Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Neurobiol Aging. 2019 May;77:169-177. doi: 10.1016/j.neurobiolaging.2018.12.009. Epub 2019 Jan 4.
The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.
神经退行性疾病的无症状前阶段的特征是存在结构脑变化，但没有明显的临床特征。我们着手研究功能网络弹性对无症状遗传额颞叶痴呆患者认知能力的影响。我们研究了来自携带 C9orf72、MAPT 或 PGRN 遗传异常家族的 172 人。从功能磁共振成像数据中提取网络，并使用图论分析进行评估。我们发现，尽管大脑体积和功能连接都丧失了，但在额颞叶痴呆症状发作的估计年龄之前的几年中，大脑功能网络的有效拓扑组织仍然得以维持。此后，功能网络效率显著下降。连通性的降低在高度连接的枢纽区域最为明显。大脑功能网络的拓扑效率和组织的度量预测了与有症状的额颞叶痴呆相关的认知功能障碍，并且连通性与额颞叶痴呆中的脑体积损失相关。我们提出，即使在萎缩和连接性在无症状前下降的情况下，维持大脑功能网络的有效组织也能支持认知健康。
