A Cognitive Test Battery for Intellectual Disabilities

智力障碍认知测试电池

• 批准号: 10480829
• 负责人: DAVID R HESSL
• 金额: $ 76.21万
• 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/10480829
• 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 Control; Placebo Effect; Placebos; Population; Predisposition; Property; Psychometrics; Randomized; Reading; Research; Research Personnel; Ritalin; Sampling; Severities; Short-Term Memory; Solid; Standardization; Stimulant; 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; maladaptive behavior; 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 智力和发展障碍的基础科学和临床前研究（IDD）具有 超过了在人类临床中测量治疗反应的工具的开发和验证 试验。而越来越多的目标治疗记录以归一化的目标治疗 动物模型中的神经生物学和行为表型用于实验性 对具有IDD的人类的评估，结果指标的局限性以及缺乏共识 研究人员一直是转化管道进步的主要障碍。实际上，已经 认为在某些所谓的“失败”中错过了实验治疗的真正好处 试验”由于对感兴趣障碍的结果指标的变化缺乏敏感性，和/或 对大型安慰剂效应的敏感性掩盖了这些潜在的实际变化。在过去的5个 几年来，我们取得了重大进展，以验证美国国立卫生研究院工具箱 认知电池（NIHTB-CB）用作IDD和IDD的个体的一组结果指标 已经产生了稳固的心理测量证据，证明了其对高比例的人的实用性 精神年龄在5年或以上。尽管有这些重要的进步，但我们的工作也突出了 批判知识差距和潜在解决方案。首先，一些已建立的NIHTB-CB测试是 不可行或缺乏可接受的心理计量学特性，对更严重的影响或非常年轻 患有IDD的人 - 仍然是干预关键目标的亚组 - 电池确实 不涵盖可以在开发早期很早就测量的重要领域。第二，杂交 可以从电池的普通样本，NIHTB-CB的纵向轨迹中获得截面数据 IDD患者之间的测试分数不可用。第三，目的地证据表明对 发展变化，目前尚无数据证明NIHTB-CB对 与治疗相关的变化。对于当前项目，我们将a）优化NIHTB-CB以较低 具有中度和重度IDD的个体功能，b）完全开发和验证 新的NIHTB-CB测试以填补当前未评估的认知结构中的关键空白，包括 概念形成和算术，c）扩展对NIHTB-的发展变化的理解 使用IDD儿童和青少年的纵向观察进行扩展的CB测试，d）检查 NIHTB-CB使用A检测与治疗相关的认知变化的初步敏感性 随机，双盲安慰剂对照刺激剂（哌醋甲酯扩展释放液体）试验 在具有IDD + ADHD的儿童和青少年中。预计成功实现了这些 知识差距将导致可扩展的标准化认知电池适合宽度 在现场使用和考虑FDA注册。