The consequences of traumatic brain injury (TBI) are sizable in both human and economic terms. In the USA alone, about 1.7 million new injuries happen annually, making TBI the leading cause of death and disability in people younger than 35 years of age. Survivors usually exhibit lifelong disabilities involving both motor and cognitive domains, leading to an estimated annual cost of $76.5 billion in direct medical services and loss of productivity in the USA. This issue has received even more intense scrutiny in the popular media with respect to sports-related concussions where there is a proposed link between having suffered multiple injuries, regardless of severity, with later neurodegeneration. At present, there is a dearth of evidence to either support or undermine the role of sports concussions in the later development of neurodegenerative processes, much less the influence of those brain injuries on the normal aging process.
As most people agree that no two concussions are alike, they all share at least one feature in common; they all involve the near instant transfer of kinetic energy to the brain. The brain absorbs kinetic energy as a result of acceleration forces, while deceleration forces cause it to release kinetic energy when colliding with the skull. Coup contrecoup injury is one of the most ancient and best supported biomechanical models of traumatic brain injury induction. Acceleration/deceleration forces can either be transferred to the brain in a straight line passing through the head’s centre of gravity or in a tangential line and arc around its centre of gravity. Shearing and stretching of axons are common manifestations of inertial forces applied to the brain and this type of damage is commonly referred to as traumatic axonal injury. Although robustly demonstrated in both animal and post-mortem models of TBI, neuroimaging techniques limitations, however, have long prevented us from accurately tracking projecting axonal assemblies, also called white matter fibers, in living humans. The recent emergence of a magnetic resonance imaging (MRI)-based tool called Diffusion Tensor Imaging (DTI) can reveal abnormalities in white matter fibers with increasing sensitivity. DTI has quickly gained in popularity among TBI researchers who have long sought to characterize the neurofunctional repercussions of traumatic axonal injury in living humans. One particularly appealing clinical application of DTI is with athletes who have sustained sports concussion in whom conventional MRI assessments typically turn out negative despite the persistence of long-lasting, cumulative neurofunctional symptoms. First applied to young concussed athletes, a follow-up DTI study conducted in our laboratory revealed subtle white matter tracts anomalies detected in the first few days after the injury and again 6 months later. Interestingly, these young concussed athletes were all asymptomatic at follow-up and performance on concussion-sensitive neuropsychological tests had returned to normal.
In parallel, our group became increasingly interested in the characterization of the remote neurofunctional repercussions of concussion sustained decades earlier in late adulthood former elite athletes. Quantifiable cognitive (i.e. memory and attention) and motor function alterations were found on age-sensitive clinical tests, a finding that significantly contrasts with the full recovery typically found within a few days post-concussion in young, active athletes on equivalent neurofunctional measures. This finding was the first of many demonstrations that a remote history of sports concussion synergistically interacts with advancing age to precipitate brain function decline. These neuropsychological tests performance alterations specific to former concussed athletes were soon after found to correlate significantly with markers of structural damage restricted to ventricular enlargement and age-dependent cortical thinning. However, besides the significant interaction of age and a prior history of concussion on cortical thinning, former concussed athletes could not be differentiated from age-matched unconcussed teammates using highly sophisticated measures of grey matter morphometry. White matter integrity disruptions therefore appeared as a likely candidate to explain the observed significant ventricular enlargement found in former concussed athletes. We thus turned to state-of-the-art DTI metrics to conduct the first study of white matter integrity with older but clinically normal retired athletes with a history of sports-related concussions. A particular emphasis was put on bringing together former elite athletes who were free from confounding factors such as clinical comorbidities, drug/alcohol abuse, and genetic predisposition that are too often confusing the long-term effects of concussions on brain health. Our results show that aging with a history of prior sports-related concussions induces a diffuse pattern of white matter anomalies affecting many major inter-hemispheric, intra-hemispheric as well as projection fiber tracts. Of crucial clinical significance with relation to our previous findings on former concussed athletes, we found ventricular enlargement to correlate significantly with widespread alterations of key markers of white matter integrity including not only peri-ventricular white matter tracts, but also an extensive network of fronto-parietal connections. Most of all, these white matter integrity losses were found to be associated with altered neurocognitive functions including memory and learning.
Taken together with previous functional and structural characterizations of the remote effects of concussion in otherwise healthy older former athletes, the pattern of white matter alterations, being more pronounced over fronto-parietal brain areas, more closely resemble what has been observed in normal aging. From this interpretation, we suggest that concussion induces a latent microstructural injury that synergistically interacts with the aging process to exert late-life brain decline in both structure and function.