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

阿尔茨海默病预防试验的新认知和功能测量

• 批准号: 10179171
• 负责人: Terry Goldberg
• 金额: $ 40.02万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10179171
• 关键词: Administrative Supplement; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Attenuated; Back; Biological Markers; Cellular Phone; Clinical Trials; Cognitive; Competence; Data; Digit structure; Episodic memory; Family history of; Goals; Letters; Measures; Paper; Participant; Performance; Population; Prevention trial; Randomized; Structure; Telephone; Testing; Thinness; apolipoprotein E-4; base; carrier status; computerized; design; executive function; hippocampal atrophy; innovation; instrument; memory recognition; novel; pre-clinical; processing speed

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.

项目概要 人们越来越认识到实践效应和上限效应可能导致类型 1 或 鉴于连续评估的必要性，涉及早期 AD 人群的临床试验中存在 2 类错误。 该提案的总体目标是验证新颖的认知和日常功能测量， 临床前阿尔茨海默病的实践效果急剧减弱，并且不易出现天花板效应 疾病（AD）试验，其中参与者的认知能力处于正常范围内。为了实现这一目标，我们将进行 一项创新的平行小组研究，其中 320 名健康、无认知障碍的老年受试者 根据评估类型​​（新仪器与现有仪器）随机分配到两组中的一组并接受 一年内进行三次连续评估。我们将采用这种并行组设计来维持 临床试验的结构，同时强调新颖和既定措施之间的对比 并且完全避免了它们之间的任何干扰作用。我们新颖的认知测量包括测试 执行功能、情景记忆和处理速度结合成一个复合体。我们的功能性 措施涉及基于计算机化性能的、与生态相关的工具活动。我们将 比较我们新颖的无练习效果 (NPE) 认知电池和迈阿密计算机化功能 根据 PACC、ADAS-Cog 和 FAQ 等既定措施进行评估量表 (CFAS)。在 初步数据表明，我们的新措施削弱了实践效果，重测可靠性高， 等效的替代形式，并且缺乏天花板效应。此外，我们还将检查一些生物标志物 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 稀疏特征、AD 家族史），以评估这些已知措施的敏感性 生物标志物等为认知和功能测试的有效性提供了支持或反对的证据。