Department of Geriatric Psychiatry, New York State Psychiatric Institute.
Department of Psychiatry.
Curr Opin Neurol. 2022 Apr 1;35(2):240-248. doi: 10.1097/WCO.0000000000001041.
We comprehensively examined recent advancements in developing novel cognitive measures that could significantly enhance detection of outcome changes in Alzheimer's disease clinical trials. Previously established measures were largely limited in their ability to detect subtle cognitive declines in preclinical stages of Alzheimer's disease, particularly due to weak psychometric properties (including practice effects and ceiling effects) and requirement of in-person visits that impacted ascertainment.
We present novel cognitive measures that were designed to exhibit reduced practice effects and stronger correlations with Alzheimer's disease biomarkers. In addition, we summarized some recent efforts in developing remote testing measures protocols that are aimed to overcome the limitations and inconvenience of in-person testing, and digital phenotyping, which analyses subtle forms of digital behaviour indicative of cognitive phenotypes. We discuss each measure's prognostic accuracy and potential utility in Alzheimer's disease research while also commenting on their limitations. We also describe our study, the Development of Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD), that employed a parallel group design in which novel measures and established measures are compared in a clinical trials armature.
Overall, we believe that these recent developments offer promising improvements in accurately detecting clinical and preclinical cognitive changes in the Alzheimer's disease spectrum; however, further validation of their psychometric properties and diagnostic accuracies is warranted before reliably implementing these novel measures in Alzheimer's disease clinical trials.
我们全面考察了开发新型认知测量方法的最新进展，这些方法可显著提高阿尔茨海默病临床试验中对结果变化的检测能力。先前建立的方法在检测阿尔茨海默病临床前阶段的细微认知下降方面能力有限，主要是因为它们的心理测量特性（包括练习效应和天花板效应）较弱，并且需要亲自就诊，这影响了检测的确定。
我们提出了一些新的认知测量方法，这些方法旨在减少练习效应，并与阿尔茨海默病生物标志物具有更强的相关性。此外，我们总结了一些最近在开发远程测试测量方案方面的努力，这些方案旨在克服亲自测试的限制和不便，以及数字表型分析，这是对认知表型的细微数字行为进行分析。我们讨论了每种测量方法在阿尔茨海默病研究中的预后准确性和潜在用途，同时也对其局限性进行了评论。我们还描述了我们的研究，即预防阿尔茨海默病试验的新型措施开发（NoMAD），该研究采用平行组设计，在临床试验中比较新型措施和已建立的措施。
总之，我们相信这些最新进展为准确检测阿尔茨海默病谱中的临床和临床前认知变化提供了有希望的改进；然而，在可靠地将这些新型措施应用于阿尔茨海默病临床试验之前，还需要进一步验证其心理测量特性和诊断准确性。
