Metis Cognition Ltd., Kilmington Common, Wiltshire, BA12 6QY, UK.
Alzheimer Center, Amsterdam, The Netherlands.
Alzheimers Res Ther. 2018 Jun 29;10(1):61. doi: 10.1186/s13195-018-0386-7.
The FDA have recently published draft guidance for the development of treatments for early Alzheimer's disease. Key features of this guidance are the advocacy of sensitive cognitive measures and a taxonomy of disease severity. Whilst desirable patterns of cognitive-functional improvement are included, specific measures, and the magnitude of required effects, are not described.
We describe key elements of the guidance content, especially with regard targeting key cognitive domains and the means by which they might be efficiently indexed in the disease stages included in the guidance. We discuss also the opportunities to assess cognitive performance in 'Stage 2' and 'Stage 3' patients, as well as the possibilities for effectively assessing function in the latter category. In this section we review candidate cognitive assessments that we judge are capable of delivering on the guidance specification for sensitive neuropsychological measures. This includes detailed consideration of the ADCS-PACC and Catch-Cog initiatives. With respect to the magnitude of effects, we propose that standardised effect sizes of 0.3 represent a reasonable level of efficacy based on the observation that already marketed drugs on average deliver this level of improvement.
We propose the use of cognitive measures in stage 2 patients to index the cognitive skills known to be compromised early in the Alzheimer's disease process. We recommend extending the traditional interest in episodic memory to include sensitive, reliable and valid measures of attention, working memory and aspects of executive function. We propose a focus on these additional cognitive abilities based on evidence that performance on tests of these domains is moderately well related to functional skills.
美国食品和药物管理局（FDA）最近发布了针对早期阿尔茨海默病治疗方法开发的指导草案。该指南的主要特点是倡导使用敏感的认知测量方法和疾病严重程度分类法。虽然包括了理想的认知-功能改善模式，但没有描述具体的测量方法和所需效果的幅度。
我们描述了指南内容的关键要素，特别是针对关键认知领域的目标以及在指南中包含的疾病阶段中有效地对其进行索引的方法。我们还讨论了评估“第 2 阶段”和“第 3 阶段”患者认知表现的机会，以及在后一类患者中有效评估功能的可能性。在本节中，我们回顾了我们认为有能力满足指导中关于敏感神经心理学测量标准的候选认知评估。这包括对 ADCS-PACC 和 Catch-Cog 计划的详细考虑。关于效果幅度，我们提出，基于已经上市的药物平均可实现这一水平的改善这一观察，标准效应大小为 0.3 代表了合理的疗效水平。
我们建议在第 2 阶段患者中使用认知测量来对在阿尔茨海默病过程早期受损的认知技能进行索引。我们建议将对情景记忆的传统兴趣扩展到包括敏感、可靠和有效的注意力、工作记忆和执行功能方面的测量。我们基于这些领域的测试表现与功能技能有中度相关性的证据，建议关注这些额外的认知能力。
