Association of serum neurofilament light chain with cognitive impairment: findings from the National Health and Nutrition Examination Survey

Background: Serum Neurofilament Light chain (NfL) is a promising biomarker of neuronal damage, used to assess the extent of neuronal injury and neurodegeneration, and it is widely applied in the diagnosis of neurodegenerative disease and monitoring disease progression. This article aims to determine whether serum NfL associated with cognitive level. Methods: Using NHANES data, we conducted an analysis of cognitive test results for 450 adults aged 60 years and older and examined their correlation with serum NfL levels. When exploring the association between cognitive test scores and serum NfL levels, regression models and restricted cubic spline (RCS) regression models were employed to adjust for potential confounding factors. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key cognitive impairment factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve being built to evaluate its discriminatory power for cognitive impairment. Results: It was found that there is a strong positive correlation between serum NfL levels and both low total cognitive function (total-CF) OR: 1.028 (95%CI = 1.015-1.041 p < 0.001) and low Digit Symbol Substitution Test (DSST) OR: 1.026 (95%CI = 1.003-1.050, p = 0.027). Furthermore, using the RCS model, we observed a linear trend in the relationship between NfL and low total-CF. The nomogram model based on NfL identified by LASSO regression displayed a considerable predicative value for low total-CF, with an area under the curve [AUC = 85.6% (81.6-89.3%)]. Conclusion: There is a strong correlation between serum NfL levels and cognitive function, especially DSST, which reflects attention and information processing abilities, as well as overall cognitive function, but not memory and language fluency. Thus, NfL may serve as a serum biomarker for dementia monitoring.