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TRAUMATIC BRAIN INJURY EFFECTS UPON THE STRUCTURAL CONNECTOME MIRROR THOSE CAUSED BY ALZHEIMER’S DISEASE

      Background

      The extent to which mild traumatic brain injury (mTBI) modulates the risk for Alzheimer’s Disease (AD) as a function of age at injury is poorly understood. In many mTBI victims, blood-brain barrier (BBB) disruption is associated with connectome reorganization, leading to neurological deterioration whose severity increases with age. Post-mortem histological examination of brain tissue samples collected from mTBI patients indicates that Amyloid-beta (Aβ) protein deposits are more likely to occur in regions affected by BBB disruption.

      Methods

      We acquired magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) from 20 middle-aged (age: μ∼45.1 years, σ∼7.3 years) and 20 older (age: μ∼68.6 years, σ∼8.4 years) mTBI victims. Data were acquired both within the first few days and 6 months after injury. Multimodal MRI and DTI were combined to generate graph-theoretical representations of network models and to study their spatiotemporal dynamics.

      Results

      Changes in white matter connectivity density [proportion of total tractography streamlines which connect one cortical region to the rest of the brain] are significantly and negatively correlated with the distance between cortex and the closest micro-bleeds (R2: μ=-0.47, SEM=0.21, t39=3.13, p<0.001), both in older (μ=-0.54, SEM=0.29, t39=3.35, p<0.001) and younger patients (μ=-0.41, SEM=0.25, t39=3.41, p<0.001). The rich club coefficients of nodes located in the vicinity of micro-bleeds were found to decrease (R2: μ=0.44, SEM=0.19, t39=3.44, p<0.001). Changes to network topology in the vicinity of micro-bleeds were found to be strongly correlated (R2: μ=0.54, SEM=0.23, t39=3.24, p<0.001) with decreases in Glasgow Outcome Score. Areas found to be associated with brain network deterioration are known to be responsible for memory formation (medial temporal lobe), personality (prefrontal cortex), cognitive control (anterior limbic areas) and language (ventromedial temporal lobe).

      Conclusions

      Damage to regions often affected by AD appears to increase with age, as does the probability that brain network damage and neurological function deterioration due to mTBI is associated with these regions. Since these areas also feature substantial Aβ deposition in both AD and mTBI, this research can help to understand the relationship between AD-like brain changes, deficits prompted by mTBI, and the extent to which mTBI may increase AD risk.