Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Psychology, Leiden University, Leiden, the Netherlands.
Neurobiol Aging. 2019 Apr;76:115-124. doi: 10.1016/j.neurobiolaging.2018.12.017. Epub 2019 Jan 7.
In genetic frontotemporal dementia, cross-sectional studies have identified profiles of presymptomatic neuroanatomical loss for C9orf72 repeat expansion, MAPT, and GRN mutations. In this study, we characterize longitudinal gray matter (GM) and white matter (WM) brain changes in presymptomatic frontotemporal dementia. We included healthy carriers of C9orf72 repeat expansion (n = 12), MAPT (n = 15), GRN (n = 33) mutations, and related noncarriers (n = 53), that underwent magnetic resonance imaging at baseline and 2-year follow-up. We analyzed cross-sectional baseline, follow-up, and longitudinal GM and WM changes using voxel-based morphometry and cortical thickness analysis in SPM and tract-based spatial statistics in FSL. Compared with noncarriers, C9orf72 repeat expansion carriers showed lower GM volume in the cerebellum and insula, and WM differences in the anterior thalamic radiation, at baseline and follow-up. MAPT mutation carriers showed emerging GM temporal lobe changes and longitudinal WM degeneration of the uncinate fasciculus. GRN mutation carriers did not show presymptomatic neurodegeneration. This study shows distinct presymptomatic cross-sectional and longitudinal patterns of GM and WM changes across C9orf72 repeat expansion, MAPT, and GRN mutation carriers compared with noncarriers.
在遗传性额颞叶痴呆中，横断面研究已经确定了 C9orf72 重复扩展、MAPT 和 GRN 突变的无症状神经解剖学丧失的特征。在这项研究中，我们描述了无症状额颞叶痴呆的纵向灰质 (GM) 和白质 (WM) 脑变化。我们纳入了健康的 C9orf72 重复扩展 (n = 12)、MAPT (n = 15)、GRN (n = 33) 突变携带者和相关非携带者 (n = 53)，他们在基线和 2 年随访时接受了磁共振成像。我们使用 SPM 中的基于体素的形态计量学和皮质厚度分析以及 FSL 中的基于束的空间统计学分析，分析了横断面基线、随访和纵向 GM 和 WM 的变化。与非携带者相比，C9orf72 重复扩展携带者在基线和随访时小脑和脑岛的 GM 体积较低，前丘脑辐射的 WM 差异较大。MAPT 突变携带者出现了颞叶 GM 变化和钩束的纵向 WM 退化。GRN 突变携带者没有表现出无症状的神经退行性变。这项研究表明，与非携带者相比，C9orf72 重复扩展、MAPT 和 GRN 突变携带者存在明显的无症状横断面和纵向 GM 和 WM 变化模式。
