MRI index of glymphatic system mediates the influence of locus coeruleus on cognition in Parkinson's disease

INTRODUCTION: Although locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD. METHODS: In this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNR_LC). RESULTS: The ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNR_LC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNR_LC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNR_LC and the MoCA score in PD subjects. CONCLUSION: The ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD.