Consequences of brain injuries from blast exposure and other war related injuries are poorly understood. The interplay of TBI and cognitive and affective symptoms in OIF/OEF veterans over time has not been adequately explored. Mild TBI and neuropsychological symptoms may not become evident until after military personnel return home. Evidence-based guidelines for diagnosis and treatment are limited. The current project, conducted in cooperation with the PT/BRI-QUERI and the Polytrauma Research Consortium, began as a clinical initiative in VISN 2. Our goal was to provide evidence-based understanding of cognitive and affective correlates of TBI in OEF/OIF veterans, symptom relationship to health care utilization and quality of life factors, and the evolution of the phenomena over time.
(1) Provide a psychometric study of the VA TBI Screening Tool.
(2) Describe war related cognitive and affective symptoms and patterns of substance abuse in OEF/OIF veterans.
(3) Construct cognitive and affective profiles of OEF/OIF veterans over time.
(4) Describe the temporal relationship between the composite stress index and the cognitive profiles of OEF/OIF veterans.
(5) Describe the temporal relationships among TBI, cognitive symptoms (attention, memory and executive functioning), patient outcomes (quality of life and community participation), and health services outcomes (VA health care utilization), controlling for patient and deployment characteristics.
This four-year prospective cohort study examined 500 OEF/OIF Veterans from six VISN2 sites. Participants completed comprehensive neuropsychological assessments on four occasions: baseline and at 6, 12, and 18 month intervals. Analyses included descriptive and multivariate methods, as well as sensitivity/specificity analyses of the VA TBI clinical reminder. The temporal relationships of TBI status, cognitive symptoms and patient outcomes, controlling for patient and deployment characteristics, were examined in a series of multiple regression analyses.
Objective 1- We found that the VA TBI clinical reminder had high internal consistency, high test-reliability, high sensitivity and moderate specificity. When Veterans with probable PTSD were excluded from analysis, the lower bound estimate of the diagnostic odds ratio for the TBI screening tool was extremely high (24). In the "real world" context, including all Veterans in our sample, the DOR remained impressive, with a lower bound DOR estimate of 12.6, suggesting that Veterans who screened positive for TBI based on this tool were over 12 times more likely to have actually sustained such an injury than were Veterans who screened negative. The presence of significant PTSD symptoms reduced the specificity of the measure and highlighted the need for careful clinical follow-up of positive screens. Nonetheless, we concluded that the VA TBI clinical reminder is a valid and reliable screening tool for Veterans and can inform primary care providers of when to refer for further workup for cases of suspected TBI.
Objective 2- While Veterans with TBI performed worse than those without TBI on several measures of attention, executive functions, and memory, all scores remained grossly within normal limits. Given the substantial mean time since TBI for our participants (approximately 3 1/2 years), it was not surprising that most, if not all, cognitive deficits directly associated with mTBI would be resolved.
In contrast to relatively few cognitive problems, the cohort as a whole reported significant symptoms of PTSD, depression, generalized anxiety and neurobehavioral symptoms. On each of these measures, Veterans with TBI reported symptom rates significantly higher than Veterans without TBI. Mean scores on the AUDIT-C did not distinguish Veterans with and without TBI. Both groups reported alcohol use above the cutoff for misuse. The groups also did not differ with regard to illicit drug use, with all Veterans reporting low levels regardless of TBI status.
Results for Objectives 3-5 are preliminary. Analyses are on-going. Healthcare utilization data are in preparation.
Objective 3- Preliminary analysis of cognitive scores at enrollment revealed that Trail Making Test- A (TMT-A: attention), TMT-B (executive functions), and California Verbal Learning Test-2 (CVLT) long-delayed free recall (memory) had the greatest effect sizes per domain in distinguishing TBI positive and negative subgroups (.26, .26, and .46, respectively). Examination of mean scores for the two groups over time showed progressive improvement for each test. Not surprisingly, the TBI negative group consistently scored better than those with TBI, but all scores for both groups remained within normal limits.
Review of affective symptom reports over time showed that Veterans without TBI endorsed mild depression and generalized anxiety and moderate PTSD across all time points. TBI positive Veterans reported moderate depression and anxiety at times one through three but declined to mild levels at time four. PTSD symptoms, however, remained severe at each assessment for this group.
Objective 4- Generalized estimating equation (GEE) models, using lagged predictor variables (TBI status, PCL, BDI, and BAI scores, and pain ratings), revealed that higher generalized anxiety and pain ratings were related to lower digit span scores, but not to other measures of attention. The other predictors, including TBI status, were non-contributory for the other attention tests. In the memory domain, positive TBI status and higher PCL scores were related to lower scores on three primary CVLT measures: list learning, short-delayed free recall, and long-delayed free recall. Poorer lagged performance on three executive functions measures, TMT-B, DKEFS Color-Word and Verbal Fluency Tests, was associated with higher PCL scores. TBI positive status was related to lower (but normal) memory performance over time and was unrelated to attention and executive function scores.
Objective 5- Life satisfaction (SWLS) was significantly associated with executive functioning (TMT-B) at each time point, after removing variance associated with the Combat Experiences Scale and positive TBI status. The Physical Functioning scale of the SF-36 also showed significant associations with executive functioning, once again controlling for combat experiences and TBI. An even greater association of executive functioning was observed in relation to the SF Mental Health score at each time point, controlling for variance associated with combat experience and TBI. An interesting pattern of effect size and statistical significance was observed in the relationship of TBI to outcomes scores. For example, at time 1, TBI accounted for 13% of mental health variance after removing 12% associated with combat experience. However, the TBI association with mental health was not significant at times 2, 3 and 4. Similarly, TBI accounted for significant proportions of life satisfaction variance at times 1 and 2 (8% and 7%, respectively), but not at times 3 and 4. Plausible explanations of this pattern include an actual decrease in TBI impact on mental health and life satisfaction as well as participant dropout (to be examined in subsequent analyses).
Project Modification: Diffusion Tensor Imaging Substudy- We studied a nested cohort of 52 participants with MRI and DTI to understand the relationship of mild TBI and blast exposure to brain white matter structure, and how these interact to impact the development of PTSD. Multivariate analyses were used to relate these clinical and neuroimaging variables to PTSD and to blast exposure. PTSD severity was related both to the severity of combat stress and underlying structural brain changes on MRI and DTI. A clinical diagnosis of mild TBI did not appear to play a role. The observed relationship between blast exposure and abnormal DTI suggested that subclinical TBI may play a role in the genesis of PTSD in a combat environment.
While TBI was confirmed in almost half our sample, the injuries tended to be mild, temporally remote, and generally unrelated to significant cognitive impairment across four assessment points. By contrast, neurobehavioral complaints (including subjective sense of cognitive impairment) and emotional symptoms were common at all time points, even for Veterans without TBI. Our findings underscore the need to educate Veterans on the nature, course, and prognosis of mTBI and to explain how common comorbid conditions, such as PTSD, depression, generalized anxiety, substance misuse and pain can account for many symptoms typically considered to be related to mTBI. Just as VA has implemented a successful screening protocol for TBI, which we found to be reliable and valid, routine assessment of the comorbid conditions listed above might help to create a more comprehensive clinical profile of our Veterans, which can in turn lead to more tailored and effective treatment planning and better outcomes.
External Links for this Project
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