Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions

J Neurol. 2024 Jul;271(7):4180-4190. doi: 10.1007/s00415-024-12340-1. Epub 2024 Apr 8.

Abstract

Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.

Keywords: Atrophy; Biomarkers; Concussion; Functional connectivity; Neurodegeneration.

MeSH terms

  • Adult
  • Athletes*
  • Athletic Injuries* / complications
  • Athletic Injuries* / diagnostic imaging
  • Athletic Injuries* / physiopathology
  • Biomarkers* / blood
  • Brain Concussion* / blood
  • Brain Concussion* / diagnostic imaging
  • Brain Concussion* / physiopathology
  • Connectome
  • Default Mode Network / diagnostic imaging
  • Default Mode Network / physiopathology
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology
  • Neurodegenerative Diseases / blood
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / physiopathology
  • Neurofilament Proteins / blood
  • Neuropsychological Tests
  • Young Adult

Substances

  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L