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

Area of Science:

• Neuroimaging
• Traumatic Brain Injury Research
• Aging and Neuroscience

Background:

• Mild traumatic brain injury (mTBI) can lead to long-term white matter changes resembling accelerated brain aging.
• Understanding mTBI's impact on brain aging is crucial for predicting long-term neurological outcomes.
• Existing research highlights the need for reliable biomarkers to assess mTBI-related brain changes.

Purpose of the Study:

• To investigate mTBI-induced acceleration of brain aging using a neuroimaging-based brain age prediction model.
• To quantify the brain-predicted age difference (brain-PAD) in mTBI patients compared to healthy controls.
• To explore the relationship between brain-PAD, clinical factors, and neuropsychological outcomes post-mTBI.

Main Methods:

• Developed a brain-age prediction model using relevance vector regression on fractional anisotropy (FA) from diffusion tensor imaging (DTI) in 523 healthy individuals.
• Applied the model to estimate brain-PAD in 116 acute mTBI patients and 63 healthy controls.
• Conducted longitudinal follow-up for 50 mTBI patients over 6–12 months to assess brain-PAD stability and predictive potential for neuropsychological outcomes.

Main Results:

• The brain-age prediction model demonstrated high accuracy (r = 0.96).
• mTBI patients exhibited significantly greater brain-PAD (2.59 ± 5.97 years) in the acute phase compared to controls (0.12 ± 3.19 years), with values remaining stable at follow-up.
• Older age and post-concussion complaints, but not APOE ɛ4 genotype, were associated with increased brain-PAD. Acute brain-PAD predicted information processing speed at follow-up (r = -0.36).

Conclusions:

• Mild traumatic brain injury accelerates the brain-aging process.
• Brain-PAD serves as a potential imaging biomarker for assessing aging-associated neurological issues and neurodegeneration risks following mTBI.
• The findings support the use of brain-PAD in evaluating long-term consequences of mTBI.