Mild traumatic brain injury: The effect of age at trauma onset on brain structure integrity

Abstract

Mounting evidence suggests that mild traumatic brain injuries (mTBI) have long-term effects that interact with the aging process to precipitate cognitive decline. This line of research predicts that early exposure to brain trauma is particularly detrimental to long-term brain integrity. However, a second line of research into the effects of age at trauma onset predict that older brains are more vulnerable to the effects of mTBI than younger brains. We sought to determine whether patients who sustain a mTBI earlier in life fare better than patients who sustain a mTBI at an older age. We conducted a multi-cohort, case-control study, with participants randomly sampled from a population of patients with a history of mTBI. We recruited two cohorts of aging participants ( N = 74, mean [SD] = 61.16 [6.41]) matched in age and education levels that differed in only one respect: age at mTBI onset. One cohort sustained their concussion in their early twenties (24.60 [6.34] y/o), the other in their early sixties (61.05 [4.90] y/o). Each mTBI cohort had its own matched control group. Participants underwent high-resolution MRI at 3 Tesla for T 1 and diffusion-weighted images (DWI) acquisition. Images were processed and analyzed using Deformation-Based Morphometry and DWI Tract-Based Spatial Statistics to identify group differences in a 2 × 2 ANOVA design. Results showed a significant interaction on DWI measures of white matter integrity indicating larger anomalies in participants who sustained a mTBI at a younger age ( F 1,70 , P < .05, FDR corrected). These findings suggest that mTBI initiates a lifelong neurodegeneration process that outweighs the risks associated with sustaining a mTBI at an older age. Implications are important for young athletes' populations exposed to the risk of mTBI in the practice of their sports and for retired athletes aging with a history of concussions sustained at a younger age.

Systematic Review of the Long-Term Neuroimaging Correlates of Mild Traumatic Brain Injury and Repetitive Head Injuries

“…Studies that examined adults in the general population who were exposed to remote mTBI typically found higher AD, RD, and MD (but not FA) in areas that included the fornix/stria terminalis, anterior corona radiata, superior longitudinal fascilus, cingulum angular bundle, the anterior aspect of the corpus callosum, and frontal white matter ( 35 , 49 , 61 ). These studies demonstrated white matter differences in adults with remote mTBI compared to healthy controls who were either the same age or younger.…”

“…The imaging techniques used in these studies were also diverse. However, there was evidence of different levels of metabolites in several brain regions for athletes compared to controls which may be indicative of neuroinflammation ( 48 , 62 , 66 , 73 ) and white matter disruption in widespread areas ( 49 , 52 , 71 ). As per the above sections, methodological considerations (i.e., distinct study designs and methods for selecting brain regions and quantifying metabolites) limit the conclusions that can be drawn from these data.…”

“…Of these, the majority of the samples were comprised of retired NFL or CFL players ( 32 , 33 , 36 , 44 , 45 , 50 , 51 , 53 , 55 , 56 , 58 , 59 , 72 , 74 , 75 ). The other studies included professional fighters ( 34 , 65 , 67 , 68 ) or athletes from other contact sports ( 48 , 49 , 52 , 62 , 66 , 69 – 71 , 73 ). The neuroimaging research done in former NFL or CFL players has revealed differences compared to control samples in the presence and greater length of cavum septum pellucidum and volumes in the amygdala and hippocampus using structural MRI ( 53 , 55 , 56 , 59 ).…”

“…Other studies examined athletes who played a variety of professional contact sports including rugby ( 52 ), soccer ( 70 , 71 , 73 ), a mix of several sports ( 66 , 69 ) and/or levels of play (e.g., university level and professional) ( 49 ), as well as university-level hockey/football ( 48 , 62 ). The imaging techniques used in these studies were also diverse.…”

Blood–Brain Barrier Degradation and the Implication of SPARC Protein as a Potential Therapeutic Target for Alzheimer’s Disease

“…A meta-analysis of studies conducted from 1995 to 2012 found that TBI and mTBI events are substantial risk factors for AD (36). The BBB disruption at the onset of TBI is relatively short-lived; however, the subsequent events lead to structural degeneration in the brain causing long-lasting cognitive impairments (37). Disruption of the BBB has been observed to be a marker of mild cognitive impairment independently of the neurofibrillary tangles (NFTs), tau protein, and Aβ amyloid plaques, indicating that substantial breakdown of the BBB itself contributes to cognitive decline in addition to exacerbating other neurodegenerative processes in AD (38).…”