Red cell distribution width-to-albumin ratio and serum neurofilament light chain: A population-based study

Neurofilament light chain (NfL) is a blood biomarker of neuronal injury in inflammatory and neurodegenerative disorders. The red cell distribution width-to-albumin ratio (RAR) reflects systemic inflammation and nutritional status. This study investigated whether higher RAR is associated with higher serum NfL (sNfL) in a general adult population.

Data from 1750 adults who participated in the 2013-2014 National Health and Nutrition Examination Survey were analysed. RAR was calculated as red cell distribution width (%) divided by serum albumin (g/dL). sNfL was measured using an automated Atellica chemiluminescent immunoassay. Participants were grouped into RAR quartiles. Survey-weighted multivariable linear regression and restricted cubic spline (RCS) models assessed associations between RAR and log-transformed sNfL, adjusting for demographic, socioeconomic, lifestyle and clinical factors.

Each unit increase in RAR was associated with higher sNfL in unadjusted analysis, and this association remained significant in partially and fully adjusted models. Compared with participants in the lowest quartile, those in the highest RAR quartile had higher sNfL, with a significant trend across quartiles. RCS analysis showed a non-linear but monotonic increase in log-transformed sNfL with higher RAR (P for non-linearity = 0.020). Associations varied by race/ethnicity, body mass index and diabetes status.

Higher RAR is associated with higher sNfL in US adults. This epidemiological association suggests that inflammation/nutritional status may relate to neuroaxonal injury. Longitudinal studies are needed to establish temporality and assess prognostic value before any clinical application.