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

Abstract

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-naïve 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.

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

“…A recent prospective study found that individuals with gastrointestinal symptoms that required a gastrointestinal endoscopy, but with a finding of histologically normal mucosa or nonspecific inflammation, had an increased subsequent risk of developing Alzheimer's or Parkinson diseases compared with the population references [70]. In line with this are previously published studies in which lymphocyte count and different patterns of neutrophil-to-lymphocyte or platelet-to-lymphocyte ratio were associated not only with PD, but also with MCI in PD or MSA patients, thus reflecting the inflammatory process in α-synucleinopathies [71,72].…”

The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study

“…In contrast, a case–control study by Sağlam Aykut et al (2018) reported a negative correlation between cognitive function and the NLR. In addition, other studies have shown that NLR values were significantly lower in Parkinson’s disease patients with MCI compared with those without MCI ( Contaldi et al, 2022 ). The differences in results may be due to differences in sample size, age, disease, and scales that measure cognitive function.…”

The neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and neutrophil-to-high-density-lipoprotein ratio are correlated with the severity of Parkinson’s disease

“…Additionally, markers related to peripheral blood neutrophils can predict a decrease in executive function in patients with AD ( 54 ). A recent study indicated that an elevated NLR is associated with cognitive impairment in PD patients ( 55 ). Therefore, we explored the potential of the NLR as a biomarker.…”