Neutrophil‐to‐lymphocyte ratio and longitudinal cognitive performance in Parkinson's disease

Abstract

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.