ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1645290
This article is part of the Research TopicAdvancing personalized diagnosis and treatment in Parkinson's Disease: Integrating biomarkers, neuroimaging, and artificial intelligenceView all 15 articles
Neurofilament Light Chain Concentration Mediates the Association Between Regional Cortical Thickness and Parkinson's Disease with Excessive Daytime Sleepiness
Provisionally accepted
- The First Affiliated Hospital of Kunming Medical University, Kunming, China
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Background: Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson's disease (PD) that negatively impacts quality of life. Although biomarkers of brain structure, function, and neurodegeneration have been studied, their interactions in EDS remain unclear. This study explores the relationship between cortical thickness, functional connectivity (FC), and plasma neurofilament light chain (NfL) levels in PD-EDS.underwent structural MRI and resting-state FC analysis, with regions of cortical atrophy serving as regions of interest (ROIs). Plasma NfL levels were quantified using high-sensitivity Single Molecule Array (SiMoA™). Mediation analysis was conducted to explore the interplay between NfL levels, neuroimaging markers, and EDS severity, assessed by the Epworth Sleepiness Scale (ESS).Results: PD-EDS patients exhibited significant cortical thinning in the left supramarginal gyrus (SMG) and right postcentral region (PoCR), along with weakened FC between the left SMG and left PoCR, and between the right PoCR and left inferior frontal gyrus (all p < 0.05). Plasma NfL levels were significantly higher in PD-EDS patients than in those without EDS (p = 0.004) and mediated the relationship between left SMG thickness and EDS severity.Plasma NfL levels mediate the association between cortical thinning in the left SMG and EDS severity in PD-EDS, suggesting a link between neurodegenerative processes underlying axonal injury and cortical atrophy in key regions associated with EDS in PD. Our findings suggest that combining neuroimaging markers with plasma NfL levels may provide valuable insights into the mechanisms driving EDS progression in PD.
Keywords: cortical thickness, Mediation analysis, Parkinson's disease, neurofilament light chain, excessive daytime sleepiness, functional connectivity, Neuroimaging Biomarkers
Received: 11 Jun 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Chen, Jiang, Zhu, Liang, Liu, Chen, Yang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xinglong Yang, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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