Novel Cognitive and Functional Measure for Alzheimer's Disease Prevention Trials

项目总结 人们越来越认识到，练习效应和天花板效应可能导致类型1或 考虑到系列评估的必要性，涉及早期AD人群的临床试验中的2型错误。 这项建议的首要目标是验证新的认知和日常功能衡量标准 大大减弱了练习效果，不容易出现天花板效应，用于临床前阿尔茨海默氏症 疾病(AD)试验，参与者在认知上处于正常范围内。为了实现这一点，我们将进行 一项创新的平行小组研究，其中320名健康的、无认知障碍的老年受试者 根据评估类型(新工具与已建立的工具)和接收情况随机分为两组之一 在一年内进行了三次系列评估。我们将采用这种平行分组设计，以保持 临床试验的结构，虽然相似，但突出了新措施和现有措施之间的差异 并且完全避免了它们之间的任何干扰效应。我们的新认知测量包括测试 执行功能、情景记忆和处理速度结合在一起成为一个单一的复合体。我们的职能部门 措施涉及计算机化的、基于绩效的、与生态相关的工具活动。我们会 比较我们的新型无练习效应(NPE)认知电池和迈阿密计算机化功能 对照包括PACC、ADAS-Cog和FAQ在内的既定措施的评估表(CFAS)。在……里面 初步数据显示，我们的新措施减弱了实践效果，重测可靠性高， 等同的替代形式，没有天花板效应。此外，我们还将检测几个生物标志物和 可能增加AD风险的标志物(例如，APOE e4携带者状态、海马萎缩和AD皮质 细化签名、阿尔茨海默病家族史)，以评估这些措施对这些已知因素的敏感性 生物标记物等提供了支持或反对认知和功能测试有效性的证据。

PROJECT SUMMARY It has become increasingly appreciated that practice effects and ceiling effects could result in type 1 or type 2 errors in clinical trials involving early stage AD populations, given the necessity of serial assessments. This proposal has the overarching goal of validating novel cognitive and everyday functional measures that have sharply attenuated practice effects and are not prone to ceiling effects for use in preclinical Alzheimer's disease (AD) trials in which participants are cognitively within normal limits. To implement this, we will conduct an innovative parallel group study in which 320 healthy, non-cognitively impaired older subjects are randomized to one of two groups based on assessment type (novel instruments vs. established) and receive three serial assessments over a one year period. We will employ this parallel group design in order to maintain the structure of a clinical trial, while pari passu, highlighting contrasts between novel and established measures and completely avoiding any interference effects between them. Our novel cognitive measures include tests of executive function, episodic memory, and processing speed combined into a single composite. Our functional measures involve computerized performance based, ecologically relevant instrumental activities. We will compare our novel No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS) against established measures that include the PACC, ADAS-Cog, and FAQ. In preliminary data our novel measures demonstrated attenuated practice effects, high test-retest reliabilities, equivalent alternate forms, and lack of ceiling effects. Moreover, we will also examine several biomarkers and markers that may increase risk for AD (e.g., APOE e4 carrier status, hippocampal atrophy and AD cortical thinning signature, family history of AD) in order to assess the sensitivity of the measures to these known biomarkers and so provide evidence for or against the validity of the cognitive and functional tests.