Commentary on Composite cognitive and functional measures for early stage Alzheimer's disease trials.
Commentary on Composite cognitive and functional measures for early stage Alzheimer's disease trials.
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DOI：
10.1002/dad2.12012
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Papp KV
中科院分区：
文献类型：
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作者：
Rentz DM;Papp KV
证明疾病缓解治疗在阿尔茨海默病 (AD) 连续体中是有效且具有临床意义的，导致了心理测量复合材料的发展，试图捕获 AD 轨迹的广泛认知和功能变化特征。正如 Schneider 和 Goldberg（2019）指出的那样，复合量表对于临床试验领域来说并不新鲜，但随着治疗进入 AD 的早期临床前阶段，它们变得越来越有吸引力。在此，作者对 12 种此类复合材料进行了严格审查，这些复合材料被开发为 AD 临床试验的主要结果指标。然而，他们认为，这些量表的开发是在没有关注基本心理测量原理、缺乏替代形式以及临床试验之外的验证的情况下实施的（Schneider & Goldberg，2019）。他们进一步认为，这些综合措施可能不符合 AD 临床表型或神经生物学的现实。在这篇评论中，我们从派生 AD 二级预防试验复合材料（特别是临床前阿尔茨海默病认知复合材料 [PACC]）的角度解决了对作者的一些批评。我们将讨论 (1) 认知综合的价值有利于单一认知测试或领域评分；(2) 在临床试验中使用这些综合的心理测量验证，以及 (3) 在 AD 的临床表型和神经生物学背景下选择 PACC 测量的考虑因素。大多数 AD 临床试验都是在疾病症状阶段完成的。我们的领域最近向二级预防的转变需要认知结果的相应演变，以便能够在 AD 临床前阶段捕获更微妙的认知变化。这种需求，再加上来自老年人观察研究的可用纵向和生物标志物数据，重新激发了神经心理学家和统计学家使用数据驱动和理论驱动的方法来开发和迭代
Demonstrating that disease-modifying treatments are effective and clinically meaningful across the Alzheimer disease (AD) continuum has led to the development of psychometric composites that attempt to capture a broad range of cognitive and functional changes characteristic of the AD trajectory. As Schneider and Goldberg (2019) point out, composite scales are not new to the clinical trial arena, but they are increasingly more attractive as treatment has moved into earlier preclinical stages of AD. Herein the authors provide a critical review of 12 such composites that were developed as primary outcome measures for AD clinical trials. They argue, however, that the development of these scales has been implemented without attention to basic psychometric principals, absence of alternate forms, and validation outside its use in the clinical trial (Schneider & Goldberg, 2019). They further argue that these composite measures may not fit the realities of the clinical phenotypes or neurobiology of AD. In this commentary, we address several criticisms of the authors from our perspective of deriving composites for secondary AD prevention trials (specifically, the Preclinical Alzheimer’s Cognitive Composite [PACC]). We will speak to (1) the value of cognitive composites in favor of a single cognitive test or domain score;(2) the psychometric validation of these composites prior to use in a clinical trial, and (3) considerations made in selecting PACC measures in the context of the clinical phenotype and neurobiology of AD. Most clinical trials for AD have been completed at symptomatic stages of disease. Our field’s recent shift toward secondary prevention has necessitated a corresponding evolution in cognitive outcomes that are able to capture more subtle cognitive change at the preclinical stage of AD. This need, combined with the available longitudinal and biomarker data from observational studies in older adults, has reenergized both neuropsychologists and statisticians to use both datadriven and theoretically driven approaches to develop and iterate on