Lymphocyte Count and Neutrophil-to-Lymphocyte Ratio Are Associated with Mild Cognitive Impairment in Parkinson’s Disease: A Single-Center Longitudinal Study

Lymphocyte count and neutrophil-to-lymphocyte ratio (NLR) may represent useful biomarkers of Parkinson's disease (PD), but their role in PD-related mild cognitive impairment (MCI) has not been fully elucidated. The present study aimed to confirm whether these immunological measures can discriminate PD patients from healthy controls (HC) and establish their feasibility as prognostic biomarkers of MCI in PD. Immunological data at baseline were analyzed in 58 drug-naive PD patients and 58 HC matched 1:1 for age, sex, and cardiovascular comorbidities. We selected a subgroup of 51 patients from this initial cohort who underwent longitudinal neuropsychological assessments through the Addenbrooke's Cognitive Examination Revised (ACE-R) test. We considered the last examination available to analyze the relationship between ACE-R test scores and immunological measures. We found that lymphocyte count was lower and NLR higher in PD than HC (p = 0.006, p = 0.044), with AUC = 0.649 and 0.608, respectively. Secondly, in PD-MCI there were significantly higher levels of circulating lymphocytes (p = 0.002) and lower NLR (p = 0.020) than PD with normal cognitive status (PD-NC). Correlations between lymphocyte count and ACE-R total score and memory subitem (r = -0.382, p = 0.006; r = -0.362, p = 0.01), as well as between NLR and ACE-R total score and memory subitem (r = 0.325, p = 0.02; r = 0.374, p = 0.007), were also found. ROC curve analysis showed that lymphocyte count and NLR displayed acceptable discrimination power of PD-MCI with AUC = 0.759 and 0.691, respectively. In conclusion, we suggest that an altered peripheral immune phenotype could foster cognitive decline development in PD, thus opening the possibility of immune-targeting strategies to tackle this disabling non-motor feature.