The Mediating Effect of Carotid Plaque Vulnerability in the Association Between NMLR and Cognitive Impairment

Objective: This study aims to explore the mediating role of carotid plaque vulnerability in the association between the neutrophil-plus-monocyte-to-lymphocyte ratio (NMLR) and cognitive impairment in patients with carotid artery stenosis (CAS). Methods: A total of 211 CAS patients who underwent carotid endarterectomy (CEA) were retrospectively enrolled and divided into stable plaque (n = 104) and vulnerable plaque (n = 107) groups based on postoperative pathological examination. Clinical data, laboratory indicators (including neutrophil, monocyte, and lymphocyte counts), and Montreal Cognitive Assessment (MoCA) scores were collected. Multivariate logistic regression and mediation analysis were used to evaluate the relationships among NMLR, plaque vulnerability, and cognitive function. Results: Patients with vulnerable plaques had significantly higher NMLR and lower MoCA scores compared to those with stable plaques (both P < 0.001). Multivariate analysis identified NMLR as an independent risk factor for both plaque vulnerability (OR = 4.51, P < 0.001) and cognitive impairment (OR = 4.22, P < 0.001). Mediation analysis revealed that plaque vulnerability partially mediated the association between NMLR and cognitive function, accounting for 10.58% of the total effect. The area under the ROC curve of NMLR for predicting plaque vulnerability was 0.80. Conclusion: NMLR is significantly associated with carotid plaque vulnerability and cognitive impairment. Plaque vulnerability mediates part of the effect of NMLR on cognitive function, suggesting that NMLR may serve as a novel inflammatory biomarker for assessing plaque stability and cognitive risk in CAS patients, providing a potential target for early intervention in vascular cognitive impairment.