Three approaches to investigating functional compromise to the default mode network after traumatic axonal injury.

The default mode network (DMN) is a reliably elicited functional neural network with potential clinical implications. Its discriminant and prognostic utility following traumatic axonal injury (TAI) have not been previously investigated. The present study used three approaches to analyze DMN functional connectedness, including a whole-brain analysis [A1], network-specific analysis [A2], and between-node (edge) analysis [A3]. The purpose was to identify the utility of each method in distinguishing between healthy and brain-injured individuals, and determine whether observed differences have clinical significance. Resting-state fMRI was acquired from 25 patients with TAI and 17 healthy controls. Patients were scanned 6-11 months post-injury, and functional and neurocognitive outcomes were assessed the same day. Using all three approaches, TAI subjects revealed significantly weaker functional connectivity (FC) than controls, and binary logistic regressions demonstrated all three approaches have discriminant value. Clinical outcomes were not correlated with FC using any approach. Results suggest that compromise to the functional connectedness of the DMN after TAI can be identified using resting-state FC; however, the degree of functional compromise to this network, as measured in this study, may not have clinical implications in chronic TAI.

Clinical phenotype of dementia after traumatic brain injury.

Traumatic brain injury (TBI) in early to mid-life is associated with an increased risk of dementia in late life. It is unclear whether TBI results in acceleration of Alzheimer's disease (AD)-like pathology or has features of another dementing condition, such as chronic traumatic encephalopathy, which is associated with more-prominent mood, behavior, and motor disturbances than AD. Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set was obtained over a 5-year period. Categorical data were analyzed using Fisher's exact test. Continuous parametric data were analyzed using the Student's t-test. Nonparametric data were analyzed using Mann-Whitney's test. Overall, 877 individuals with dementia who had sustained TBI were identified in the NACC database. Only TBI with chronic deficit or dysfunction was associated with increased risk of dementia. Patients with dementia after TBI (n=62) were significantly more likely to experience depression, anxiety, irritability, and motor disorders than patients with probable AD. Autopsy data were available for 20 of the 62 TBI patients. Of the patients with TBI, 62% met National Institute of Aging-Reagan Institute "high likelihood" criteria for AD. We conclude that TBI with chronic deficit or dysfunction is associated with an increased odds ratio for dementia. Clinically, patients with dementia associated with TBI were more likely to have symptoms of depression, agitation, irritability, and motor dysfunction than patients with probable AD. These findings suggest that dementia in individuals with a history of TBI may be distinct from AD.