The European Union AddNeuroMed program and the US-based Alzheimer Disease Neuroimaging Initiative (ADNI) are two large multi-center initiatives designed to collect and validate biomarker data for Alzheimer's disease (AD). Both initiatives use the same MRI data acquisition scheme. The current study aims to compare and combine magnetic resonance imaging (MRI) data from the two study cohorts using an automated image analysis pipeline and a multivariate data analysis approach. We hypothesized that the two cohorts would show similar patterns of atrophy, despite demographic differences and could therefore be combined. MRI scans were analyzed from a total of 1074 subjects (AD=295, MCI=444 and controls=335) using Freesurfer, an automated segmentation scheme which generates regional volume and regional cortical thickness measures which were subsequently used for multivariate analysis (orthogonal partial least squares to latent structures (OPLS)). OPLS models were created for the individual cohorts and for the combined cohort to discriminate between AD patients and controls. The ADNI cohort was used as a replication dataset to validate the model created for the AddNeuroMed cohort and vice versa. The combined cohort model was used to predict conversion to AD at baseline of MCI subjects at 1 year follow-up. The AddNeuroMed, the ADNI and the combined cohort showed similar patterns of atrophy and the predictive power was similar (between 80 and 90%). The combined model also showed potential in predicting conversion from MCI to AD, resulting in 71% of the MCI converters (MCI-c) from both cohorts classified as AD-like and 60% of the stable MCI subjects (MCI-s) classified as control-like. This demonstrates that the methods used are robust and that large data sets can be combined if MRI imaging protocols are carefully aligned.

译文

欧盟AddNeuroMed计划和美国的阿尔茨海默氏病神经成像计划 (ADNI) 是两个大型多中心计划,旨在收集和验证阿尔茨海默氏病 (AD) 的生物标志物数据。两种计划都使用相同的MRI数据采集方案。当前的研究旨在使用自动图像分析管道和多变量数据分析方法比较和组合来自两个研究队列的磁共振成像 (MRI) 数据。我们假设,尽管人口统计学存在差异,但这两个队列将显示相似的萎缩模式,因此可以合并。使用Freesurfer对总共1074名受试者 (AD = 295,MCI = 444和对照组 = 335) 的MRI扫描进行分析,Freesurfer是一种自动分割方案,其生成区域体积和区域皮质厚度测量,随后将其用于多变量分析 (正交偏最小二乘法到潜在结构 (OPLS))。为各个队列和组合队列创建了OPLS模型,以区分AD患者和对照组。ADNI队列用作复制数据集,以验证为AddNeuroMed队列创建的模型,反之亦然。联合队列模型用于预测MCI受试者在1年随访时的基线转换为AD。Adneuromed,ADNI和联合队列显示出相似的萎缩模式,并且预测能力相似 (介于80和90% 之间)。组合模型还显示出预测从MCI到AD的转化的潜力,导致来自被分类为AD-like的两个队列的MCI转换器 (MCI-c) 的71% 和被分类为对照-like的稳定MCI受试者 (MCI-s) 的60%。这表明所使用的方法是可靠的,并且如果仔细对齐MRI成像协议,则可以组合大数据集。

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