Prediction of brain age suggests accelerated atrophy after traumatic brain injury
Cole JH., Leech R., Sharp DJ. Ann Neurol. 2015;77:571-581
Take Home Message: A patient with a moderate or severe traumatic brain injury is likely to have structural brain changes that are associated with an older brain than his/her actual age.
Sustaining a traumatic brain injury (TBI) triggers a sequence of physiological events that could cause brain atrophy, neurodegeneration, and accelerate the aging process for the brain. If we can determine the discrepancy between normal aging and pathologic brain aging this could help us predict who is at risk for neurological diseases (e.g., Alzheimer, schizophrenia). This would also help us develop future treatments and better understand the origins of neurological diseases. Therefore, the authors developed a predictive model of brain aging based on magnetic resonance (MR) images and tested whether patients with a history of a TBI had an “older” brain than would be predicted for their age. First, the authors collected MR images from 1,537 healthy participants from 8 publically accessible neuroimaging initiatives and developed a model of how the brain ages as we get older (chronological age). The MR-based structural neuroimaging prediction model determined chronological age within both grey and white matter. The authors then applied this model to MR images from a second healthy cohort (113 participants) and 99 patients with persistent neurological problems following TBI. Based on the Mayo Classification System, 17 patients had a mild TBI and 82 had a moderate/severe TBI at least one month before testing (range 1 to 563 months). In this classification system, a moderate-severe TBI is associated with loss of consciousness for 30 minutes or more and post-traumatic amnesia for more than a day. This second step allowed the authors to confirm whether their model worked in healthy adults and test their theory that patients with a history of TBI will have an “older” brain. The authors calculated the predicted age difference as the difference between the expected brain structure for a person’s age and the actual brain structure. The TBI participants also underwent supervised learning to measure processing speed, executive functioning, memory, and reaction time. TBI patients’ demonstrated higher white and grey matter predicted age difference (4.7 and 6.0 years, respectively) differences compared with controls (0.1 and 2.1 years, respectively). TBI participants classified as moderate or severe TBI had greater predicted age differences but mild cases were similar to the control cohort. More impaired processing speed and memory were associated with greater grey and white matter predicted age differences, and more compromised executive function was correlated to greater grey matter predicted age difference. There was no difference between predictive age difference score and mechanism of injury.
This was the first study to demonstrate that structural brain changes resemble the atrophy seen during aging. Severe and moderate TBI produces a pattern of structural changes that affect the apparent age of both grey and white matter compared with controls. This MR imaging model was valid since it was able to predict the true age of the healthy participants. According to this predictive model a patient who sustains a moderate/severe TBI could develop an “older” looking brain compared with the patient’s actual age. Processing speed and memory impairments have been associated with aging, and the current study suggests that TBI may accelerate this cognitive dysfunction. The authors suggest that this supports the idea that TBI triggers accelerated tissue loss over time and promotes neurodegeneration. However, it is still unclear whether the structural changes were due to neurodegeneration triggered by the TBI or an interaction with normal aging. Future studies employing the predictive aging difference score could give insight for clinical outcome score or become a maker of treatment efficacy. This study can help clinicians talk with their patients about the long-term effects of moderate-severe TBI. We should inform patients that there is some evidence that these severe injuries can accelerate brain aging.
Questions for Discussion: Do you think concussions could accelerate brain aging? Do you think age of injury could affect this apparent acceleration?
Written by: Jane McDevitt, PhD
Reviewed by: Jeff Driban