Related Experiment Video
Updated: Jul 19, 2025
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Published on: February 7, 2025
Increased brain age and relationships with blood-based biomarkers following concussion in younger populations
Andrew R Mayer1,2,3, Timothy B Meier4,5,6, Josef M Ling7
1The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, 1101 Yale Blvd. NE, Albuquerque, NM, 87106, USA. amayer@mrn.org.
Insights
Brain age is elevated in acute and sub-acute concussion, with recovery differing by age. Repetitive head impacts may increase brain age, but this requires further study.
Area of Science:
- Neuroscience
- Neurology
- Biomarkers
Background:
- Brain age is a neuroimaging biomarker used to assess neuropathological changes.
- Limited data exists on brain age in the acute/sub-acute stages of concussion, particularly in pediatric populations.
Purpose of the Study:
- To investigate brain age differences in pediatric and collegiate athletes following concussion.
- To examine the effects of repetitive head injury on brain age.
Main Methods:
- Predicted brain age differences were calculated in pediatric concussion (N=446) and collegiate athlete (N=184) cohorts.
- Repetitive head injury effects were assessed in contact sport athletes (N=82) using concussion history and participation duration.
Main Results:
- Increased brain age was observed in acute/sub-acute concussion, with faster recovery in pediatric cases.
- Contact sport athletes showed increased brain age, but this was not linked to concussion history.
- Pro-inflammatory markers were elevated, while anti-inflammatory markers correlated inversely with brain age.
Conclusions:
- Chronicity of brain age differences may depend on age at injury, with adults showing longer-lasting effects than children.
- Exposure to contact sports may contribute to increased brain age.
Objective:
Brain age is increasingly being applied to the spectrum of brain injury to define neuropathological changes in conjunction with blood-based biomarkers. However, data from the acute/sub-acute stages of concussion are lacking, especially among younger cohorts.
Methods:
Predicted brain age differences were independently calculated in large, prospectively recruited cohorts of pediatric concussion and matched healthy controls (total N = 446), as well as collegiate athletes with sport-related concussion and matched non-contact sport controls (total N = 184). Effects of repetitive head injury (i.e., exposure) were examined in a separate cohort of contact sport athletes (N = 82), as well as by quantifying concussion history through semi-structured interviews and years of contact sport participation.
Results:
Findings of increased brain age during acute and sub-acute concussion were independently replicated across both cohorts, with stronger evidence of recovery for pediatric (4 months) relative to concussed athletes (6 months). Mixed evidence existed for effects of repetitive head injury, as brain age was increased in contact sport athletes, but was not associated with concussion history or years of contact sport exposure. There was no difference in brain age between concussed and contact sport athletes. Total tau decreased immediately (~ 1.5 days) post-concussion relative to the non-contact group, whereas pro-inflammatory markers were increased in both concussed and contact sport athletes. Anti-inflammatory markers were inversely related to brain age, whereas markers of axonal injury (neurofilament light) exhibited a trend positive association.
Conclusion:
Current and previous findings collectively suggest that the chronicity of brain age differences may be mediated by age at injury (adults > children), with preliminary findings suggesting that exposure to contact sports may also increase brain age.
