A Cognitive Test Battery for Intellectual Disabilities

摘要 这个R01项目(“智力障碍认知测试组合”)的总体目标是开发 并验证评估组合，以衡量智力和智力障碍患者的认知结果 临床试验中的发育障碍(IDD)。为了实现这一目标，在过去的7年里，我们一直在 汇编数据，为这一独特且具有挑战性的人群做出适当的安排，以及 仔细检查心理测量学特性(包括可行性、可靠性、效度和敏感度 NIH工具箱认知电池(NIHTB-CB)，这是一套基于iPad和常模参考的测试 测量流体推理(加工速度、工作记忆、情景记忆、抑制控制和 注意力和认知灵活性)和结晶语言(接受性词汇和阅读) 和患有IDD的青年，包括脆性X综合征(FXS)、唐氏综合征(DS)、自闭症和 特发性/其他IDDS。本行政补编申请的目的是请求 将数据收集扩展到患有IDD的老年人的额外资金，包括DS和FXS。IDDS中的老龄化 研究不足，老年人经常被排除在研究之外，部分原因是可获得的数据有限 评估工具。补充资料将允许收集NIHTB-CB数据、标准化智商和自适应 来自ABC-Down综合征联盟协调核心的100名成年人的行为数据和测量 参与者(患有DS的50人，FXS的50人；年龄在26岁及以上，在年轻人和老年人中分层) 作为血液样本，与ABC-DS小组合作进行生物标记物表征。根据ABC- DC痴呆症评估，我们计划纳入20名痴呆症患者，让他们检查潜在的敏感度 NIHTB-CB对痴呆症相关认知改变的影响。我们对成年人的扩展数据收集将主要落在 在项目目标1和3的范围内，重点是为功能较低的人优化电池 以及电池对发育变化的敏感性。特别是，我们将审查新收集的数据 以确定是否需要修改，是否需要进行新的测试 以及它是否显示出检测与衰老有关的认知恶化或 神经变性，就像一些患有DS的参与者一样。因为DS中的衰老与早期高血压的高风险相关 随着阿尔茨海默病(AD)的发展，开发和验证认知测试非常重要，这些测试可用于 跟踪疾病进程和对干预措施的反应。老年性痴呆患者的认知和神经退行性变 尽管有证据表明AD相关的生物标记物异常和认知能力下降，但FXS在很大程度上被忽视了 在一些病人身上。从FXS队列收集的补充数据将有助于确定更大的、 更广泛的纵向研究是合理的，以描述这一群体的自然历史，并打开 为他们参与其他研究打开了大门。从该老年组收集的补充NIHTB-CB数据 将提供有关其在未来自然历史或治疗研究中的潜在用途的关键初步信息。

Abstract The overarching goal of this R01 project (“A Cognitive Test Battery for Intellectual Disabilities”) is to develop and validate an assessment battery to measure cognitive outcomes of individuals with intellectual and developmental disability (IDD) in clinical trials. To achieve this goal, over the past 7 years we have been compiling data, making appropriate accommodations for this unique and challenging-to-test population, and carefully examining the psychometric properties (including feasibility, reliability, validity, and sensitivity to change) of the NIH Toolbox Cognitive Battery (NIHTB-CB), an iPad-based and norm-referenced set of tests measuring Fluid Reasoning (Processing Speed, Working Memory, Episodic Memory, Inhibitory Control and Attention, and Cognitive Flexibility) and Crystallized Language (Receptive Vocabulary and Reading) in children and youth with IDD, including those with fragile X syndrome (FXS), Down syndrome (DS), autism and idiopathic/other IDDs. The purpose of the present Administrative Supplement application is to request additional funds to extend data collection to older adults with IDD, including DS and FXS. Aging in IDDs is understudied, and older individuals are often excluded from research in part due to limitations in available assessment tools. The supplement will allow collection of NIHTB-CB data, standardized IQ and adaptive behavior data and measures from the ABC-Down Syndrome consortium harmonized core from 100 adult participants (50 with DS, 50 with FXS; ages 26 and up, stratified across young and older adult groups), as well as blood samples for biomarker characterization in collaboration with the ABC-DS group. Based upon the ABC- DC dementia assessment, we plan to include 20 with dementia to allow examination the potential sensitivity of the NIHTB-CB to dementia-related cognitive changes. Our extended data collection with adults will fall primarily within the scope of project Aims 1 and 3, which focus on optimization of the battery for lower functioning persons and sensitivity of the battery to developmental changes. In particular, we will examine the newly collected data from aging persons to determine whether modifications may be necessary, whether new tests may need to be developed, and whether it shows potential for detecting deterioration in cognition associated with aging or neurodegeneration, as in some participants with DS. As aging in DS is associated with high risk of early developing Alzheimer’s disease (AD), it is important to develop and validate cognitive tests that may be used to track the disease process and response to intervention. Cognition and neurodegeneration in older adults with FXS have been largely ignored, despite evidence of AD-related biomarker abnormalities and cognitive decline in some patients. The supplemental data collection from the FXS cohort will help to determine whether larger, more extensive longitudinal studies are justified to describe the natural history of this population and open the door for their participation in other research. The supplemental NIHTB-CB data collected from this aging group will provide critical preliminary information about its potential utility in future natural history or treatment studies.