Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease
Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease
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DOI：
10.1093/cercor/bhu151
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发表时间：
2015-12-01
期刊：
影响因子：
3.7
通讯作者：
Sorg, Christian
中科院分区：
文献类型：
--
作者：
Koch, Kathrin;Myers, Nicholas E.;Sorg, Christian
淀粉样β病理学（A β）和认知受损是阿尔茨海默病（AD）的特征;然而，将A β病理学与认知受损联系起来的神经机制尚未完全了解。大规模内在连接网络（ICN）是这种联系的潜在候选者：β病理学影响早期AD中的特定网络，这些网络显示出中断的连接，并且它们处理AD中受损的特定认知功能，如记忆或注意力。我们假设，在AD中，持续存在于休息和认知任务状态的ICN的区域变化可能通过受损的内在连接将A β病理与认知受损联系起来。匹兹堡化合物B（Pi B）-正电子发射断层扫描反映体内A β-病理，静息状态功能磁共振成像，任务功能磁共振成像，认知测试被用于前驱AD患者和健康对照。在患者中，默认模式网络（DMN）功能连接（FC）在休息期间相对于健康对照组在内侧顶叶皮层中减少，在需要注意力的任务期间在同一区域中相对增加，并且与患者的认知障碍相关。局部PiB摄取与DMN连接呈负相关。重要的是，在注意力网络的右侧顶叶区域发现了相应的结果。最后，结构方程模型证实了DMN静息态FC对A β病理学和认知障碍之间的关联的直接影响。数据提供的证据表明，破坏内在的网络连接链接A β病理与早期AD的认知障碍。
Amyloid-beta pathology (A beta) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link A beta-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: A beta-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link A beta-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo A beta-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between A beta-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links A beta-pathology with cognitive impairment in early AD.