Fujishima Motonobu, Kawaguchi Atsushi, Maikusa Norihide, Kuwano Ryozo, Iwatsubo Takeshi, Matsuda Hiroshi
Integrative Brain Imaging Center (IBIC), National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Department of Diagnostic Radiology, Kojinkai Josai Clinic, Maebashi, Gunma, Japan.
J Alzheimers Dis. 2017;56(1):75-88. doi: 10.3233/JAD-160621.
Little is known about the sample sizes required for clinical trials of Alzheimer's disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population.
The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker.
Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer's Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy.
The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures.
These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.
在日本人群中，关于使用系列脑磁共振成像（MRI）的萎缩测量指标进行阿尔茨海默病（AD）改善治疗的临床试验所需样本量，人们了解甚少。
本研究的主要目的是估计在日本，未来使用脑萎缩测量指标作为替代生物标志物进行AD改善治疗的临床试验需要多大的样本量。
利用537名日本阿尔茨海默病神经影像学计划（J-ADNI）参与者的数据，通过k均值归一化边界位移积分（KN-BSI）对全脑和海马体的变化率以及认知测量指标进行估计，并采用线性混合效应模型。我们还研究了将载脂蛋白E（ApoE）状态作为试验富集策略的潜在用途。
与AD和轻度认知障碍（MCI）的认知测量指标相比，海马体萎缩率所需的样本量更小。纳入ApoE状态可减少AD和MCI患者在萎缩测量指标方面的样本量。
这些结果表明，在针对日本人的AD改善治疗临床试验中，使用自动图像分析进行纵向海马体萎缩测量作为疾病进展生物标志物以及将ApoE状态作为试验富集策略具有潜在用途。
