Chen Kewei, Roontiva Auttawut, Thiyyagura Pradeep, Lee Wendy, Liu Xiaofen, Ayutyanont Napatkamon, Protas Hillary, Luo Ji Luo, Bauer Robert, Reschke Cole, Bandy Daniel, Koeppe Robert A, Fleisher Adam S, Caselli Richard J, Landau Susan, Jagust William J, Weiner Michael W, Reiman Eric M
Banner Alzheimer's Institute, Phoenix, Arizona Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona Department of Neurology, College of Medicine, University of Arizona, Phoenix, Arizona Arizona Alzheimer's Consortium, Phoenix, Arizona
Banner Alzheimer's Institute, Phoenix, Arizona Arizona Alzheimer's Consortium, Phoenix, Arizona.
J Nucl Med. 2015 Apr;56(4):560-6. doi: 10.2967/jnumed.114.149732. Epub 2015 Mar 5.
In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments.
Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines.
As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines.
A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.
在本文中，我们描述了一种图像分析策略，该策略在追踪纵向淀粉样β（Aβ）正电子发射断层扫描（PET）变化以及评估Aβ修饰治疗方面具有更强的功效。
我们的目的是比较基于模板的小脑、脑桥和脑白质参考区域追踪24个月氟代贝他吡标准化摄取值（SUV）比率（SUVR）变化的功效；将这些变化与24个月的临床衰退相关联；并评估在可能患有阿尔茨海默病（pAD）的Aβ阳性（Aβ+）和Aβ阴性（Aβ-）患者、轻度认知障碍（MCI）患者、认知正常对照（NC）以及认知正常的载脂蛋白E4（APOE4）携带者和非携带者中Aβ修饰治疗的效果。我们使用了来自参与多中心阿尔茨海默病神经影像学倡议的332名Aβ+和Aβ-受试者的基线和随访（约24个月）氟代贝他吡PET扫描。每项拟议分析包括31名pAD患者、187名MCI患者和114名NC。脑白质与白质、小脑和脑桥的SUVR根据其纵向变异性、追踪Aβ+和Aβ-亚组以及认知正常的APOE4携带者和非携带者中纵向纤维状Aβ增加的能力、在随机临床试验中检测纤维状Aβ积累减弱或清除所需的样本量以及它们将24个月纤维状Aβ增加与临床衰退相关联的能力进行了表征。
正如预期的那样，脑白质与白质的SUVR变化显著较小，并且在检测Aβ+ pAD、MCI和NC受试者以及认知正常的APOE4携带者中24个月纤维状Aβ增加和评估Aβ修饰治疗效果方面具有显著更强的功效。它们还具有检测24个月Aβ增加与临床衰退之间显著关联的能力。
脑白质参考区域可能会提高追踪纵向纤维状Aβ增加、表征其与纵向临床衰退的关系以及在随机临床试验中评估Aβ修饰治疗的功效。
