Koch Kathrin, Myers Nicholas E, Göttler Jens, Pasquini Lorenzo, Grimmer Timo, Förster Stefan, Manoliu Andrei, Neitzel Julia, Kurz Alexander, Förstl Hans, Riedl Valentin, Wohlschläger Afra M, Drzezga Alexander, Sorg Christian
Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany.
Department of Neuroradiology TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München (TUM), 81675 Munich, Germany Department of Experimental Psychology, Oxford University, Oxford OX1 3UD, UK.
Cereb Cortex. 2015 Dec;25(12):4678-88. doi: 10.1093/cercor/bhu151. Epub 2014 Jul 4.
Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-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 Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-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 Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.
淀粉样蛋白β病理（Aβ）和认知障碍是阿尔茨海默病（AD）的特征；然而，将Aβ病理与认知障碍联系起来的神经机制尚未完全明确。大规模内在连接网络（ICN）可能是这种联系的潜在候选者：Aβ病理在AD早期会影响特定网络，这些网络显示出连接中断，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，ICN的区域变化在静息和认知任务状态下持续存在，可能通过内在连接受损将Aβ病理与认知障碍联系起来。在前驱AD患者和健康对照中使用了反映体内Aβ病理的匹兹堡化合物B（PiB）正电子发射断层扫描、静息态功能磁共振成像、任务功能磁共振成像和认知测试。在患者中，相对于健康对照，静息时默认模式网络（DMN）在内侧顶叶皮质的功能连接（FC）降低，在需要注意力的任务期间同一区域相对增加，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也发现了相应的结果。最后，结构方程模型证实了DMN静息态FC对Aβ病理与认知障碍之间关联的直接影响。数据提供了证据，表明内在网络连接中断将Aβ病理与早期AD中的认知障碍联系起来。
