Biomarker evidence of neurodegeneration in mid-life former rugby players
Notice bibliographique
Résumé
Repetitive head impacts and traumatic brain injuries in contact sports, such as rugby union, are associated with increased risk of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. Advances in fluid and imaging biomarkers are transforming dementia diagnosis but have not been systematically applied to individuals previously exposed to head impacts during rugby participation. We used biomarkers, including those with sensitivity and specificity for early Alzheimer's pathology to explore neurodegenerative risk in mid-life elite retired rugby players with significant repetitive head impact exposure. Plasma neurofilament light, glial fibrillary acid protein, amyloid-β (Aβ)42, Aβ40 and phospho-tau217 were quantified using ultrasensitive single molecule array digital enzyme-linked immunosorbent assay (SiMoA) in former elite rugby players as well as age/sex-matched unexposed controls. 3 T MRI and neuropsychology assessments were performed, with National Institute for Neurological Disorders and Stroke criteria used to ascertain the presence of traumatic encephalopathy syndrome. Regression models were used to relate plasma/imaging biomarkers to clinical phenotype. Individual-levels analyses were performed for fluid and imaging metrics, based on control biomarker distributions. Biomarker data from two aligned un-exposed Alzheimer's cohorts were included to contextualize our findings. Two hundred ex-rugby players (median age 44 years, 90% males) and 33 unexposed controls were assessed. Twenty-four (12%) ex-players fulfilled criteria for traumatic encephalopathy syndrome but none had dementia. Plasma phospho-tau217 concentrations were 17.6% higher in ex-rugby players than controls (95% confidence interval 3.7-33.3, P = 0.047). A total of 46 (23.1%) ex-players had elevated phospho-tau217 at the individual level; as did 18 (9.0%) players in relation to raised plasma neurofilament light. Ex-players' concentrations were lower than in unexposed adults with late onset Alzheimer's disease (n = 69). Ex-players also showed significantly reduced volumes in the frontal/cingulate cortex on voxel-based morphometry at the group level; with reduced white matter and lower hippocampal volume associated with longer career durations within ex-players. Trauma-associated white matter changes measured with diffusion tensor imaging were uncommon in ex-players (4.6%). Traumatic encephalopathy syndrome was significantly more common in ex-players with elevated phospho-tau217, while those with raised plasma neurofilament light had significantly more anxiety and depressive symptoms. Frontal brain volumes correlated negatively with neurofilament light (r = -0.21, P = 0.010), and hippocampal volumes correlated negatively with phospho-tau217 (r = -0.19, P = 0.024). Elite rugby participation is associated with abnormal fluid and neuroimaging neurodegeneration biomarkers in mid-life. These include elevated phospho-tau217, which may indicate amyloid-dependent tau pathology. The results provide support for using state-of-the-art neurodegenerative biomarkers in the evaluation of long-term effects of sports head impact exposure.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
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| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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