Objective-To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). Design-Longitudinal cohort study. Setting-Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers.Participants-Subjects enrolled in the TBIMS national dataset. Interventions-Not applicable.Main Outcome Measures-Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended.Results-Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (≥40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. While DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. Additionally, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model demonstrated that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates.Conclusions-This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. Additionally, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.Reprint requests to Ramon Diaz-Arrastia, MD, PhD, 5323 Harry Hines Blvd, Dallas, TX 75390-9036, e-mail: ramon.diazarrastia@utsouthwestern.edu. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. The resulting injuries range from mild disability to longterm disabilities or death. 3 It has been observed that particular subpopulations recover differently from similar injuries. One characteristic felt to have an impact on the degree of recovery is age: in general, the older the patient the worse the outcome. 7-12 Issues of TBI and aging are important to study because of the large and growing number of older people who are affected by TBI, which has a bimodal age distribution peaking in late adolescence/early adulthood and again after age 70. 3 NIH Public AccessTBI may interact negatively with aging in at least 2 ways: (1) recovery after TBI is more limited for older than younger survivors; and (2) older individuals who have suffered a TBI are at higher risk for progressive cognitive decline. First, advanced age at the time of injury may result in less complete recovery comp...

Background: Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem.Objective: To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome.Design: Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. Setting: Inpatient traumatic brain injury unit. Patients: From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age-and sex-matched controls.Main Outcome Measures: Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale-Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients.Results: At least 1 fiber variable of each region showed diffuse axonal injury-associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale-Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. Conclusion:Diffusion tensor tractography-based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.

Objectives: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome. Methods:The participants were 28 patients with mild to severe traumatic axonal injury and 20 age-and sex-matched healthy control subjects. Neuroimaging was obtained 0-9 days postinjury for acute scans and 6-14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used. Results:Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function. Conclusions:Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome. Neurology ® 2011;77:818-826 GLOSSARY AB ϭ angular bundle; AF ϭ arcuate fasciculus; CB ϭ cingulum bundle; CC ϭ corpus callosum; CCab ϭ anterior body of the corpus callosum; CCg ϭ genu of the corpus callosum; CCpb ϭ posterior body of the corpus callosum; CCs ϭ splenium of the corpus callosum; CPF ϭ cerebral peduncular fibers; CPpa ϭ cerebral peduncular fibers to the parietal lobes; CVLT-II ϭ California Verbal Learning Test-II; DCA ϭ discriminant correspondence analysis; DTI ϭ diffusion tensor imaging; FA ϭ fractional anisotropy; FB ϭ fornix body; FC ϭ fornix crus; GCS ϭ Glasgow Coma Scale; IFO ϭ inferior fronto-occipital fasciculus; ILF ϭ inferior longitudinal fasciculus; MD ϭ mean diffusivity; PLS ϭ partial least-squares; ROI ϭ region of interest; TAI ϭ traumatic axonal injury; TBI ϭ traumatic brain injury; UF ϭ uncinate fasciculus.Traumatic axonal injury (TAI) is strongly linked to high mortality and morbidity in traumatic brain injury (TBI).1 TAI is progressive with typical occurrence of cytoskeletal disruption within 4 -6 hours postinjury and disconnection of axons between 1 and 7 days.2 Secondary axotomy, which damages brain structur...

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Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3T magnet. Patients were scanned approximately eight months post-injury, and underwent an outcomes assessment at that time. Histogram analysis of FA and MD showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.

Diffusion tensor imaging (DTI) has been useful in showing compromise after traumatic axonal injury (TAI) at the chronic stage; however, white matter (WM) compromise from acute stage of TAI to chronic stage is not yet well understood. This study aims to examine changes in WM integrity following TAI by obtaining DTI, on average, 1 d post injury and again approximately seven months post-injury. Sixteen patients with complicated mild to severe brain injuries consistent with TAI were recruited in the intensive care unit of a Level I trauma center. Thirteen of these patients were studied longitudinally over the course of the first seven months post-injury. The first scan occurred, on average, 1 d after injury and the second an average of seven months post-injury. Ten healthy individuals, similar to the cohort of patients, were recruited as controls. Whole brain WM and voxel-based analyses of DTI data were conducted. DTI metrics of interest included: fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD). tract-based spatial statistics were used to examine DTI metrics spatially. Acutely, AD and RD increased and RD positively correlated with injury severity. Longitudinal analysis showed reduction in FA and AD ( p < 0.01), but no change in RD. Possible explanations for the microstructural changes observed over time are discussed.

Clinicians and researchers should take race/ethnicity into account when utilizing measures of community integration.