Associations of plasma neurofilament light chain and progranulin with frailty in older adults

Lu, Wan‐Hsuan; Giudici, Kelly Virecoulon; Guyonnet, Sophie; Aggarwal, Geetika; Nguyen, Andrew D.; Morley, John E.; Vellas, Bruno; Barreto, Philipe de Souto

doi:10.1111/jgs.17604

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…Indeed, pathophysiological mechanisms of cachexia are related to a serious illness such as cancer and are not considered to share neurological features [33]. Regarding frailty, Lu et al were unable to find an association between NF-L and frailty in older adults although the choice of the covariates has been commented on by other peers [34][35][36]. Therefore, assessing NF-L in other muscle wasting syndrome seems relevant, and NF-L might represent an interesting opportunity A second positioning of NF-L as a biomarker of sarcopenia could be the identification of sarcopenia severity or the identification of subjects with lower performance tests.…”

Section: Discussionmentioning

confidence: 99%

Neurofilament-light chains (NF-L), a biomarker of neuronal damage, is increased in patients with severe sarcopenia: results of the SarcoPhAge study

et al. 2023

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Background As clinical tests, such as gait speed, require nervous system integrity to be performed properly, sarcopenia shares features with neurological diseases. Neurofilament light chains (NF-L) are now used as a blood-biomarker of neuronal damage, and its expression might be altered in sarcopenia. We aimed to assess NF-L concentrations in a large cohort of older individuals screened for sarcopenia. Methods The SarcoPhAge cohort is a Belgian cohort of 534 community-dwelling older adults with an ongoing 10-year follow-up. Sarcopenia diagnosis was established at inclusion according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was evaluated with a hydraulic hand dynamometer, appendicular lean mass by Dual-Energy X-ray Absorptiometry (DXA) and physical performance by the Short Physical Performance Battery (SPPB). NF-L was measured on all available sera collected at the time of inclusion (n = 409) using SiMoA technology (Quanterix°). Results In the multivariate model, NF-L was associated with performance tests such as gait speed (p < 0.0001) and SPPB scores (p = 0.0004). An association was also observed with muscle strength (p = 0.0123) and lean mass (p = 0.0279). In the logistic regression model, NF-L was an independent predictor of severe sarcopenia (p = 0.0338; OR = 20.0; 95% CI 1.39–287.7) with satisfactory diagnostic accuracy (AUC: 0.828) and subjects with an SPPB score ≤ 8 had higher odds of having increased NF-L (p < 0.0001; OR = 23.9; 95% CI 5.5–104). Conclusions These data highlight the potential for using NF-L to investigate the pathophysiology of sarcopenia severity and the neurological features associated with performance tests. However, these results need to be confirmed with other cohorts in different settings.

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Section: Discussionmentioning

confidence: 99%

Neurofilament-light chains (NF-L), a biomarker of neuronal damage, is increased in patients with severe sarcopenia: results of the SarcoPhAge study

et al. 2023

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“…Neurofilament light chain protein is part of the neuronal cytoskeleton and increased levels in the CSF reflect axonal damage and degeneration 47 48. It is not disease-specific and has been used as a marker of neuronal injury in neurodegenerative disease,49 multiple sclerosis,47 cerebrovascular disease48 and traumatic brain injury 50. A recent study in patients with SLE and in patients with Sjögren’s syndrome reported increased CSF levels of neurofilament light chain protein in association with cognitive impairment 51.…”

Section: Discussionmentioning

confidence: 99%

Role of autoantibodies and blood–brain barrier leakage in cognitive impairment in systemic lupus erythematosus

et al. 2022

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ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage.MethodsConsecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers.ResultsThere were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8–24 years) vs 15 (2–16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage.ConclusionsExtensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

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“…We appreciate the comments from Kaloostian and Shil 1 regarding our work on plasma neurofilament light chain (NfL), progranulin (PGRN), and frailty using data from the Multidomain Alzheimer Preventive Trial (MAPT). 2 As they suggest, several variables might be introduced as covariates due to their potential influences on either NfL concentrations (i.e., impaired kidney function and COVID-19 inflection) or muscle function (i.e., under the treatment of angiotensinconverting enzyme inhibitor [ACEI] and vitamin D insufficiency).…”

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Reply to: Comment on: The associations of plasma neurofilament light chain and progranulin with frailty in older adults

Vellas

Barreto

2022

J American Geriatrics Society

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Associations of plasma neurofilament light chain and progranulin with frailty in older adults

Cited by 6 publications

References 38 publications

Neurofilament-light chains (NF-L), a biomarker of neuronal damage, is increased in patients with severe sarcopenia: results of the SarcoPhAge study

Neurofilament-light chains (NF-L), a biomarker of neuronal damage, is increased in patients with severe sarcopenia: results of the SarcoPhAge study

Role of autoantibodies and blood–brain barrier leakage in cognitive impairment in systemic lupus erythematosus

Reply to: Comment on: The associations of plasma neurofilament light chain and progranulin with frailty in older adults

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