Dataset Information

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

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 age_v1: 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 NfL_v1 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, NfL_v1 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.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC9190073 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Beydoun May A MA Noren Hooten Nicole N Weiss Jordan J Beydoun Hind A HA Hossain Sharmin S Evans Michele K MK Zonderman Alan B AB

BMC medicine 20220613 1

<h4>Background</h4>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 (v<sub>1</sub>) and annualized change (δ) in plasma NfL can predict all-cause mortality in middle-aged dementia-free urban adults.<h4>Methods</h4>Longitudinal data were from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study ...[more]

PMID: 35692046

Similar Datasets

Project description:BackgroundPlasma neurofilament light chain (NfL) is a novel biomarker for age-related neurodegenerative disease. We tested whether NfL may be linked to cardiometabolic risk factors, including BMI, the allostatic load (AL) total score (ALtotal), and related AL continuous components (ALcomp). We also tested whether these relations may differ by sex or by race.MethodsWe used data from the HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span) study [n = 608, age at visit 1 (v1: 2004-2009): 30-66 y, 42% male, 58% African American] to investigate associations of initial cardiometabolic risk factors and time-dependent plasma NfL concentrations over 3 visits (2004-2017; mean ± SD follow-up time: 7.72 ± 1.28 y), with outcomes being NfLv1 and annualized change in NfL (δNfL). We used mixed-effects linear regression and structural equations modeling (SM).ResultsBMI was associated with lower initial (γ01 = -0.014 ± 0.002, P < 0.001) but faster increase in plasma NfL over time (γ11 = +0.0012 ± 0.0003, P < 0.001), a pattern replicated for ALtotal. High-sensitivity C-reactive protein (hsCRP), serum total cholesterol, and resting heart rate at v1 were linked with faster plasma NfL increase over time, overall, while being uncorrelated with NfLv1 (e.g., hsCRP × Time, full model: γ11 = +0.004 ± 0.002, P = 0.015). In SM analyses, BMI's association with δNfL was significantly mediated through ALtotal among women [total effect (TE) = +0.0014 ± 0.00038, P < 0.001; indirect effect = +0.00042 ± 0.00019, P = 0.025; mediation proportion = 30%], with only a direct effect (DE) detected among African American adults (TE = +0.0011 ± 0.0004, P = 0.015; DE = +0.0010 ± 0.00048, P = 0.034). The positive associations between ALtotal/BMI and δNfL were mediated through increased glycated hemoglobin (HbA1c) concentrations, overall.ConclusionsCardiometabolic risk factors, particularly elevated HbA1c, should be screened and targeted for neurodegenerative disease, pending comparable longitudinal studies. Other studies examining the clinical utility of plasma NfL as a neurodegeneration marker should account for confounding effects of BMI and AL.

Project description:ObjectivesTo determine the extent to which educational inequalities in relation to mortality widened in Norway during 1960-2000 and which causes of death were the main drivers of this disparity.DesignNationally representative prospective study.SettingFour cohorts of the Norwegian population aged 45-64 years in 1960, 1970, 1980, and 1990 and followed up for mortality over 10 years.Participants359 547 deaths and 32 904 589 person years.Main outcome measuresAll cause mortality and deaths due to cancer of lung, trachea, or bronchus; other cancer; cardiovascular diseases; suicide; external causes; chronic lower respiratory tract diseases; or other causes. Absolute and relative indices of inequality were used to present differences in mortality by educational level (basic, secondary, and tertiary).ResultsMortality fell from the 1960s to the 1990s in all educational groups. At the same time the proportion of adults in the basic education group, with the highest mortality, decreased substantially. As mortality dropped more among those with the highest level of education, inequalities widened. Absolute inequalities in mortality denoting deaths among the basic education groups minus deaths among the high education groups doubled in men and increased by a third in women. This is equivalent to an increase in the slope index of inequality of 105% in men and 32% in women. Inequalities on a relative scale widened more, from 1.33 to 2.24 among men (P=0.01) and from 1.52 to 2.19 among women (P=0.05). Among men, absolute inequalities mainly increased as a result of cardiovascular diseases, lung cancer, and chronic lower respiratory tract diseases. Among women this was mainly due to lung cancer and chronic lower respiratory tract diseases. Unlike the situation in men, absolute inequalities in deaths due to cardiovascular causes narrowed among women. Chronic lower respiratory tract diseases contributed more to the disparities in inequalities among women than among men.ConclusionAll educational groups showed a decline in mortality. Nevertheless, and despite the fact that the Norwegian welfare model is based on an egalitarian ideology, educational inequalities in mortality among middle aged people in Norway are substantial and increased during 1960-2000.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets