阿尔茨海默病(AD)是一种与衰老密切相关的慢性进行性神经退行性疾病。AD是否通过靶向局部大脑区域而起源,并在疾病严重程度进展中传播到大脑的其余部分,这是一个未知答案的问题。这里,我们的目标是通过观察扩散张量脑网络的差异,在群体层面提供这个问题的答案。特别是,利用阿尔茨海默病神经影像学倡议(ADNI)的数据,定义了四个不同的组(所有组都按年龄匹配,性别和教育水平):G1(N1=36,健康对照受试者,Control),G2(N2=36,早期轻度认知障碍,EMCI),G3(N3=36,晚期轻度认知障碍,LMCI)和G4(N4=36,AD)。在三个疾病阶段比较了扩散张量脑网络:I期(对照与EMCI),第二阶段(控制与LMCI)和第三阶段(对照与AD).分组比较采用多变量距离矩阵回归分析,一种在基因组学中诞生的技术,最近被提出来处理大脑功能网络,但这里适用于扩散张量数据。结果有三个方面:第一,在I阶段没有发现显著差异。在与记忆功能密切相关的子网络的连接模式的II期发现了显着差异(包括海马的一部分,杏仁核,内嗅皮层,梭状回,下颞中回,海马旁回和颞极)。第三,在第三阶段发现了整个AD大脑的广泛断开,对第二阶段出现的相同记忆子网络的影响更大,加上其他新的子网,包括默认模式网络,媒体视觉网络,额顶叶区和纹状体。我们的结果与随着疾病严重程度的增加而出现连接性进行性改变的情况一致,并提供可能参与这种退行性过程的大脑区域。需要对纵向数据应用相同策略的进一步研究才能充分证实这种情况。
Alzheimer\'s disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer\'s Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD). Diffusion-tensor brain networks were compared across three disease stages: stage I (Control vs. EMCI), stage II (Control vs. LMCI) and stage III (Control vs. AD). The group comparison was performed using the multivariate distance matrix regression analysis, a technique that was born in genomics and was recently proposed to handle brain functional networks, but here applied to diffusion-tensor data. The results were threefold: First, no significant differences were found in stage I. Second, significant differences were found in stage II in the connectivity pattern of a subnetwork strongly associated to memory function (including part of the hippocampus, amygdala, entorhinal cortex, fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and temporal pole). Third, a widespread disconnection across the entire AD brain was found in stage III, affecting more strongly the same memory subnetwork appearing in stage II, plus the other new subnetworks, including the default mode network, medial visual network, frontoparietal regions and striatum. Our results are consistent with a scenario where progressive alterations of connectivity arise as the disease severity increases and provide the brain areas possibly involved in such a degenerative process. Further studies applying the same strategy to longitudinal data are needed to fully confirm this scenario.