Prediction of brain age
suggests accelerated atrophy after traumatic brain injury

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

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.

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

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
by: Jeff Driban


Cole JH, Leech R, Sharp DJ, & Alzheimer’s Disease Neuroimaging Initiative (2015). Prediction of brain age suggests accelerated atrophy after traumatic brain injury. Annals of Neurology, 77 (4), 571-81 PMID: 25623048