Memory Measures for Clinical Trials in Down syndrome and Fragile X syndrome

唐氏综合症和脆性 X 综合症临床试验的记忆测量

• 批准号: 9155233
• 负责人: JAMIE O. EDGIN
• 金额: $ 65.19万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-22 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9155233
• 关键词: 11 year old; 3 year old; Adaptive Behaviors; Address; Adult; Age; Arizona; Assessment tool; Attention; Behavioral; Characteristics; Child; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive Therapy; Cognitive deficits; Collaborations; Consensus; Cross-Sectional Studies; Data; Development; Down Syndrome; Face; Floor; Fragile X Syndrome; Future; Heterogeneity; Hippocampus (Brain); Human; Individual; Institutes; Intellectual functioning disability; Intervention; Intervention Studies; Investigation; Language; Lead; Legal patent; Light; Maps; Measurement; Measures; Medial; Memory; Memory impairment; Methods; Mus; Neurosciences; Outcome Measure; Parents; Participant; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase; Population; Prevalence; Process; Property; Psychometrics; Reporting; Research; Site; Staging; Structure; Syndrome; System; Temporal Lobe; Testing; Theoretical model; Therapeutic; Therapeutic Agents; Treatment Efficacy; United States National Institutes of Health; Universities; Validation; Validity and Reliability; Work; age group; age related; base; clinical investigation; cognitive ability; cognitive testing; computerized; critical period; design; early childhood; mental age; mouse model; named group; neuropsychological; novel; primary outcome; programs; relating to nervous system; sound; targeted agent; therapeutic target; touchscreen; usability; working group

Project Summary Recent advances in pharmacological treatment for cognitive deficits in fragile X syndrome (FXS) and Down Syndrome (DS) have been numerous, resulting in a number of clinical trials that will soon proceed to stages of human testing in children and adults. However, treatment studies in individuals with intellectual disabilities (ID) face a number of measurement challenges, and few studies have been conducted to assess the suitability of neuropsychological measures for use in children with ID. In particular, while several pharmacological agents target the function of the hippocampus and associated memory systems, relatively little work has been completed to validate measures assessing function in this domain. Given that a number of proposed pharmacological agents target the function of the hippocampus, memory will likely be designated as a “primary” outcome in a number of upcoming trials. This makes memory test validation a critical next step in supporting pharmacological approaches to cognitive interventions in ID. Thus, in the current proposal we plan to further develop and validate a theoretically-informed, comprehensive android touch-screen memory assessment system for use in young children with ID. Across 3 sites (University of Arizona, UC Davis, Drexel University) with extensive expertise in research with ID groups, we will first establish the usability, internal consistency, and form equivalence of the measure in 30 typically developing 3 year olds (Phase 1). In Phase 2, we will test the properties in a group with DS or FXS (n = 30, age 6H18 years) after measure revision and input from consultants and PIs. In Phase 3, we will determine the psychometric properties of the memory assessment in 180 children with DS and FXS (n=90 per group). We will evaluate floor and ceiling effects, internal consistency, validity, and sensitivity to developmental change and ID group effects. To determine the validity of each measure, we will correlate each test with other assessments, including the NIH Toolbox Early Childhood Battery, IQ, adaptive behavior, and parent-reported memory. Comparisons with mental age matched controls (n = 90, ages 3 to 6 years) will determine the sensitivity of the measures to detect group differences and cross-sectional age-related change during a critical period of memory development. The DS and FXS children will be re-assessed at 4 and 24 weeks to assess measurement retest- reliability and stability. As effective measures are required across a wide age range and in individuals with differing background characteristics, we will test how each measure’s psychometric properties may vary based on age and participant’s level of attention. We hope to better understand which subject characteristics might lead to inconsistent performance and define which measures may be effective across the majority of children with these syndromes. Through this work, we will provide evidence to help determine which measures may be strong primary outcomes for clinical trials in DS and FXS. The results of this investigation will provide a methodological advance that will set the field forward toward more consistent and valid assessment of this important domain for intervention studies of drug therapies as well as in behavioral cognitive interventions.

项目摘要 脆弱X综合征（FXS）和唐氏综合症（DS）的认知缺陷药物治疗的最新进展已有很多，导致了许多临床试验，这些试验将很快继续进行儿童和成人的人类测试阶段。但是，对智障人士（ID）的治疗研究面临许多测量挑战，并且很少进行研究以评估神经心理学测量的适用性，用于使用ID的儿童。特别是，虽然几种药理学剂针对海马和相关的记忆系统的功能，但几乎没有完成以验证该域中的测量评估功能的工作。鉴于许多提出的药理剂针对海马的功能，因此在许多即将进行的试验中，记忆可能被指定为“主要”结果。这使得内存测试验证成为支持ID认知干预措施的药物方法的关键下一步。在当前的提案中，我们计划进一步开发和验证理论知识的，全面的Android触摸屏记忆评估系统，以用于ID的幼儿。在3个地点（亚利桑那大学，加州大学戴克斯郡分校，德雷克塞尔大学）具有广泛的ID研究专业知识，我们将首先建立第2阶段测量的可用性，内部一致性和形式的等效性，我们将测试DS或FXS（n = 30，年龄6H18岁，年龄在6H18岁）咨询和咨询咨询和咨询咨询和咨询和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS和PIS的属性。在第3阶段，我们将确定180名DS和FXS儿童（每组n = 90）的记忆评估的心理测量特性。我们将评估地板和天花板效应，内部一致性，有效性以及对发展和ID组效应的敏感性。为了确定每种度量的有效性，我们将将每个测试与其他评估相关联，包括NIH工具箱幼儿电池，智商，自适应行为和父母报告的记忆。与心理年龄匹配的对照组的比较（n = 90，3至6岁）将决定在记忆发展的关键时期内检测群体差异和横截面年龄相关的变化的敏感性。 DS和FXS儿童将在4周和24周重新评估，以评估测量重测和稳定性。由于在广泛的年龄范围内需要采取有效的措施，并且在具有不同背景特征的个体中，我们将测试每个措施的心理测量特性如何根据年龄和参与者的关注水平而变化。我们希望更好地理解哪些主题特征可能会导致不一致的表现，并定义哪些措施在大多数这些综合症的儿童中可能有效。通过这项工作，我们将提供证据，以帮助确定哪些措施可能是DS和FXS临床试验的强大主要结果。这项调查的结果将提供一种方法上的进步，该进步将使该领域朝着对药物疗法以及行为认知干预措施进行干预研究的这一重要领域进行更一致和有效的评估。