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Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

ABSTRACT: Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v₁ (2004-2009) and v₂ (2009-2013) plasma NfL exposure and ancillary sMRI data at v_scan (2011-2015, n = 179, mean v₁ to v_scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL_(v1) was associated with larger WMLV (both Log_e transformed), after 5-6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv₂ was linked to a 125 mm³ lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL_bayes). Among African American adults, NfL_v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC10524231 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

Beydoun May A MA Noren Hooten Nicole N Beydoun Hind A HA Weiss Jordan J Maldonado Ana I AI Katzel Leslie I LI Davatzikos Christos C Gullapalli Rao P RP Seliger Stephen L SL Erus Guray G Evans Michele K MK Zonderman Alan B AB Waldstein Shari R SR

Neurobiology of aging 20230502

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v<sub>1</sub> (2004-2009) and v<sub>2</sub> (2009-2013) plasma ...[more]

PMID: 37257406

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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:BackgroundTimely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT.MethodsWe enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3-6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage).ResultsOf the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03-4.08), T2 (OR, 2.08; 95% CI, 1.05-4.01), and T3 (OR, 3.94; 95% CI, 1.44-10.79) were independent predictors of death or disability at 90 days.ConclusionAmong patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.

Dataset Information

Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

Publications

Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.

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