Relationship between freezing of gait in Parkinson disease and locus coeruleus dysfunction: a neuromelanin-sensitive magnetic resonance imaging study.

Background: Preliminary scientific evidence suggests that freezing of gait (FoG) in patients with Parkinson disease (PD) is linked to noradrenergic dysfunction in the locus coeruleus (LC). However, definitive findings regarding the correlation between FoG occurrence and the LC are lacking. This study thus aimed to investigate the relationship between the FoG occurrence and LC degeneration in patients with PD by analyzing the signal characteristics of the LC in neuromelanin-sensitive magnetic resonance imaging (NM-MRI). Methods: This study enrolled 22 patients with PD and FoG, 24 patients with PD without FoG, and 13 matched healthy controls (HCs). All participants underwent magnetic resonance imaging (MRI) scanning and clinical assessments. The contrast-to-noise ratio (CNR) of LC was measured on NM-MRI images. We used two statistical models (model 1 and model 2) to screen and adjust for potential confounding factors and evaluated the independent relationship between LC's CNR and FoG. Results: The statistical models showed that except for the target factor FoG [model 1: β=0.127, 95% confidence interval (CI): 0.019-0.236, P=0.023; model 2: β=0.153, 95% CI: 0.019-0.287, P=0.026], rapid-eye-movement sleep behavior disorder (RBD) (model 1: β=0.182, 95% CI: 0.073-0.291, P=0.002; model 2: β=0.171, 95% CI: 0.048-0.294, P=0.008), and gender (model 1: β=0.150, 95% CI: 0.042-0.257, P=0.007) were independent factors associated with the CNR of the left LC. Among these, RBD had the greatest influence, followed by gender and FoG. Conclusions: Our findings indicated that the FoG is associated with noradrenergic dysfunction caused by LC degeneration.