Longitudinal brain connectivity changes and clinical evolution in Parkinson’s disease

帕金森病 认知 疾病 神经科学 生物标志物 纵向研究 功能连接 静息状态功能磁共振成像 医学 物理医学与康复 心理学 内科学 病理 生物 生物化学
作者
Massimo Filippi,Silvia Basaia,Elisabetta Sarasso,Tanja Stojković,Iva Stanković,Andrea Fontana,Aleksandra Tomić,Noemi Piramide,Elka Stefanova,Vladana Marković,Vladimir Kostić,Federica Agosta
出处
期刊:Molecular Psychiatry [Springer Nature]
卷期号:26 (9): 5429-5440 被引量:53
标识
DOI:10.1038/s41380-020-0770-0
摘要

Longitudinal connectivity studies might guide our understanding of the underlying neurodegenerative processes. We report the results of a longitudinal study in patients at different stages of Parkinson's disease (PD), who performed motor and non-motor evaluations and serial resting state (RS) functional MRI (fMRI). Cluster analysis was applied to demographic and clinical data of 146 PD patients to define disease subtypes. Brain network functional alterations were assessed at baseline in PD relative to 60 healthy controls and every year for a maximum of 4 years in PD groups. Progression of brain network changes were compared between patient clusters using RS fMRI. The contribution of network changes in predicting clinical deterioration was explored. Two main PD clusters were identified: mild PD (86 patients) and moderate-to-severe PD (60 patients), with the latter group being older and having earlier onset, longer PD duration, more severe motor, non-motor and cognitive deficits. Within the mild patient cluster, two clinical subtypes were further identified: mild motor-predominant (43) and mild-diffuse (43), with the latter being older and having more frequent non-motor symptoms. Longitudinal functional connectivity changes vary across patients in different disease stages with the coexistence of hypo- and hyper-connectivity in all subtypes. RS fMRI changes were associated with motor, cognitive and non-motor evolution in PD patients. Baseline RS fMRI presaged clinical and cognitive evolution. Our network perspective was able to define trajectories of functional architecture changes according to PD stages and prognosis. RS fMRI may be an early biomarker of PD motor and non-motor progression.
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