Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia
Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia
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DOI：
10.1212/wnl.0000000000000583
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发表时间：
2014-07-08
期刊：
影响因子：
9.9
通讯作者：
van Swieten, John C.
中科院分区：
文献类型：
--
作者：
Dopper, Elise G. P.;Rombouts, Serge A. R. B.;van Swieten, John C.
目的：我们的目的是研究认知缺陷和结构和功能连接改变是否可以在症状发作前检测到MAPT（微管相关蛋白tau）或GRN（颗粒蛋白前）突变携带者。方法：在这项病例对照研究中，75名年龄在20-70岁、患额颞叶痴呆（FTD）风险为50%的健康个体接受了DNA筛查、神经心理学评估、结构MRI和功能磁共振成像。我们使用基于体素的形态测量和基于束的空间统计对灰质体积和扩散张量成像测量进行体素分析。通过静息状态fMRI扫描，我们评估了全脑与额岛皮质、前扣带中皮质和后扣带皮质的功能连接。结果：携带者（n = 39）和非携带者（n = 36）具有相似的神经心理表现，除了携带者的字母数字替换测试得分较低。在Stroop III、Rivermead行为记忆测试和快乐卡通测试中表现较差与携带者的年龄增加有关，但与对照组无关。与对照组相比，携带者右侧钩状肌束各向异性分数降低。与对照组相比，在携带者中发现了前扣带皮层与额岛和其他几个大脑区域之间的功能连接减少，并且与携带者的年龄增加相关，但与对照组无关。我们发现后扣带皮质连通性没有显著差异或年龄相关性。除了携带者的中央前回有一小簇较高的体积外，没有发现区域灰质体积的差异。结论：本研究表明，在FTD的最初症状出现之前，结构和功能连通性的改变就已经出现。这些发现表明，在未来的临床试验中，扩散张量成像和静息状态fMRI可能有潜力成为早期FTD的敏感生物标志物。
Objective: We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of MAPT (microtubule-associated protein tau) or GRN (progranulin) mutations.Methods: In this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk of frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, structural MRI, and fMRI. We used voxel-based morphometry and tract-based spatial statistics for voxel-wise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsular, anterior midcingulate, and posterior cingulate cortices.Results: Carriers (n = 39) and noncarriers (n = 36) had similar neuropsychological performance, except for lower Letter Digit Substitution Test scores in carriers. Worse performance on Stroop III, Rivermead Behavioral Memory Test, and Happ Cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy in the right uncinate fasciculus was found in carriers compared with controls. Reductions in functional connectivity between anterior midcingulate cortex and frontoinsula and several other brain regions were found in carriers compared with controls and correlated with higher age in carriers, but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found, except for a small cluster of higher volume in the precentral gyrus in carriers.Conclusions: This study demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.