Accelerated Brain Aging in Mild Traumatic Brain Injury: Longitudinal Pattern Recognition with White Matter Integrity

Abstract

Mild traumatic brain injury (mTBI) initiating long-term effects on white matter integrity resembles brain-aging changes, implying an aging process accelerated by mTBI. This longitudinal study aims to investigate the mTBI-induced acceleration of the brain-aging process by developing a neuroimaging model to predict brain age. The brain-age prediction model was defined using relevance vector regression based on fractional anisotropy from diffusion tensor imaging of 523 healthy individuals. The model was used to estimate the brain-predicted age difference (brain-PAD) between the chronological and estimated brain age in 116 acute mTBI patients and 63 healthy controls. Fifty patients were followed for 6 ∼ 12 months to evaluate the longitudinal changes in brain-PAD. We investigated whether brain-PAD was greater in patients of older age, post-concussion complaints, and apolipoprotein E (APOE) ɛ4 genotype, and whether it had the potential to predict neuropsychological outcomes. The brain-age prediction model predicted brain age accurately (<i>r</i> = 0.96). The brains of mTBI patients in the acute phase were estimated to be "older," with greater brain-PAD (2.59 ± 5.97 years) than the healthy controls (0.12 ± 3.19 years) (<i>p</i> < 0.05), and remained stable 6-12 month post-injury (2.50 ± 4.54 years). Patients who were older or who had post-concussion complaints, rather than APOE ɛ4 genotype, had greater brain-PADs (<i>p</i> < 0.001, <i>p</i> = 0.024). Additionally, brain-PAD in the acute phase predicted information processing speed at the 6 ∼ 12 month follow-up (<i>r</i> = -0.36, <i>p</i> = 0.01). In conclusion, mTBI accelerates the brain-aging process, and brain-PAD may be capable of evaluating aging-associated issues post-injury, such as increased risks of neurodegeneration.