Disruption of functional connectivity in clinically normal older adults harboring amyloid burden.
Disruption of functional connectivity in clinically normal older adults harboring amyloid burden.
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DOI：
10.1523/jneurosci.3189-09.2009
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发表时间：
2009-10-07
期刊：
影响因子：
--
通讯作者：
Buckner RL
中科院分区：
文献类型：
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作者：
Hedden T;Van Dijk KR;Becker JA;Mehta A;Sperling RA;Johnson KA;Buckner RL
淀粉样蛋白沉积存在于20-50%的非痴呆老年人中，但其功能后果仍不清楚。目前的研究发现，淀粉样蛋白的积累与默认网络的功能破坏相关，如通过内在活性相关性测量的。使用[11 C]-匹兹堡化合物B（PiB）PET成像来评估纤维状淀粉样蛋白负荷，并分别进行功能性MRI（fMRI），对临床正常参与者（n=38，年龄60-88）进行表征。默认网络的完整性估计相关的静息状态功能磁共振成像时间过程中提取的先验区域，包括后扣带回，侧顶叶，内侧前额叶皮质。与淀粉样蛋白负荷低的参与者相比，淀粉样蛋白负荷高的临床正常参与者在默认网络中显示出显著降低的功能相关性。当淀粉样蛋白负荷作为一个连续的，而不是一个二分法，措施和控制年龄和结构性萎缩时，也观察到这些减少。通过接种后扣带皮层（阿尔茨海默病（AD）中淀粉样蛋白负荷高的区域）启动的全脑分析显示，默认网络中存在显著中断，包括海马结构的功能性断开。
Amyloid deposition is present in 20–50% of nondemented older adults yet the functional consequences remain unclear. The current study found that amyloid accumulation is correlated with functional disruption of the default network as measured by intrinsic activity correlations. Clinically normal participants (n=38, aged 60–88) were characterized using [11C]-Pittsburgh Compound B (PiB) PET imaging to estimate fibrillar amyloid burden and, separately, underwent functional MRI (fMRI). The integrity of the default network was estimated by correlating rest-state fMRI time courses extracted from a priori regions including the posterior cingulate, lateral parietal, and medial prefrontal cortices. Clinically normal participants with high amyloid burden displayed significantly reduced functional correlations within the default network relative to participants with low amyloid burden. These reductions were also observed when amyloid burden was treated as a continuous, rather than a dichotomous, measure and when controlling for age and structural atrophy. Whole-brain analyses initiated by seeding the posterior cingulate cortex, a region of high amyloid burden in Alzheimer1s disease (AD), revealed significant disruption in the default network including functional disconnection of the hippocampal formation.