Altered functional topology related to the development of wearing-off in Parkinson's disease

Wearing-off (WO) is the most common medicine-related complication that develops in later stage of Parkinson's disease (PD), whereas the underlying mechanism still remains unknown. Here, we aimed to decipher the mechanism underlying the WO in PD patients.

Twenty-six PDWO (PD with WO), 26 PDnW (PD without WO) and 34 healthy controls were included and functional and structural magnetic resonance imaging (MRI) were employed. Functional network was constructed based on the matrix of each subject's functional images and attributes of functional topology (e.g., global and local metrics) were calculated. Intergroup differences in white matter and grey matter were compared to potentially explore the structural abnormalities. Partial correlation analysis was performed to demonstrate the relationships between the altered imaging findings and clinical variables.

Wearing-off in PD patients was independently associated with levodopa equivalent daily dose (LEDD) /weight. Functional degree centrality (DC) having negative correlation with WO severity was significantly decreased in supramarginal gyrus in PDWO. Functional DC in precentral gyrus was significantly lower in PDnW compared with healthy controls, which was correlated with dopaminergic medication profiles. No apparent evidence about structural abnormality was found in PDWO and PDnW patients.

The occurrence of wearing-off in PD patients was independently associated with LEDD/weight. The functional disruption in supramarginal gyrus might reflect the development of wearing-off, and we speculated the attenuation of levodopa related plasticity in precentral gyrus had an association with the susceptibility of wearing-off in PD patients. Further research are needed to validate and extend these preliminary findings.