Abstract
OBJECTIVE: Early identification of cognitive impairment in neurodegenerative diseases like Alzheimer's disease (AD) is crucial. Neurofilament, a potential biomarker for neurological disorders, has gained attention. Our study aims to investigate the relationship between serum neurofilament light (sNfL) levels and cognitive function in elderly individuals in the United States. METHODS: This cross-sectional study analyzed data from participants aged 60 and above in the National Health and Nutrition Examination Survey (2013-2014). We collected sNfL levels, cognitive function tests, sociodemographic characteristics, comorbidities, and other variables. Weighted multiple linear regression models examined the relationship between ln(sNfL) and cognitive scores. Restricted cubic spline (RCS) visualization explored nonlinear relationships. The stratified analysis examined subgroups' ln(sNfL) and cognitive function association. RESULTS: The study included 446 participants (47.73% male). Participants with ln(sNfL) levels between 2.58 and 2.81 pg/mL (second quintile) performed relatively well in cognitive tests. After adjusting for multiple factors, ln(sNfL) levels were negatively correlated with cognitive function, with adjusted β (95% CI) as follows: immediate recall test (IRT): -0.763 (-1.301 to -0.224), delayed recall test (DRT): -0.308 (-0.576 to -0.04), animal fluency test (AFT): -1.616 (-2.639 to -0.594), and digit symbol substitution test (DSST): -2.790 (-4.369 to -1.21). RCS curves showed nonlinear relationships between ln(sNfL) and DRT, AFT, with inflection points around 2.7 pg/mL. The stratified analysis revealed a negative correlation between ln(sNfL) and cognition in specific subgroups with distinct features, with an interaction between diabetes and ln(sNfL). INTERPRETATION: Higher sNfL levels are associated with poorer cognitive function in the elderly population of the United States. sNfL shows promise as a potential biomarker for early identification of cognitive decline.