Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Neurobiol Aging. 2018 Apr;64:15-24. doi: 10.1016/j.neurobiolaging.2017.11.014. Epub 2017 Dec 7.
Recent findings show that structural network topology is disrupted in Alzheimer's disease (AD), with changes occurring already at the prodromal disease stages. Amyloid accumulation, a hallmark of AD, begins several decades before symptom onset, and its effects on brain connectivity at the earliest disease stages are not fully known. We studied global and local network changes in a large cohort of cognitively healthy individuals (N = 299, Swedish BioFINDER study) with and without amyloid-β (Aβ) pathology (based on cerebrospinal fluid Aβ42/Aβ40 levels). Structural correlation matrices were constructed based on magnetic resonance imaging cortical thickness data. Despite the fact that no significant regional cortical atrophy was found in the Aβ-positive group, this group exhibited an altered global network organization, including decreased global efficiency and modularity. At the local level, Aβ-positive individuals displayed fewer and more disorganized modules as well as a loss of hubs. Our findings suggest that changes in network topology occur already at the presymptomatic (preclinical) stage of AD and may precede detectable cortical thinning.
最近的研究结果表明，阿尔茨海默病（AD）患者的结构网络拓扑结构被打乱，并且这种变化已经发生在疾病的前驱期。淀粉样蛋白的积累是 AD 的一个标志，它在症状出现前几十年就开始了，但其对疾病早期阶段大脑连接的影响尚不完全清楚。我们在一个认知健康个体的大型队列中（N=299，瑞典生物发现者研究）研究了全球和局部网络的变化，这些个体中有（基于脑脊液 Aβ42/Aβ40 水平）和没有淀粉样蛋白-β（Aβ）病理学。基于磁共振成像皮质厚度数据构建了结构相关矩阵。尽管在 Aβ阳性组中没有发现明显的区域性皮质萎缩，但该组表现出全局网络组织的改变，包括全局效率和模块性降低。在局部水平上，Aβ阳性个体的模块数量更少且更无序，并且枢纽丧失。我们的研究结果表明，网络拓扑结构的变化已经发生在 AD 的无症状（临床前）阶段，并且可能早于可检测到的皮质变薄。
