Neutrophil-to-lymphocyte ratio is associated with cognitive performance in isolated REM sleep behavior disorder

Background Isolated REM sleep behavior disorder (iRBD) is the prodromal phase of α-synucleinopathies. Peripheral inflammation, indexed by the neutrophil-to-lymphocyte ratio (NLR), has been associated with cognitive dysfunctions in established α-synucleinopathies, but its role in prodromal stages remains unclear. Based on this background, we investigated the association between NLR and cognitive performance in individuals with iRBD. Methods We analyzed cross-sectional data from 371 individuals with iRBD and 262 controls from the Parkinson's Progression Markers Initiative. Baseline assessments included demographic and clinical variables, NLR derived from peripheral blood counts, and a comprehensive neuropsychological battery. Cross-sectional associations between NLR and cognitive performance were examined using univariate and multivariable linear regression models adjusted for age, sex, education, APOE ε4 status, and motor severity. Longitudinal analyses were conducted in a subgroup of 38 iRBD participants followed for 2–5 years to evaluate the relationship between baseline NLR and changes in cognitive performance over time. Results At baseline, NLR was inversely associated with long-term verbal memory in the iRBD group, but not in the control group. In the iRBD group, higher NLR was also associated with worsening of visuospatial abilities, processing speed, and semantic fluency over time. Conclusion These findings suggest that peripheral inflammation may be involved in early mechanisms of cognitive vulnerability in iRBD. Further studies are needed to clarify whether this represents an epiphenomenon of the underlying pathology or plays an active role in disease progression.