Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
MRI Research Center, University of Campania "Luigi Vanvitelli", Naples, Italy.
Mov Disord. 2021 Jul;36(7):1603-1616. doi: 10.1002/mds.28541. Epub 2021 Feb 27.
Functional brain connectivity alterations may be detectable even before the occurrence of brain atrophy, indicating their potential as early markers of pathological processes.
We aimed to determine the whole-brain network topologic organization of the functional connectome in a large cohort of drug-naïve Parkinson's disease (PD) patients using resting-state functional magnetic resonance imaging and to explore whether baseline connectivity changes may predict clinical progression.
One hundred and forty-seven drug-naïve, cognitively unimpaired PD patients were enrolled in the study at baseline and compared to 38 age- and gender-matched controls. Non-hierarchical cluster analysis using motor and non-motor data was applied to stratify PD patients into two subtypes: 77 early/mild and 70 early/severe. Graph theory analysis and connectomics were used to assess global and local topological network properties and regional functional connectivity at baseline. Stepwise multivariate regression analysis investigated whether baseline functional imaging data were predictors of clinical progression over 2 years.
At baseline, widespread functional connectivity abnormalities were detected in the basal ganglia, sensorimotor, frontal, and occipital networks in PD patients compared to controls. Decreased regional functional connectivity involving mostly striato-frontal, temporal, occipital, and limbic connections differentiated early/mild from early/severe PD patients. Connectivity changes were found to be independent predictors of cognitive progression at 2-year follow-up.
Our findings revealed that functional reorganization of the brain connectome occurs early in PD and underlies crucial involvement of striatal projections. Connectomic measures may be helpful to identify a specific PD patient subtype, characterized by severe motor and non-motor clinical burden as well as widespread functional connectivity abnormalities. © 2021 International Parkinson and Movement Disorder Society.
即使在脑萎缩发生之前，功能脑连接的改变也可能是可检测的，这表明它们有可能成为病理过程的早期标志物。
我们旨在使用静息态功能磁共振成像来确定大量未经药物治疗的帕金森病（PD）患者的功能连接组的全脑网络拓扑组织，并探索基线连接变化是否可以预测临床进展。
本研究共纳入 147 例未经药物治疗、认知无障碍的 PD 患者作为基线，并与 38 名年龄和性别匹配的对照组进行比较。使用运动和非运动数据的非层次聚类分析将 PD 患者分为 2 个亚型：77 例早期/轻度和 70 例早期/重度。图论分析和连接组学用于评估基线时的全局和局部拓扑网络特性以及区域功能连接。逐步多元回归分析调查了基线功能成像数据是否为 2 年临床进展的预测因素。
与对照组相比，PD 患者在基线时基底节、感觉运动、额叶和枕叶网络中存在广泛的功能连接异常。涉及大多数纹状体-额叶、颞叶、枕叶和边缘连接的区域性功能连接减少将早期/轻度与早期/重度 PD 患者区分开来。连接变化被发现是 2 年随访时认知进展的独立预测因子。
我们的研究结果表明，脑连接组的功能重组在 PD 早期发生，并为纹状体投射的重要参与提供了依据。连接组学测量可能有助于识别具有严重运动和非运动临床负担以及广泛功能连接异常的特定 PD 患者亚型。
