Abstract
OBJECTIVE: Previous studies have suggested a link between peripheral inflammation and cognitive outcomes in the general population and individuals with Parkinson's disease (PD). We sought to test the association between peripheral inflammation, measured by the neutrophil-to-lymphocyte ratio (NLR), cognitive performance, and mild cognitive impairment (MCI) status in individuals with PD. METHODS: A retrospective, longitudinal analysis was carried out using data from the Parkinson's Progression Markers Initiative (PPMI), including 422 participants with PD followed over 5 years. Cognitive performance was assessed using a neuropsychological battery including the Montreal Cognitive Assessment (MoCA) and tests of verbal learning, visuospatial function, processing speed, and executive function. Mixed-effect regression models were used to analyze the association between NLR, cognitive performance, and MCI status, controlling for age, sex, education, APOE genotype, and motor severity. RESULTS: There was a negative association between NLR and MoCA, even after adjusting for covariates (b = -0.12, p = 0.033). MoCA scores for individuals in the high NLR category exhibited a more rapid decline over time compared to the low NLR group (b = -0.16, p = 0.012). Increased NLR was associated with decreased performance across all cognitive domains. However, NLR was not associated with MCI status over 5 years of follow-up. INTERPRETATION: This study demonstrates a link between elevated NLR and cognitive performance in PD, but not with MCI status over 5 years. This suggests that NLR is more strongly associated with day-to-day cognitive performance than with incident MCI, but this requires further study in more heterogeneous cohorts.