家族性额颞叶痴呆前驱期的结构和功能脑连接。
Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia.
机构信息
From the Departments of Neurology (E.G.P.D., L.C.J., T.d.H., H.S., J.C.v.S.), Epidemiology (T.d.H.), and Neuropsychology (J.R.A.d.G., I.d.K.), Erasmus Medical Center, Rotterdam; Department of Radiology (E.G.P.D., S.A.R.B.R., I.M.V., M.A.v.B.), Leiden University Medical Center; Departments of Neurology (E.G.P.D.) and Clinical Genetics (A.R.H., P.R., J.C.v.S.), VU Medical Center, Amsterdam; Leiden Institute for Brain and Cognition (S.A.R.B.R., I.M.V., M.A.v.B.) and Institute of Psychology (S.A.R.B.R., I.M.V.), Leiden University; Department of Neurology (T.d.H.), Sint Franciscus Gasthuis, Rotterdam, the Netherlands; and Department of Neurology (W.W.S.) and Memory and Aging Center (W.W.S.), University of California, San Francisco.
出版信息
Neurology. 2014 Jul 8;83(2):e19-26. doi: 10.1212/WNL.0000000000000583.
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 Happé 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.
目的
我们旨在研究在 MAPT（微管相关蛋白 tau）或 GRN（颗粒蛋白前体）突变携带者的大队列中，是否可以在症状出现之前检测到认知缺陷以及结构和功能连接的变化。
方法
在这项病例对照研究中，75 名健康个体（年龄在 20-70 岁之间）具有 50%的额颞叶痴呆（FTD）风险，他们接受了 DNA 筛查、神经心理学评估、结构 MRI 和 fMRI。我们使用基于体素的形态计量学和基于束的空间统计学来进行灰质体积和扩散张量成像测量的体素分析。使用静息状态 fMRI 扫描，我们评估了额极、前扣带和后扣带皮质的全脑功能连接。
结果
携带者（n=39）和非携带者（n=36）的神经心理学表现相似，除了携带者的字母数字替换测试得分较低。携带者的 Stroop III、Rivermead 行为记忆测试和 Happé 卡通得分较差与年龄较大相关，但在对照组中则不然。与对照组相比，携带者的右侧钩束的各向异性分数降低。与对照组相比，携带者的前扣带皮层和额极之间以及其他几个脑区之间的功能连接减少，并且与携带者的年龄较大相关，但与对照组无关。我们在后扣带皮层连接中未发现显著差异或年龄相关性。除了携带者的中央前回体积稍高的小簇外，未发现区域性灰质体积的差异。
结论
本研究表明，结构和功能连接的改变在 FTD 首次出现症状之前就已经发生。这些发现表明，扩散张量成像和静息状态 fMRI 可能具有成为未来临床试验中早期 FTD 的敏感生物标志物的潜力。
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