Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI.

BACKGROUND: We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury. METHODS: A total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers. RESULTS: TBI patients showed progressive volume loss regardless of injury severity over several years, and TAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years. DISCUSSSION: Spatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI. HIGHLIGHTS: In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

Cross-Walk Comparison of the DVBIC-TBICoE and LIMBIC-CENC Combat-Related Concussion Prospective Longitudinal Study Datasets.

OBJECTIVE: To describe and compare cohorts between 2 large, longitudinal, federally-funded TBI studies of Service members and veterans across demographic, self-report, and neuropsychological variables. DESIGN: Analysis of data from the DVBIC-TBICoE and LIMBIC-CENC prospective longitudinal studies (PLS). SETTING: Recruitment locations spanning Department of Defense and Veterans Affairs hospitals across the U.S. PARTICIPANTS: 1463 participants (N=1463) enrolled in the DVBIC-TBICoE study and divided among non-injured (NIC) (n=191), injured control (IC) (n=349), mild TBI (mTBI) (n=682), and (severe, moderate, penetrating, and complicated mild traumatic brain injury (smcTBI) (n=241) subgroups. 1550 participants enrolled in the LIMBIC-CENC study and divided between IC (n=285) and mTBI (n=1265) subgroups. IC and mTBI study groups were compared across demographic and military characteristics, self-reported symptoms, and neuropsychological test scores. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Neurobehavioral Symptom Inventory, PTSD Checklist-Military Version, TBI quality of life, Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-IV Visual Puzzles, Symbol Search, Coding, Letter-Number Sequencing, and Digit Span, Trail Making Test, Delis-Kaplan Executive Functioning System Verbal Fluency, Letter Fluency, and Category Fluency, California Verbal Learning Test-II, and Grooved Pegboard. RESULTS: Compared with DVBIC-TBICoE, LIMBIC-CENC participants have higher enrollment age, education level, proportion of Black race, and time from injury as well as less combat deployments and are less likely to be married. The distribution of military service branches also differed. Further, symptom profiles differed between cohorts. LIMBIC-CENC participants endorsed higher posttraumatic stress disorder symptomatology. DVBIC-TBICoE study IC participants endorsed higher somatosensory and vestibular symptoms (medium effect sizes). Other symptom measure differences had very small effect sizes (≤0.2). Differences were found on many cognitive test results, but are difficult to interpret given the demographic differences and generally very small effect sizes. CONCLUSIONS: The heavy use of National Institutes of Health common data elements in both studies and collaboration with the DVBIC-TBICoE study team on development of the LIMBIC-CENC assessment battery enabled this comparative analysis. Results highlight unique differences in study cohorts and add perspective and interpretability for assimilating past and future findings.

Elevated Serum Tau and UCHL-1 Concentrations Within 12 Months of Injury Predict Neurobehavioral Functioning 2 or More Years Following Traumatic Brain Injury: A Longitudinal Study.

OBJECTIVE: Blood-based biomarkers have received considerable attention for their diagnostic and prognostic value in the acute and postacute period following traumatic brain injury (TBI). The purpose of this study was to examine whether blood-based biomarker concentrations within the first 12 months of TBI can predict neurobehavioral outcome in the chronic phase of the recovery trajectory. SETTING: Inpatient and outpatient wards from 3 military medical treatment facilities. PARTICIPANTS: A total of 161 service members and veterans classified into 3 groups: (a) uncomplicated mild TBI (MTBI; n = 37), (b) complicated mild, moderate, severe, penetrating TBI combined (STBI; n = 46), and (c) controls (CTRL; n = 78). DESIGN: Prospective longitudinal. MAIN MEASURES: Participants completed 6 scales from the Traumatic Brain Injury Quality of Life (ie, Anger, Anxiety, Depression, Fatigue, Headaches, and Cognitive Concerns) within 12 months (baseline) and at 2 or more years (follow-up) post-injury. Serum concentrations of tau, neurofilament light, glial fibrillary acidic protein, and UCHL-1 at baseline were measured using SIMOA. RESULTS: Baseline tau was associated with worse anger, anxiety, and depression in the STBI group at follow-up (R2 = 0.101-0.127), and worse anxiety in the MTBI group (R2 = 0.210). Baseline ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) was associated with worse anxiety and depression at follow-up in both the MTBI and STBI groups (R2Δ = 0.143-0.207), and worse cognitive concerns in the MTBI group (R2Δ = 0.223). CONCLUSIONS: A blood-based panel including these biomarkers could be a useful tool for identifying individuals at risk of poor outcome following TBI.

Clinical utility of PTSD, resilience, sleep, and blast as risk factors to predict poor neurobehavioral functioning following traumatic brain injury: A longitudinal study in U.S. military service members.

PURPOSE: This study examined the clinical utility of post-traumatic stress disorder (PTSD), low resilience, poor sleep, and lifetime blast exposure as risk factors for predicting future neurobehavioral outcome following traumatic brain injury (TBI). METHODS: Participants were 591 U.S. military service members and veterans who had sustained a TBI (n = 419) or orthopedic injury without TBI (n = 172). Participants completed the Neurobehavioral Symptom Inventory, PTSD Checklist, and the TBI-Quality of Life (TBI-QOL) scale at baseline and follow-up. RESULTS: Using the four risk factors at baseline, 15 risk factor combinations were examined by calculating odds ratios to predict poor neurobehavioral outcome at follow-up (i.e., number of abnormal scores across five TBI-QOL scales [e.g., Fatigue, Depression]). The vast majority of risk factor combinations resulted in odds ratios that were considered to be clinically meaningful (i.e., ≥ 2.5) for predicting poor outcome. The risk factor combinations with the highest odds ratios included PTSD singularly, or in combination with poor sleep and/or low resilience (odds ratios = 4.3-72.4). However, poor sleep and low resilience were also strong predictors in the absence of PTSD (odds ratios = 3.1-29.8). CONCLUSION: PTSD, poor sleep, and low resilience, singularly or in combination, may be valuable risk factors that can be used clinically for targeted early interventions.

Overground and Virtual Reality Gait Speed Are Associated With Atypical Symptom Reporting in Active Duty Service Members With a History of Mild to Moderate Traumatic Brain Injury.

OBJECTIVE: Physical therapy following traumatic brain injury (TBI) can be negatively impacted by psychological symptoms, atypical symptom reporting, and response bias. We examined rates of Symptom Validity Test (SVT) failure in active duty military service members with a history of mild-moderate TBI and its impact on gait speed. SETTING: Intensive Outpatient Program at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. PARTICIPANTS: Participants were 84 active duty service members with a history of mild-moderate TBI classified as SVT pass ( n = 49) or SVT fail ( n = 35). DESIGN: Retrospective study. MAIN MEASURES: Overground preferred and fast walking speed as well as Computer Assisted Rehabilitation Environment (CAREN) gait speed were recorded. Participants completed the Neurobehavioral Symptom Inventory and the Validity-10 was used to assign patients into the SVT pass and SVT fail groups. Gait speed metrics were compared across these groups and test operating characteristics were calculated. RESULTS: Approximately 42% of the sample was classified into the SVT fail group. All 3 gait speed measures were significantly slower in the SVT fail group than in the SVT pass group ( P s < .001, d s = 0.60-0.80). Gait speed cutoffs for screeners or indicators of atypical reporting were identified. CONCLUSIONS: The potential for response bias is a critical area for the clinician to consider when conducting physical therapy evaluations. Participants in the SVT fail group had slower walking speed on all 3 measures assessed. Several useful cutoffs were identified to serve as screeners or indicators of SVT failure, though these preliminary findings have limitations and need to be replicated.

Is Traumatic Brain Injury Severity in Service Members and Veterans Related to Health-Related Quality of Life in Their Caregivers?

OBJECTIVE: To examine the relationship between service member/veteran (SM/V) traumatic brain injury (TBI) severity with caregiver health-related quality of life (HRQOL). SETTING: Military treatment facility. PARTICIPANTS: Caregivers ( N = 316) of SM/Vs following a TBI divided into 2 groups based on SM/V TBI severity: (1) caregivers of SM/Vs following an uncomplicated mild TBI (UnMTBI Caregiver group, n = 246), and (2) caregivers of SM//Vs following a complicated mild, moderate, severe, or penetrating TBI (STBI Caregiver group, n = 70). The STBI Caregiver group was further divided into 2 subgroups: Parent ( n = 21) versus Intimate Partner ( n = 49). The UnMTBI Caregiver group consisted of intimate partners. DESIGN: Prospective cohort. MAIN MEASURES: Caregivers completed 15 HRQOL measures. RESULTS: Using analysis of variance and chi-square analysis, the UnMTBI Caregiver group reported worse scores on 12 HRQOL measures and more clinically elevated scores for 6 of 15 comparisons than the STBI Caregiver group. The UnMTBI Caregiver group also reported worse scores on 10 HRQOL measures than intimate partners in the STBI Caregiver group and 5 measures than parents in the STBI Caregiver group. Parents reported worse scores on 3 measures than intimate partners in the STBI Caregiver group. The UnMTBI Caregiver group reported more clinically elevated scores for 7 of 15 comparisons than intimate partners in the STBI Caregiver group. CONCLUSION: Intimate partner caregivers of an SM/V following a remote uncomplicated MTBI reported worse HRQOL than intimate partners and parent caregivers of an SM/V following a more severe TBI, mostly likely due to SM/V physical and mental health comorbidities. Interventions that focus on the SM/V's TBI and other comorbidities, the caregiver's behavioral health problems, and the relationship and family factors that interact with each other will likely have the most success in improving individual and family outcomes for military families.

Low resilience following traumatic brain injury is strongly associated with poor neurobehavioral functioning in U.S. military service members and veterans.

OBJECTIVE: The purpose of this study was to examine the relationship between resilience and self-reported neurobehavioral functioning following traumatic brain injury (TBI) in U.S. military service members and veterans (SMVs). A secondary objective was to examine the interaction between resilience and posttraumatic stress disorder (PTSD) on neurobehavioral functioning. METHOD: Participants included 795 SMVs classified into four groups: Uncomplicated Mild TBI (MTBI; n=300); Complicated Mild, Moderate, Severe, or Penetrating TBI (STBI, n 162); Injured Controls (IC, n=185); and Non-injured Controls (NIC, n=148). Two independent cohorts were evaluated - those assessed within 1-year of injury and those assessed 10-years post-injury. SMVs completed self-report measures including the PTSD Checklist-Civilian version, Neurobehavioral Symptom Inventory, and TBI-Quality of Life. RESULTS: Results showed that (1) lower resilience was strongly associated with poorer neurobehavioral functioning across all groups at 1-year and 10-years post-injury, and (2) PTSD and resilience had a robust influence on neurobehavioral functioning at both time periods post-injury, such that SMVs with PTSD and low resilience displayed the poorest neurobehavioral functioning. CONCLUSION: Results suggest that regardless of injury group and time since injury, resilience and PTSD strongly influence neurobehavioral functioning following TBI among SMVs. Future research evaluating interventions designed to enhance resilience in this population is indicated.

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans.

OBJECTIVE: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). METHOD: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. RESULTS: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065-.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052-.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). CONCLUSIONS: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

Apolipoprotein e (APOE) ε4 genotype influences memory performance following remote traumatic brain injury in U.S. military service members and veterans.

The purpose of this study was to examine the association between the apolipoprotein E (APOE) ε4 allele and neurocognitive functioning following traumatic brain injury (TBI) in military service members and veterans (SMVs). Participants included 176 SMVs with a history of remote TBI (≥1 year post-injury), categorized into mild (n = 100), moderate (n = 40), and severe (n = 36) TBI groups. Participants completed a neuropsychological assessment and APOE genotyping (n = 46 ε4+, n = 130 ε4-). Neurocognitive composite scores representing memory, executive functioning, and visual processing speed were computed. ANCOVAs adjusting for race, education, combat exposure, and PTSD symptom severity showed a significant main effect of ε4 on the memory composite, such that ε4+ SMVs exhibited poorer memory performance than ε4- SMVs. When ε2 allele carriers were removed from the analyses, associations with memory were strengthened, demonstrating a possible protective effect of the ε2 allele. No main effect of TBI group was identified on any cognitive composite, nor were there any significant TBI group × Îµ4 status interactions for any cognitive composite. Future studies with larger samples are needed to verify these findings, but our results suggest an important relationship between ε4 status and memory functioning following remote TBI of all severities.

Recent Advances in Blood-Based Biomarkers of Remote Combat-Related Traumatic Brain Injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is highly prevalent among service members and Veterans (SMVs) and associated with changes in blood-based biomarkers. This manuscript reviews candidate biomarkers months/years following military-associated TBI. RECENT FINDINGS: Several blood-based biomarkers have been investigated for diagnostic or prognostic use to inform care years after military-associated TBI. The most promising include increased levels of plasma/serum and exosomal proteins reflecting neuronal, axonal and/or vascular injury, and inflammation, as well as altered microRNA expression and auto-antibodies of central nervous system markers. Diagnostic and prognostic biomarkers of remote TBI outcomes remain in the discovery phase. Current evidence does not yet support single or combination biomarkers for clinical diagnostic use remotely after injury, but there are promising candidates that require validation in larger, longitudinal studies. The use of prognostic biomarkers of future neurodegeneration, however, holds much promise and could improve treatments and/or preventive measures for serious TBI outcomes.

Resilience is associated with health-related quality of life in caregivers of service members and veterans following traumatic brain injury.

PURPOSE: To examine factors related to resilience in military caregivers across caregiver health-related quality of life (HRQOL), caregiver sociodemographic variables, and service member/veteran (SMV) injury and health status. METHODS: Caregivers (N = 346, Female = 96.2%; Spouse = 91.0%; Age: M = 40.6 years, SD = 9.3) of SMVs following a mild, moderate, severe, or penetrating TBI were recruited from U.S. military treatment facilities and via community outreach. Caregivers completed select TBI-CareQOL and NIH Toolbox scales, the Caregiver Appraisal Scale, Caregiver Questionnaire, and Mayo-Portland Adaptability Inventory-4. Caregivers were divided into three groups using the TBI-QOL Resilience scale: (1) Low-Moderate Resilience (n = 125), (2) Moderate Resilience (n = 122), and (3) Moderate-High Resilience (n = 99). RESULTS: Factors related to low caregiver resilience were strain on employment, financial burden from out-of-pocket expenses, caring for children, less personal time, caring for both verbal and physical irritability, anger, and aggression, and lower SMV functional ability (all p's < .05). The Low-Moderate Resilience group had consistently worse HRQOL scores compared to the Moderate and Moderate-High Resilience groups (ps < .001; d = .50-1.60), with the exception of Caregiving Ideology. CONCLUSION: Lower resilience among caregivers of SMVs following TBI is associated with poorer caregiver HRQOL. Programs aimed at promoting and maintaining resilience in military caregivers long-term is important for their own health, the health of the SMV, and the health of their children.

Posttraumatic Stress Disorder is a Stronger Predictor of Long-Term Neurobehavioral Outcomes Than Traumatic Brain Injury Severity.

Concurrent posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) is common in military populations. The purpose of this study was to examine long-term neurobehavioral outcomes in service members and veterans (SMVs) with versus without PTSD symptoms following TBI of all severities. Participants were 536 SMVs prospectively enrolled from three military medical treatment facilities who were recruited into three experimental groups: TBI, injured controls (IC), and noninjured controls (NIC). Participants completed the PTSD Checklist, Neurobehavioral Symptom Inventory, and the TBI-Quality of Life (TBI-QOL) and were divided into six subgroups based on the three experimental categories, two PTSD categories (i.e., present vs. absent), and two broad TBI severity categories (unMTBI, which included uncomplicated mild TBI; and smcTBI, which included severe TBI, moderate TBI, and complicated mild TBI): (a) NIC/PTSD-absent, (b) IC/PTSD-absent, (c) unMTBI/PTSD-absent, (d) unMTBI/PTSD-present, (e) smcTBI/PTSD-absent, and (f) smcTBI/PTSD-present. There were significant main effects across the six groups for all TBI-QOL measures, ps < .001. Select pairwise comparisons revealed significantly lower scores, p < .001, on all TBI-QOL measures in the PTSD-present groups when compared to the PTSD-absent groups within the same TBI severity classification, ds = 0.90-2.11. In contrast, when controlling for PTSD, there were no significant differences among the TBI severity groups for any TBI-QOL measures. These results provide support for the strong influence of PTSD but not TBI severity on neurobehavioral outcomes following TBI. Concurrent PTSD and TBI of all severities should be considered a risk factor for poor long-term neurobehavioral outcomes that require ongoing monitoring.

Long-term neurobehavioural symptom reporting following mild, moderate, severe, and penetrating traumatic brain injury in U.S. military service members.

The purpose of this study was to examine long-term neurobehavioural symptom reporting following mild, moderate, severe, or penetrating TBI in U.S. military service members and veterans (SMV). Participants were 445 SMVs divided into four groups: 158 uncomplicated mild TBI ("unMTBI" group), 105 penetrating, severe, moderate, or complicated mild TBI ("smcTBI" group), 101 injured controls (IC), and 81 non-injured controls (NIC). Two independent cohorts were examined that included participants 5-years or 10-year post-injury. Participants completed the TBI-Quality of Life, Neurobehavioural Symptom Inventory, and Post-traumatic Stress Disorder Checklist. At 5-years and 10-years post-injury, there were significant main effects for the majority of measures (all p's < .005). At 10-years post-injury, the NIC group had consistently better scores compared to the IC, unMTBI, and smcTBI groups. At 5-years post-injury, either (a) the IC and NIC group had better scores compared to both TBI groups, or (b) the NIC group had better scores compared to the IC, unMTBI, and smcTBI groups. A high proportion of SMVs reported poor long-term neurobehavioural symptoms following TBI or bodily injury without TBI. Injured SMVs (regardless of injury type) can have long-term symptoms that impact mental health and overall quality of life requiring long-term follow-up and care.

Caring for a service member or Veteran following traumatic brain injury influences caregiver mental health.

This study examined factors related to poor mental health in caregivers assisting service members and Veterans (SMV) following traumatic brain injury (TBI). Participants were 201 military caregivers (96.0% female; Age: M = 39.2 years, SD = 10.2) of SMVs following a mild, moderate, severe, or penetrating TBI. The SF-36v2 Health Survey, Caregiver Appraisal Scale, Mayo-Portland Adaptability Inventory-4, and Caregiver Questionnaire were completed. Caregivers were divided into two mental health groups: Poor Mental Health (n = 108) and Good Mental Health (n = 93). Factors related to poor caregiver mental health were worse general health and stress appraisal, less personal time, unmet needs, and greater financial and employment strain. Factors also related to poor caregiver mental health included assisting a SMV who had sustained a mild TBI, did not have significant hospital care, had post-traumatic stress disorder, depression, and/or anxiety, was experiencing greater functional disability, and was experiencing physical expressions of irritability, anger, and aggression (all p's<.05; d =.29 to d =.64; OR = 1.911 to OR = 4.984). For many military caregivers, poor mental health may be related to the SMVs ongoing comorbid mental health symptoms and less so neurological impairment related to the brain injury. TBI treatment programs require a holistic approach that addresses the behavioral health concerns of both SMVs and their caregivers.

Concurrent Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Is Associated With Elevated Tau Concentrations in Peripheral Blood Plasma.

Concurrent mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common in U.S. military service members and veterans. Tau and amyloid-beta-42 (Aß42) are proteins that have been linked to cognitive impairment, neurological hallmarks of Alzheimer's disease, and may also relate to recovery from mTBI. However, the role of these proteins in the maintenance or resolution of chronic symptoms has not yet been determined. Participants in the current study were 102 service members and veterans who had sustained an mTBI (n = 84) or injured controls (IC) without TBI (n = 18). They were categorized into three groups based on the presence or absence of mTBI and PTSD: IC/PTSD-Absent (n = 18), mTBI/PTSD-Absent (n = 63), and mTBI/PTSD-Present (n = 21). Concentrations of tau and Aß42 in peripheral blood plasma were measured using SimoaTM , an ultrasensitive technology, and compared across groups. Tau concentrations were highest in the mTBI/PTSD-Present group, F(2, 99) = 4.33, p = .016, compared to the other two groups. Linear multiple regression was conducted to determine the independent effects of PTSD and mTBI on tau concentrations, controlling for gender and sleep medication. PTSD was a significant and independent predictor of tau concentrations, ß = .25, p = .009, ηp 2 = .26. Aß42 concentrations did not differ between the groups. The results indicated that PTSD was associated with an elevation of tau in peripheral blood and suggest that there may be increased biological effects of PTSD in this young cohort of service members and veterans following mTBI.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) La Lesión Cerebral Traumática Leve Concurrente con Trastorno de Estrés Postraumático se asocia a elevadas concentraciones de Tau en Plasma de Sangre Periférica TRASTORNO DE ESTRÉS POSTRAUMÁTICO Y TAU ELEVADA La comorbilidad entre lesión cerebral traumática leve (mTBI por su sigla en inglés) y Trastorno de Estrés Postraumático (TEPT) es común en miembros del ejército estadounidense en servicio y en veteranos. Tau y beta-amiloide-42 (Aß42) son proteínas que han sido relacionadas a deterioro cognitivo, son marcadores neurológicos de Enfermedad de Alzheimer, y pueden también relacionarse a la recuperación de mTBI. Sin embargo, el rol de estas proteínas en la mantención o resolución de síntomas crónicos aún no ha sido determinado. Los participantes del presente estudio fueron 102 miembros en servicio y veteranos que habían sufrido una mTBI (n = 84) o controles heridos (CH) sin TBI (n = 18). Fueron categorizados en tres grupos de acuerdo con la presencia o ausencia de mTBI y TEPT; CH/TEPT-Ausente (n = 18), mTBI/TEPT-Ausente (n = 63) y mTBI-TEPT Presente (n = 21). Se midieron las concentraciones de Tau y Aß42 en plasma de sangre periférica usando SimoaTM , una tecnología ultrasensible, y fueron comparadas entre grupos. Las concentraciones de Tau fueron más altas en el grupo mTBI/TEPT-Presente, F(2, 99) = 4.33, p = .016, en comparación a los otros dos grupos. Se realizó una regresión lineal múltiple para determinar los efectos independientes del TEPT y mTBI sobre la concentración de Tau, controlando el género y la medicación para dormir. El TEPT fue un predictor significativo e independiente de concentraciones de Tau, ß = .25, p = .009, ηp 2 = .26. Las concentraciones de Aß42 no difirieron entre los grupos. Los resultados indicaron que el TEPT se asoció a una elevación de Tau en sangre periférica y sugieren que puede haber efectos biológicos del TEPT incrementados en esta joven cohorte de miembros en servicio y veteranos luego de una mTBI.

Characteristics and Health Outcomes of Post-9/11 Caregivers of US Service Members and Veterans Following Traumatic Brain Injury.

OBJECTIVES: To (a) characterize a sample of post-9/11 caregivers providing help to service members and veterans (SMV) following traumatic brain injury (TBI), (b) examine the level of support provided, and (c) determine caregiver health and well-being outcomes. SETTING: Military treatment facility. PARTICIPANTS: Caregivers (N = 278) of SMVs who sustained a mild, moderate, severe, or penetrating TBI (96.0% female; 86.0% spouse/partner; age: M = 38.7 years, SD = 10.4). Participants were divided into 3 groups on the basis of the level of support provided (low, medium, high). DESIGN: Prospective observational. MAIN MEASURES: Caregiver Appraisal Scale, SF-36v2 Health Survey, Mayo-Portland Adaptability Inventory-4, Caregiver Questionnaire. RESULTS: The majority of caregivers were helping an SMV with mild TBI and comorbid posttraumatic stress disorder/depression, who was injured in a blast-related incident during combat. Caregivers helped predominantly with activities of daily living and/or instrumental activities of daily living and spent more than 40 hours per week providing care. High-support caregivers were more likely to be caring for an SMV with comorbid posttraumatic stress disorder, report poor physical and mental health outcomes, and have a negative impact on employment and finances. CONCLUSIONS: A better understanding of protective factors is required to ensure that burden of care does not exceed the caregiver's health and financial capacity, or undermine the care, well-being, and recovery of the SMV.

Postconcussion Symptom Reporting After Mild Traumatic Brain Injury in Female Service Members: Impact of Gender, Posttraumatic Stress Disorder, Severity of Injury, and Associated Bodily Injuries.

OBJECTIVE: Examine effects of diagnostically relevant posttraumatic stress disorder (PTSD) symptoms, mild traumatic brain injury (TBI) severity, and associated bodily injury severity on postconcussion symptom reporting in female service members (SM) compared with a matched sample of male SM. SETTING: Six US military medical treatment facilities. PARTICIPANTS: A total of 158 SM (79 females, 79 males) evaluated within 30 months after mild TBI. Men and women were matched by age, days postinjury, PTSD symptom status, mild TBI severity, and bodily injury severity. All passed a measure of symptom validity. DESIGN: Compare reported postconcussion symptoms for men and women stratified by PTSD diagnostic symptoms (present/absent), mild TBI severity (alteration of consciousness/loss of consciousness), and bodily injury severity (mild/moderate-severe). MAIN MEASURES: Neurobehavioral Symptom Inventory, PTSD Checklist, Abbreviated Injury Scale. RESULTS: Overall postconcussion symptom reporting increased with PTSD but did not significantly differ based on severity of mild TBI or associated bodily injury. Females reported more somatosensory and/or vestibular symptoms than males under some circumstances. Females in the PTSD-Present group, Alteration of Consciousness Only group, and Moderate-Severe Bodily Injury group reported more somatosensory symptoms than males in those groups. Females in the Alteration of Consciousness Only group and Minor Bodily Injury group reported more vestibular symptoms than males in those groups. CONCLUSION: Diagnostically relevant PTSD symptoms, mild TBI severity, and bodily injury severity differentially impact somatosensory and vestibular postconcussion symptom reporting for male and female SM after mild TBI. Controlling for PTSD and symptom validity resulted in fewer gender-based differences in postconcussive symptoms than previously demonstrated in the literature.

Burden among caregivers of service members and veterans following traumatic brain injury.

OBJECTIVES: To determine the (a) health status and caregiving appraisal and (b) influence of perceived burden on health and appraisal in a sample of caregivers helping service member/veterans (SMVs) following a traumatic brain injury (TBI). METHODS: Participants were caregivers (N = 283, female = 96.1%, 86.2% = spouse/partner) of SMVs who sustained a mild-severe or penetrating TBI. Participants completed the Caregiver Appraisal Scale (CAS) and the SF-36v2 Health Survey (SF-36v2). Participants were divided into three burden groups: high, neutral, and low. RESULTS: Almost half the sample (48.8%) reported negative feelings on the CAS Perceived Burden scale. A substantial proportion had lower scores than a normative sample on four SF-36v2 physical health scales (35.1-64.5%) and four mental health scales (70.7-79.8%). A significant main effect was found across caregiver burden groups on three CAS scales (p = 0.010 to p < 0.001), two SF-36v2 component scores (all ps < 0.001), and eight SF-36v2 scales (p = 0.001 to p < 0.001). Caregivers with high perceived burden reported significantly worse scores, except CAS Caregiving Ideology. All CAS and SF-36v2 scales were significant predictors of CAS Perceived Burden scores (all ps< 0.001), with the SF-36v2 Social Functioning scale accounting for the most variance (32.6%). CONCLUSIONS: Health care and social services are needed for caregivers who help SMVs to foster resilience, wellness, and growth.