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Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Biomarkers | Research article

Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women

Authors: May A. Beydoun, Nicole Noren Hooten, Jordan Weiss, Hind A. Beydoun, Sharmin Hossain, Michele K. Evans, Alan B. Zonderman

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Neurofilament light chain (NfL) is released into the blood during neuronal damage. NfL is linked to mortality in neurological disorders, remaining unexplored in population studies. We investigated whether initial (v1) and annualized change (δ) in plasma NfL can predict all-cause mortality in middle-aged dementia-free urban adults.

Methods

Longitudinal data were from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (HANDLS, mean agev1: 47.8 years, 42% male, 55.8% African American). Plasma NfL was measured prospectively at three visits. Analyses included Cox proportional hazards models for all-cause mortality risk and 4-way decomposition testing for interaction and mediation.

Results

Unlike men, women exhibited a direct association between δNfL (above vs. below median) and all-cause mortality risk in both the minimally (HR = 3.91, 95% CI 1.10–13.9, p = 0.036) and fully adjusted models (HR = 4.92, 95% CI 1.26–19.2, p = 0.022), and for δNfL (per unit increase) in the full model (HR = 1.65, 95% CI 1.04–2.61, p = 0.034). In both models, and among women, 1 standard deviation of NfLv1 was associated with an increased all-cause mortality risk (reduced model: HR = 2.01, 95% CI 1.24–3.25, p = 0.005; full model: HR = 1.75, 95% CI 1.02–2.98, p = 0.041). Only few interactions were detected for cardio-metabolic risk factors. Notably, NfLv1 was shown to be a better prognostic indicator at normal hsCRP values among women, while HbA1c and δNfL interacted synergistically to determine mortality risk, overall.

Conclusions

These findings indicate that plasma NfL levels at baseline and over time can predict all-cause mortality in women and interacts with hsCRP and HbA1c to predict that risk.
Appendix
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Metadata
Title
Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women
Authors
May A. Beydoun
Nicole Noren Hooten
Jordan Weiss
Hind A. Beydoun
Sharmin Hossain
Michele K. Evans
Alan B. Zonderman
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Biomarkers
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02425-x

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