Association between depressive symptoms and cognitive function in the older population, and the mediating role of neurofilament light chain: Evidence from NHANES 2013–2014

This study aimed to investigate the potential mediating role of the neurofilament light chain (NfL) level between depressive symptoms and cognitive function in older population. A total of 495 adults (age ≥60 years) from the National Health and Nutrition Examination Survey (NHANES) participated in this study. Cognitive function was assessed using a combination of the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Digit Symbol Substitution Test (DSST). Word List Learning Test. Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data on serum NfL(sNfL) were collected. Multiple linear regressions and mediation analysis were utilized to examine the associations. After adjusting for potential confounding factors, the proportions mediated by the sNfL level between depressive symptoms and cognitive function was 19.65 %. The indirect effect mediated by the sNfL level between depressive symptoms and cognitive function was significant (β[95 % CI]:-0.0089 [−0.0191, −0.0017],p = 0.040), while the direct effect in the absence of sNfL was non-significant (β[95 % CI]: −0.0365 [−0.0739 0.0008],p = 0.055). This is an explorative cross-sectional study with its limits in generalizability and ability to establish definitive causal associations. The results should be interpreted with caution due to the constraints imposed by the characteristics of the population with a relatively low overall level of depressive symptoms. The sNfL level, depressive symptoms, and cognitive decline are interconnected, and the sNfL level could mediate the relationship between depressive symptoms and cognitive decline among older adults.