Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.
Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.
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DOI：
10.3389/fnagi.2016.00015
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发表时间：
2016
影响因子：
4.8
通讯作者：
Ding M
中科院分区：
文献类型：
--
作者：
Jiang Y;Huang H;Abner E;Broster LS;Jicha GA;Schmitt FA;Kryscio R;Andersen A;Powell D;Van Eldik L;Gold BT;Nelson PT;Smith C;Ding M
β-淀粉样蛋白（Aβ）斑块和tau相关神经变性是阿尔茨海默病（AD）的病理标志。阿尔茨海默病生物标志物，包括脑脊液（CSF）中测量的生物标志物，在预测未来阿尔茨海默病风险和认知能力下降方面的应用仍在完善中。在这里，我们探索了默认模式网络（DMN）中功能连接（FC）模式、年龄、脑脊液生物标志物（Aβ42和pTau181）和老年人认知状态之间的潜在关系。研究人员探索了FC的多种测量方法，包括一种新的基于时间序列的测量方法[总相互依赖性（TI）]。在我们的27名认知正常的老年人样本中，没有发现Aβ42或pTau181水平与认知评分或区域脑容量之间的显著关联。然而，我们在静息状态和短期记忆任务中观察到这些生物标志物与DMN中FC测量之间的一些新的关系。首先，在休息和任务期间，双侧前部中颞回之间的连接增加与脑脊液Aβ42和Aβ42/pTau181比值（反映较低的AD风险）升高有关。其次，在短期记忆任务期间，双侧顶叶连通性增加与CSF pTau181水平升高（反映更高的AD风险）相关，而在休息期间则没有。第三，在活动任务期间，左中颞叶和左顶叶皮层之间的连通性增加与整体认知状态下降有关，但与脑脊液生物标志物无关。最后，我们发现我们的新TI方法对脑脊液a β42连接关系更敏感，而传统的互相关方法对脑脊液pTau181水平和认知状态更敏感。随着进一步完善，静息状态连接和任务驱动连接测量有望作为认知正常老年人Aβ和pTau负担的非侵入性神经影像学标志物。
β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults.