Imaging endpoints for clinical trials in Alzheimer's disease.
Imaging endpoints for clinical trials in Alzheimer's disease.
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DOI：
10.1186/s13195-014-0087-9
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发表时间：
2014
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影响因子：
--
通讯作者：
Fox NC
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作者：
Cash DM;Rohrer JD;Ryan NS;Ourselin S;Fox NC
随着开发一种成功的阿尔茨海默病（AD）疾病修饰治疗的需求变得更加迫切，成像越来越多地用于治疗试验。我们提供了一个概述，不同的成像方式是如何使用在AD研究和目前的监管指南，其在临床试验中使用作为终点。我们回顾了目前文献中已发表的临床试验中有效性和安全性的成像终点结果。我们从轻度到中度AD的试验开始，其中成像（主要是磁共振成像（MRI））长期以来在纳入和排除标准中发挥作用;最近，MRI已被用于识别不良事件和测量脑萎缩率。使用正电子发射断层扫描的淀粉样蛋白成像的出现导致了将淀粉样蛋白测量作为终点的试验，并且偶然地认识到可能被招募到这些试验中的高比例的淀粉样蛋白阴性个体。正在进行的和计划中的试验现在通常包括多模态成像：淀粉样蛋白正电子发射断层扫描，MRI和其他模态。与此同时，最近在轻度至中度AD中进行的大规模试验的失败，以及认识到AD有很长的前驱期，推动了将研究转移到疾病的早期。成像与其他生物标志物一起在评估疗效方面具有特别重要的作用，因为常规临床结果在这些早期阶段检测治疗效果的能力可能有限。本文的在线版本（doi：10.1186/s13195-014-0087-9）包含补充材料，可供授权用户使用。
As the need to develop a successful disease-modifying treatment for Alzheimer’s disease (AD) becomes more urgent, imaging is increasingly used in therapeutic trials. We provide an overview of how the different imaging modalities are used in AD studies and the current regulatory guidelines for their use in clinical trials as endpoints. We review the current literature for results of imaging endpoints of efficacy and safety in published clinical trials. We start with trials in mild to moderate AD, where imaging (largely magnetic resonance imaging (MRI)) has long played a role in inclusion and exclusion criteria; more recently, MRI has been used to identify adverse events and to measure rates of brain atrophy. The advent of amyloid imaging using positron emission tomography has led to trials incorporating amyloid measurements as endpoints and incidentally to the recognition of the high proportion of amyloid-negative individuals that may be recruited into these trials. Ongoing and planned trials now commonly include multimodality imaging: amyloid positron emission tomography, MRI and other modalities. At the same time, the failure of recent large profile trials in mild to moderate AD together with the realisation that there is a long prodromal period to AD has driven a push to move studies to earlier in the disease. Imaging has particularly important roles, alongside other biomarkers, in assessing efficacy because conventional clinical outcomes may have limited ability to detect treatment effects in these early stages. The online version of this article (doi:10.1186/s13195-014-0087-9) contains supplementary material, which is available to authorized users.