Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.
Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.
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DOI：
10.1007/s00259-018-3933-3
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发表时间：
2018-06
影响因子：
9.1
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Pascoal TA;Mathotaarachchi S;Shin M;Park AY;Mohades S;Benedet AL;Kang MS;Massarweh G;Soucy JP;Gauthier S;Rosa-Neto P;Alzheimer’s Disease Neuroimaging Initiative
我们的目的是确定淀粉样蛋白（Aβ）和tau生物标志物水平与认知正常个体即将发生的阿尔茨海默病（AD）相关代谢下降相关。对120名认知正常的老年人进行阈值分析，通过模拟[18F]氟脱氧葡萄糖（[18F]FDG）作为[18F]florbetapir Aβ正电子发射断层扫描（PET）和脑脊液磷酸化tau生物标志物阈值的2年脑葡萄糖代谢下降。此外，使用一种新颖的体素分析框架，我们确定了所需的样本量，以测试估计25%的药物作用和80%的功率对2年内每个脑体素FDG摄取变化的影响。[18F]florbetapir标准化摄取值比和磷酸化tau水平比其各自的生物标志物异常阈值高出一个标准差以上的组合是临床前AD患者代谢下降的最佳预测指标。我们还发现，使用这些阈值的临床试验只需要100个人，就可以在2年内测试25%的药物对ad相关代谢下降的影响。这些结果强调了一个新的概念，即结合a β和tau阈值可以预测即将发生的神经退行性变，作为一种具有高统计能力的替代框架，用于测试疾病修饰疗法对临床前AD患者2年临床试验期间FDG摄取下降的影响[18F]。本文的在线版本（10.1007/s00259-018-3933-3）包含补充资料，仅供授权用户使用。
We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer’s disease (AD) - related metabolic decline in cognitively normal individuals. A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [18F]fluorodeoxyglucose ([18F]FDG) as a function of [18F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel. The combination of [18F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years. These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [18F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD. The online version of this article (10.1007/s00259-018-3933-3) contains supplementary material, which is available to authorized users.
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影响因子：
9.9
作者：
Lowe, Val J.;Weigand, Stephen D.;Petersen, Ronald C.
通讯作者：
Petersen, Ronald C.
影响因子：
11.2
作者：
Landau, Susan M.;Mintun, Mark A.;Joshi, Abhinay D.;Koeppe, Robert A.;Petersen, Ronald C.;Aisen, Paul S.;Weiner, Michael W.;Jagust, William J.
通讯作者：
Jagust, William J.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
16.2
作者：
Sperling, Reisa;Mormino, Elizabeth;Johnson, Keith
通讯作者：
Johnson, Keith
影响因子：
14
作者：
Gauthier, Serge;Albert, Marilyn;Middleton, Lefkos T.
通讯作者：
Middleton, Lefkos T.