Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson's disease

Dysfunction of the glymphatic system, an intracranial clearance pathway that drains misfolded proteins, has been implicated in the onset of Parkinson's disease (PD). Recently, the coupling strength of global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics have been suggested to be an indicator of glymphatic function. Using resting-state functional magnetic resonance imaging (MRI), we quantified gBOLD-CSF coupling strength as the cross-correlation between baseline gBOLD and CSF inflow signals to evaluate glymphatic function and its association with the clinical manifestations of PD. We found that gBOLD-CSF coupling in drug-naïve PD patients was significantly weaker than that in normal controls, but significantly stronger in patients less affected by sleep disturbances than in those more affected by sleep disturbances, based on the PD sleep scale. Furthermore, we collected longitudinal data from patients and found that baseline gBOLD-CSF coupling negatively correlated with the rate of change over time, but positively correlated with the rate of change in UPDRS-III scores. In conclusion, severe gBOLD-CSF decoupling in PD patients may reflect longitudinal motor impairment, thereby providing a potential marker of glymphatic dysfunction in PD.