Mediating role of white blood cells in the relationship between the advanced lung cancer inflammation index and serum neurofilament light chain levels: A study based on NHANES 2013–2014 data

This study aimed to explore the mediating role of white blood cell (WBC) count in the relationship between the advanced lung cancer inflammation index (ALI) and serum neurofilament light chain (sNfL) levels. We conducted a cross-sectional analysis of 1725 adult participants from the 2013 to 2014 National Health and Nutrition Examination Survey. ALI was calculated as body mass index × serum albumin/neutrophil-to-lymphocyte ratio, and participants were categorized into quartiles based on ALI distribution. Associations among ALI, WBC count, and sNfL levels were examined using weighted multivariable linear regression, nonlinear curve fitting, and mediation analysis. Higher ALI values were significantly associated with lower sNfL concentrations (β = -0.04 per unit increase; 95% confidence interval [CI]: -0.06--0.02; P = .0007), demonstrating a clear dose-response pattern across ALI quartiles. A nonlinear relationship was identified, with a threshold effect at an ALI value of 71.64. Below this threshold, ALI showed a stronger inverse association with sNfL (β = -0.14; 95% CI: -0.21--0.08; P < .0001), which attenuated above the threshold (β = -0.01; P = .63). WBC count partially mediated the association between ALI and sNfL, accounting for 21.04% of the total effect (95% CI: 6.85-43.18%; P = .006). ALI is inversely associated with serum sNfL levels in the general United States adult population, with WBC count acting as a significant mediator. Clinically, these findings suggest that ALI, a readily available composite marker of systemic inflammation and nutritional status, may help identify individuals at higher risk of neuroaxonal injury, thereby supporting its potential utility in population-level neurodegenerative risk stratification and early preventive assessment. Further longitudinal studies are warranted to confirm these associations and clarify their prognostic implications.