Alterations of cerebrospinal fluid flow dynamics in Parkinson’s disease

Cerebrospinal fluid (CSF) flow dynamics play a critical role in clearing pathological proteins from the brain, which may potentially influence the progression of neurodegenerative diseases. We aimed to investigate the alterations of CSF flow dynamics in patients with Parkinson's disease (PD). We employed the multiple low b-values diffusion magnetic resonance imaging combined with CSF-based spatial statistics to evaluate changes of CSF pseudo-diffusivity within ventricles, sulci, and cisterns in PD. We assessed the relationships between CSF pseudo-diffusivity and other indirect markers of glymphatic system, including the diffusion-tensor imaging along the perivascular space (DTI-ALPS) index, the volume of the choroid plexus and perivascular spaces. We explored the association between CSF pseudo-diffusivity and the integrity of the locus coeruleus (LC). A total of 44 patients and 48 healthy controls participated in the study. PD patients showed significantly reduced CSF pseudo-diffusivity within the ventricles and sulci, with no significant changes within the cisterns. Lower CSF pseudo-diffusivity was correlated with lower DTI-ALPS index. Furthermore, decreased CSF pseudo-diffusivity was correlated with LC degeneration. These findings suggested that PD exhibit reduced CSF flow dynamics within the ventricles and sulci. Furthermore, LC-norepinephrine system dysfunction may represent a potential mechanism and target for modulating CSF flow dynamics.