Comparison of the prognostic value of cerebrospinal fluid and plasma neurofilament light in predicting longitudinal decline in white matter integrity among older adults

Abstract

AbstractBackgroundCerebrospinal fluid (CSF) neurofilament light (NFL) is a biomarker of neuroaxonal injury associated with cognitive decline, neurodegeneration, and white matter damage. Recent advances allow for plasma measurement of NFL, increasing accessibility of this biomarker. However, it is unknown if CSF and plasma NFL have similar prognostic value for predicting white matter damage. This study relates baseline CSF and plasma NFL concentrations to longitudinal change in white matter integrity in older adults.MethodVanderbilt Memory & Aging Project participants free of dementia at baseline (n=147, 72±6 years, 32% female) underwent baseline fasting lumbar puncture for CSF sampling and venous blood draw for plasma sampling. Participants completed serial 3T diffusion tensor imaging to assess white matter microstructural integrity at baseline, 18‐months, 3‐years, and 5‐years (follow‐up 4.3±1.3 years). Voxel‐wise linear mixed effects models with follow‐up time interaction terms related baseline CSF and plasma NFL separately to white matter microstructural trajectory, adjusting for baseline demographic and health variables, apolipoprotein E‐ε4 status, diagnosis, and follow‐up time. Follow‐up models tested interactions with diagnosis, amyloid‐β (Aβ), and phosphorylated tau (p‐tau).ResultCSF and plasma NFL were correlated (r=0.50, p<0.001). In the entire sample, CSF NFL related to faster white matter microstructural integrity decline in frontal, parietal, occipital, and subcortical regions (corrected p‐values<0.05). Plasma NFL related to faster white matter microstructural integrity decline in frontal and subcortical regions (corrected p‐values<0.05). CSF (largest β=5.7x10‐9) and plasma (largest β=3.1x10‐7) associations were similar in strength. CSF NFL interacted with diagnosis and Aβ (corrected p‐values<0.04), with associations driven by MCI and Aβ negative participants. Plasma NFL interacted with Aβ and p‐tau (corrected p‐values<0.04), with associations driven by Aβ and p‐tau negative participants.ConclusionAmong older adults, increased baseline CSF and plasma NFL concentrations predicted faster longitudinal decline in white matter integrity. While CSF NFL may relate to more widespread future white matter damage compared to plasma, plasma NFL could be an accessible biomarker for assessing future risk of white matter damage, particularly in individuals without Aβ or p‐tau pathology. CSF NFL may be a better prognostic biomarker in individuals with MCI, whereas plasma NFL has similar prognostic ability across diagnostic groups.