阿尔茨海默病患者的内联网和外联网连通性及其与脑脊液生物标志物水平的关系。
Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.
机构信息
From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
出版信息
J Psychiatry Neurosci. 2017 Nov;42(6):366-377. doi: 10.1503/jpn.160190.
BACKGROUND
In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF).
METHODS
We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease.
RESULTS
Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas.
LIMITATIONS
The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used.
CONCLUSION
We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.
背景
在过去的十年中，许多研究报告称阿尔茨海默病患者的默认模式网络（DMN）内存在异常连接。然而，很少有研究调查其他网络及其与脑脊液（CSF）中获得的病理生理蛋白的关联。
方法
我们对轻度阿尔茨海默病患者、遗忘型轻度认知障碍（aMCI）患者和健康对照者进行了 3T 成像，并从 aMCI 和轻度阿尔茨海默病患者中收集了 CSF 样本。我们分析了 8 个网络中的 57 个区域。此外，我们还进行了相关测试，以研究 aMCI 和阿尔茨海默病患者的网络功能连接与 CSF 中蛋白质水平之间可能存在的关联。
结果
我们的样本包括 41 例阿尔茨海默病患者、35 例 aMCI 患者和 48 例对照者。我们发现，阿尔茨海默病患者的主要连接异常发生在 DMN 和任务正性网络之间：这些患者不仅表现出一些区域之间的相关性降低，而且还表现出相关性信号的反转（正相关而不是负相关）。aMCI 患者与阿尔茨海默病患者或对照者的连接无统计学差异。CSF 蛋白的异常水平与 aMCI 和轻度阿尔茨海默病组中几个区域之间的功能失连接有关，其范围远远超出 DMN 或颞区。
局限性
所呈现的数据本质上是横断面的，我们的发现取决于所使用的种子区域的选择。
结论
我们发现，DMN 和任务正性网络之间的主要功能连接异常，并且 CSF 生物标志物的病理水平与阿尔茨海默病患者的功能连接中断相关。
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