CB 对 治疗相关的改变。对于当前项目，我们将 a) 优化 NIHTB-CB，以降低 患有中度和重度 IDD 的功能正常的个体，b) 完整开发和验证 新的 NIHTB-CB 测试旨在填补目前尚未评估的认知结构的关键空白，包括 概念形成和计算能力，c) 扩展对 NIHTB 发展变化的理解- 使用对患有 IDD 的儿童和青少年进行扩展纵向观察进行 CB 测试，以及 d) 检查 NIHTB-CB 利用 a 检测与治疗相关的认知变化的初步敏感性 随机、双盲安慰剂对照兴奋剂（哌甲酯缓释液）试验 患有 IDD + ADHD 的儿童和青少年。预计这些成果将顺利实现 知识差距将导致可扩展和标准化的认知电池适合广泛的 现场使用以及 FDA 注册的考虑。