Gazzina Stefano, Grassi Mario, Premi Enrico, Alberici Antonella, Benussi Alberto, Archetti Silvana, Gasparotti Roberto, Bocchetta Martina, Cash David M, Todd Emily G, Peakman Georgia, Convery Rhian S, van Swieten John C, Jiskoot Lize C, Seelaar Harro, Sanchez-Valle Raquel, Moreno Fermin, Laforce Robert, Graff Caroline, Synofzik Matthis, Galimberti Daniela, Rowe James B, Masellis Mario, Tartaglia Maria Carmela, Finger Elizabeth, Vandenberghe Rik, de Mendonça Alexandre, Tagliavini Fabrizio, Butler Chris R, Santana Isabel, Gerhard Alexander, Ber Isabelle Le, Pasquier Florence, Ducharme Simon, Levin Johannes, Danek Adrian, Sorbi Sandro, Otto Markus, Rohrer Jonathan D, Borroni Barbara
Neurophysiology Unit, ASST Spedali Civili Hospital, Brescia, Italy.
Department of Brain and Behavioral Science, Medical and Genomic Statistics Unit, University of Pavia, Pavia, Italy.
Neurobiol Aging. 2022 Jun;114:94-104. doi: 10.1016/j.neurobiolaging.2022.02.009. Epub 2022 Feb 26.
Frontotemporal dementia associated with granulin (GRN) mutations presents asymmetric brain atrophy. We applied a Minimum Spanning Tree plus an Efficiency Cost Optimization approach to cortical thickness data in order to test whether graph theory measures could identify global or local impairment of connectivity in the presymptomatic phase of pathology, where other techniques failed in demonstrating changes. We included 52 symptomatic GRN mutation carriers (SC), 161 presymptomatic GRN mutation carriers (PSC) and 341 non-carriers relatives from the Genetic Frontotemporal dementia research Initiative cohort. Group differences of global, nodal and edge connectivity in (Minimum Spanning Tree plus an Efficiency Cost Optimization) graph were tested via Structural Equation Models. Global graph perturbation was selectively impaired in SC compared to non-carriers, with no changes in PSC. At the local level, only SC exhibited perturbation of frontotemporal nodes, but edge connectivity revealed a characteristic pattern of interhemispheric disconnection, involving homologous parietal regions, in PSC. Our results suggest that GRN-related frontotemporal dementia resembles a disconnection syndrome, with interhemispheric disconnection between parietal regions in presymptomatic phases that progresses to frontotemporal areas as symptoms emerge.
与颗粒蛋白（GRN）突变相关的额颞叶痴呆表现为不对称性脑萎缩。我们将最小生成树加效率成本优化方法应用于皮质厚度数据，以测试图论测量是否能够识别病理症状前期连接性的整体或局部损害，而其他技术未能在此阶段显示出变化。我们纳入了来自遗传性额颞叶痴呆研究倡议队列的52名有症状的GRN突变携带者（SC）、161名症状前期GRN突变携带者（PSC）和341名非携带者亲属。通过结构方程模型测试了（最小生成树加效率成本优化）图中整体、节点和边连接性的组间差异。与非携带者相比，SC的整体图扰动有选择性受损，PSC则无变化。在局部水平，只有SC表现出额颞叶节点的扰动，但边连接性显示PSC存在涉及同源顶叶区域的半球间断开的特征模式。我们的结果表明，与GRN相关的额颞叶痴呆类似于一种断开综合征，在症状前期顶叶区域存在半球间断开，随着症状出现发展至额颞叶区域。
