AstraZeneca R&D, Södertälje, Sweden.
Acta Neurol Scand. 2014 Feb;129(2):114-22. doi: 10.1111/ane.12153. Epub 2013 Jun 13.
To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials.
Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure.
The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed.
Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items.
Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population.
This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.
进行心理计量分析，以确定用于阿尔茨海默病试验的认知测量工具的充分性。
阿尔茨海默病评估量表-认知（ADAS-Cog）和神经心理测试电池（NTB）均为阿尔茨海默病临床试验的经过验证的结局测量指标，也被批准用于监管目的。然而，它们在测量认知功能方面的可比性尚不清楚。事实上，许多最近的阿尔茨海默病患者试验都失败了，有人质疑 ADAS-Cog 是否仍然是一种敏感的测量方法。
本文根据 AstraZeneca 进行的一项临床试验（NCT01024660）的数据进行了事后分析，检查了 ADAS-Cog 和 NTB 的心理计量学特性，该试验纳入了轻度至中度阿尔茨海默病（AD）患者，其简易精神状态检查（MMSE）总分为 16-24。采用相关统计方法评估了可接受性、可靠性、不同类型的有效性和检测变化的能力。分析了两项测试的总分数以及两项测试的单独领域，包括韦氏记忆量表（WMS）、雷氏听觉言语学习测验（RAVLT）和德利斯科尔-卡普兰执行功能系统（D-KEFS）言语流畅性条件。
总体而言，NTB 表现良好，具有可接受的可靠性和检测变化的能力，而 ADAS-Cog 的心理计量学特性不足，包括在轻度 AD 患者中 11 个 ADAS-Cog 项目中的 8 个项目存在天花板效应，以及一些项目的测试-重测信度低。
基于对同一患者样本的直接比较，我们看到 NTB 在评估轻度至中度 AD 患者人群的认知功能方面优于 ADAS-Cog。结果表明，并非所有 ADAS-Cog 项目都与轻度和中度 AD 人群相关。
这项验证性研究表明，NTB 具有令人满意的心理计量学特性，而 ADAS-Cog 则存在心理计量学上的不足。
