Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Mol Psychiatry. 2020 Jan;25(1):230-239. doi: 10.1038/s41380-018-0067-8. Epub 2018 May 9.
The aim of this study was two-fold: (i) to investigate structural and functional brain network architecture in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), stratified in converters (c-aMCI) and non-converters (nc-aMCI) to AD; and to assess the relationship between healthy brain network functional connectivity and the topography of brain atrophy in patients along the AD continuum. Ninety-four AD patients, 47 aMCI patients (25 c-aMCI within 36 months) and 53 age- and sex-matched healthy controls were studied. Graph analysis and connectomics assessed global and local, structural and functional topological network properties and regional connectivity. Healthy topological features of brain regions were assessed based on their connectivity with the point of maximal atrophy (epicenter) in AD and aMCI patients. Brain network graph analysis properties were severely altered in AD patients. Structural brain network was already altered in c-aMCI patients relative to healthy controls in particular in the temporal and parietal brain regions, while functional connectivity did not change. Structural connectivity alterations distinguished c-aMCI from nc-aMCI cases. In both AD and c-aMCI, the point of maximal atrophy was located in left hippocampus (disease-epicenter). Brain regions most strongly connected with the disease-epicenter in the healthy functional connectome were also the most atrophic in both AD and c-aMCI patients. Progressive degeneration in the AD continuum is associated with an early breakdown of anatomical brain connections and follows the strongest connections with the disease-epicenter. These findings support the hypothesis that the topography of brain connectional architecture can modulate the spread of AD through the brain.
本研究旨在探索阿尔茨海默病（AD）和遗忘型轻度认知障碍（aMCI）患者的脑结构和功能网络拓扑结构，其中 aMCI 患者分为转化者（c-aMCI）和非转化者（nc-aMCI）；评估 AD 连续体患者健康脑网络功能连接与脑萎缩拓扑之间的关系。研究共纳入 94 例 AD 患者、47 例 aMCI 患者（其中 25 例在 36 个月内转化为 AD）和 53 名年龄和性别匹配的健康对照者。通过图分析和连接组学评估了全局和局部、结构和功能拓扑网络特性以及区域连接。根据 AD 和 aMCI 患者的最大萎缩点（中心点）评估健康脑区的拓扑特征。AD 患者的脑网络图分析特性发生了严重改变。与健康对照组相比，c-aMCI 患者的结构性脑网络已经发生改变，特别是在颞叶和顶叶脑区，而功能连接没有改变。结构性连接改变可区分 c-aMCI 与 nc-aMCI 病例。在 AD 和 c-aMCI 中，最大萎缩点位于左侧海马体（疾病中心点）。在健康功能连接体中与疾病中心点连接最强的脑区在 AD 和 c-aMCI 患者中也最萎缩。AD 连续体中的进行性退化与解剖学脑连接的早期破坏有关，并遵循与疾病中心点的最强连接。这些发现支持这样一种假设，即脑连接拓扑结构的拓扑结构可以通过大脑调节 AD 的传播。
