Objective: To investigate whole-brain network topologic organization in a large cohort of drug-naïve Parkinson’s disease (PD) patients using resting-state functional MRI (rs-fMRI); and to determine whether early functional connectivity measures may predict disease progression overtime.

Background: 147 drug-naive PD patients were consecutively enrolled. Motor, non-motor and neuropsychological assessments as well as rs-fMRI were performed at baseline. 38 age- and sex-matched controls were also enrolled in the study. Non-hierarchical cluster analysis using motor, non-motor and neuropsychological data were applied to stratify PD patients in two subtypes: 77 patients were grouped as “early/mild” and 70 as “early/severe”. After the baseline assessments, all patients started a dopaminergic replacement therapy accordingly to current international guidelines and were followed for an observation period, lasting a maximum of 24 months, with a clinical follow-up every 12-months.

Method: Graph analysis and connectomics were used to assess global and local topological network properties and regional functional connectivity (FC) at baseline in both PD patients and controls. Multivariate linear and logistic regressions investigated whether functional imaging data at baseline were predictors of motor impairment and levodopa requirement over a 2-year period.

Results: At baseline, “early/mild” PD patients showed a preserved global functional brain architecture compared to controls. “Early/severe” PD patients showed altered functional topological properties within the basal ganglia network compared to “early/mild” PD patients. Widespread FC abnormalities were detected in several networks encompassing basal ganglia, sensorimotor and occipital areas in PD patients compared to controls. Decreased FC involving mainly striato-frontal, striato-temporal and limbic connections differentiated “early-mild” from “early-severe” PD patients. FC abnormalities at baseline were found to be an independent predictor of levodopa requirement over 2-years.

Conclusion: Our findings revealed that a specific subtype of PD patients, characterized by severe motor and non-motor burden as well as widespread FC abnormalities, may be identified at the time of diagnosis. We hypothesize that this FC pattern may reflect the presence of more diffuse neuropathological changes. Combined clinical and neuroimaging tools are promising to stratify risk of PD progression overtime.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-brain-connectome-in-drug-naive-parkinsons-disease-patients/