Increased blood-brain barrier permeability is associated with dysfunctional α band connectivity in early-stage Parkinson's disease.

The blood-brain barrier (BBB) is disrupted in Parkinson's disease (PD); however, whether its alteration precedes neuroinflammation and central synucleinopathy or results from these conditions is still unclear. In this study, we aimed to explore how alterations in BBB permeability may relate to disruptions in functional connectivity (FC) across cortical networks using HD-EEG and combining a network-based approach with Machine Learning (ML). This study involved 68 early-stage PD patients and 62 sex- and age-matched healthy controls. Albumin Index (Qalb), obtained by albumin in the cerebrospinal fluid (CSF) divided by the amount in the plasma, was assessed in all PD patients. EEG data were recorded with a 64-channel EEG system. Source reconstruction based on personal MRI was used to identify brain activity. Cortico-cortical FC was analyzed based on the weighted phase-lag index (wPLI) in θ-α-β-low γ bands. Network-based statistic (NBS) was used to compare FC between HCs and PD and to study the relationship between FC and BBB permeability, as measured by Qalb. PD patients exhibited a hypoconnected network at α bands and a hyperconnected network at β band compared to HCs. We observed a negative relation between Qalb and α-FC (network t = 3.6, p = 0.008). Regions with higher degrees were part of the prefrontal, limbic, and temporal lobes. No significant correlations between Qalb and clinical features or neurodegenerative markers were found. Increased BBB permeability in early-stage PD is associated with frequency- and region-specific abnormal cortical FC, supporting the hypothesis that alteration of BBB may accelerate PD pathology, contributing to a more malignant disease phenotype.