1173 Association of Peripheral Blood Neutrophil-Lymphocyte Ratio with Motor and Cognitive Function in Isolated REM Sleep Behavior Disorder

Abstract Introduction Emerging evidence suggests that subtle immune alterations may precede the clinical onset of Parkinson’s disease (PD). The neutrophil–lymphocyte ratio (NLR), a readily obtainable marker of systemic inflammation, has been proposed as a potential indicator of prodromal pathology. We investigated whether peripheral neutrophil and lymphocyte indices are altered in individuals with isolated REM sleep behavior disorder (iRBD), a well-established prodromal stage of α-synucleinopathy, and whether these markers relate to early motor or cognitive features. Methods We examined participants enrolled in the Parkinson’s Progression Markers Initiative who met criteria for iRBD (n=116), and we compared them with age-matched healthy controls (n=284). Motor function was quantified using the MDS-UPDRS part III. Cognitive performance was evaluated across multiple domains using standardized neuropsychological assessments. Group differences in blood markers and their associations with clinical measures were analyzed with appropriate covariate adjustments and false discovery rate correction. Results Individuals with iRBD showed significantly lower lymphocyte counts compared with controls (P< 0.001), while neutrophil counts were comparable between groups (P=0.749). Consequently, NLR values were elevated in iRBD (P=0.008). Within the iRBD cohort, higher NLR—driven primarily by lower lymphocyte levels—was associated with greater motor impairment on the MDS-UPDRS part III after correction for multiple comparisons (Q=0.011). This association was not influenced by additional prodromal features, and no significant relationships were observed between immune markers and cognitive test performance. Conclusion These findings suggest that immune dysregulation characterized by elevated NLR is detectable in iRBD and is related to subtle motor dysfunction before the emergence of overt PD. Whether lymphocyte-based inflammatory markers hold prognostic value for phenoconversion to Parkinson’s disease warrants further longitudinal investigation. Support (if any)