Association of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson's disease

Growing evidence highlights the roles of glymphatic system and peripheral inflammation in Parkinson's disease (PD). We evaluated their interrelationship and potential mechanisms contributing to motor symptoms using DTI-ALPS and inflammatory markers (leukocyte, lymphocyte, neutrophil counts, neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) in 134 PD patients (52 tremor-dominant [TD], 62 postural instability and gait difficulty [PIGD]) and 81 healthy controls (HC, 33 with inflammatory markers). PD exhibited lower DTI-ALPS than HC (1.43 ± 0.19 vs. 1.52 ± 0.21, p = 0.001). DTI-ALPS was negatively correlated with NLR, PLR, and neutrophils in PD (all p < 0.05) and with neutrophils in PIGD (β = -0.043, p = 0.048), and positively correlated with lymphocytes in TD (β = 0.105, p = 0.034). DTI-ALPS mediated the relationship between peripheral inflammation (NLR and neutrophils) and MDS-UPDRS III score in PD. Overall, glymphatic dysfunction correlates with peripheral inflammation and may mediate effects of inflammation on motor symptoms in PD, with distinct inflammation profiles between TD and PIGD.