Morpho-functional correlates of gait impairment in early Parkinson's disease patients: insights from a multimodal path modeling framework.

OBJECTIVE

To deepen the underlying pathophysiology of gait impairment in early-stage Parkinson's disease (PD) through a multimodal assessment, including MR-based brainstem morphometry and EEG functional connectivity (FC).

METHODS

73 PD patients and 60 healthy controls (HC) were included. The MR Parkinsonism Index (MRPI) was calculated for each subject. FC was measured using HD-EEG in θ-α-β-low-γ-high-γ bands. Partial Least Squares Path Modeling (PLS-PM) was used to explore the causal relationships between MRPI, FC, and clinical data.

RESULTS

MRPI was higher in PD than HC (p = 0.001) and correlated with MDS-UPDRS-III gait subscore (r = 0.54,p < 0.001). α-FC was significantly lower in PD than HC (t = -5.4,p < 0.001). α-FC in PD was negatively correlated with both MRPI (r = -0.31,p = 0.007) and gait subscore (r = -0.31,p = 0.007). PLS-PM revealed MRPI's negative direct effect on α-FC (-0.59,p < 0.001) and significant positive total effect on gait performance (0.53,p < 0.001), partially mediated by α-FC (0.19, p = 0.006). Additionally, α-FC had a direct negative impact on gait performance (-0.33,p = 0.004).

CONCLUSIONS

The effect of MRPI on gait performance, partially mediated by α-FC, highlights a dual pattern in which brainstem structural alterations show an association with gait impairment both directly and indirectly through their relationship with cortical functional disruptions.

SIGNIFICANCE: These findings support a multimodal framework for understanding and addressing gait disorders in PD, potentially opening avenues for personalized treatment.