Low resilience is associated with worse health-related quality of life in caregivers of service members and veterans with traumatic brain injury: a longitudinal study.

PURPOSE: To examine [a] the association of caregiver health-related quality of life (HRQOL) and service member/veteran (SMV) neurobehavioral outcomes with caregiver resilience; [b] longitudinal change in resilience at the group and individual level; and [c] the magnitude of change at the individual level. METHODS: Caregivers (N = 232) of SMVs with traumatic brain injury completed a resilience measure, and 18 caregiver HRQOL and SMV neurobehavioral outcome measures at a baseline evaluation and follow-up evaluation three years later. Caregivers were divided into two resilience groups at baseline and follow-up: [1] Low Resilience (≤ 45 T, baseline n = 99, follow-up n = 93) and [2] High Resilience (> 45 T, baseline n = 133, follow-up n = 139). RESULTS: At baseline and follow-up, significant effects were found between Low and High Resilience groups for the majority of outcome measures. There were no significant differences in resilience from baseline to follow-up at the group-mean level. At the individual level, caregivers were classified into four longitudinal resilience groups: [1] Persistently Low Resilience (Baseline + Follow-up = Low Resilience, n = 60), [2] Reduced Resilience (Baseline = High Resilience + Follow-up = Low Resilience, n = 33), [3] Improved Resilience (Baseline = Low Resilience + Follow-up = High Resilience, n = 39), and [4] Persistently High Resilience (Baseline + Follow-up = High Resilience, n = 100). From baseline to follow-up, approximately a third of the Reduced and Improved Resilience groups reported a meaningful change in resilience (≥ 10 T). Nearly all of the Persistently High and Persistently Low Resilience groups did not report meaningful change in resilience (< 10 T). CONCLUSION: Resilience was not a fixed state for all caregivers. Early intervention may stall the negative caregiving stress-health trajectory and improve caregiver resilience.

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.

Health outcomes before and during the COVID-19 pandemic in caregivers of service members and veterans with traumatic brain injury.

PURPOSE: To examine change in health-related quality of life (HRQOL) during the COVID-19 pandemic in caregivers of service members/veterans (SMVs) with traumatic brain injury (TBI), by comparing HRQOL during the first year of the pandemic to HRQOL 12 months pre-pandemic. METHODS: Caregivers (N = 246) were classified into three COVID-19 Pandemic Impact groups based on impact ratings of the pandemic on HRQOL: No Impact (n = 50), Mild Impact (n = 117), and Moderate-Severe Impact (n = 79). Caregivers completed 19 measures across physical, social, caregiving, and economic HRQOL domains, and a measure of SMV Adjustment. T-scores were used to determine individual symptom trajectories for each measure as follows: Asymptomatic (pre + during < 60 T); Developed (pre < 60 + during ≥ 60 T); Improved (pre ≥ 60 T + during < 60 T); and Persistent (pre + during ≥ 60 T). RESULTS: Using ANOVA, during the pandemic, the Moderate-Severe Impact group reported worse scores on 19 measures (d = 0.41-0.89) compared to the No Impact group and 18 measures (d = 0.31-0.62) compared to the Mild Impact group (d = 0.31-0.38). The Mild Impact group reported worse scores on two measures compared to the No Impact group (d = 0.42-0.43). Using the entire sample, the majority of HRQOL measures were classified as Asymptomatic (47.2-94.7%), followed by Persistent (2.4-27.2%). Few were classified as Developed (0.4-12.6%) or Improved (2.4-13.8%). Using repeated measures ANOVA, no meaningful effects sizes were found for mean scores on all measures completed pre-pandemic compared to during the pandemic (d ≤ 0.17). CONCLUSION: The vast majority of caregivers reported stability in HRQOL pre-pandemic compared to during the pandemic. The COVID-19 pandemic was not associated with a high prevalence of decline in caregiver HRQOL.

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.

Changes in Outpatient Healthcare Utilization and Costs Following Mild Traumatic Brain Injury Among Service Members in the Military Health System by Preexisting Behavioral Health Condition Status.

OBJECTIVE: To evaluate changes in healthcare utilization and cost following an index mild traumatic brain injury (mTBI) diagnosis among service members (SMs). We hypothesized that differences in utilization and cost will be observed by preexisting behavioral health (BH) diagnosis status. SETTING: Direct care outpatient healthcare facilities within the Military Health System. PARTICIPANTS: A total of 21 984 active-duty SMs diagnosed with an index mTBI diagnosis between 2017 and 2018. DESIGN: This retrospective study analyzed changes in healthcare utilization and cost in military treatment facilities among SMs with an index mTBI diagnosis. Encounter records 1 year before and after mTBI were assessed; preexisting BH conditions were identified in the year before mTBI. MAIN MEASURES: Ordinary least squares regressions evaluated difference in the average change of total outpatient encounters and costs among SMs with and with no preexisting BH conditions (eg, posttraumatic stress disorder, adjustment disorder). Additional regressions explored changes in utilization and cost within clinic types (eg, mental health, physical rehabilitation). RESULTS: There was a 39.5% increase in overall healthcare utilization during the following year, representing a 34.8% increase in total expenditures. Those with preexisting BH conditions exhibited smaller changes in overall utilization (ß, -4.9; [95% confidence interval (CI), -6.1 to -3.8]) and cost (ß, $-1873; [95% CI, $-2722 to $-1024]), compared with those with no BH condition. The greatest differences were observed in primary care clinics, in which those with prior BH conditions exhibited an average decreased change of 3.2 encounters (95% CI, -3.5 to -3) and reduced cost of $544 (95% CI, $-599 to $-490) compared with those with no prior BH conditions. CONCLUSION: Despite being higher utilizers of healthcare services both pre- and post-mTBI diagnosis, those with preexisting BH conditions exhibited smaller changes in overall cost and utilization. This highlights the importance of considering prior utilization and cost when evaluating the impact of mTBI and other injury events on the Military Health System.

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.

Risk factors for the presence and persistence of posttraumatic stress symptoms following traumatic brain injury in U.S. service members and veterans.

This study aimed to identify risk factors predictive of the presence and persistence of posttraumatic stress disorder (PTSD) symptom reporting following traumatic brain injury (TBI). Participants were 1,301 U.S. service members and veterans (SMVs) divided into four groups: uncomplicated mild TBI (mTBI; n = 543); complicated mild, moderate, severe, and penetrating TBI (n = 230); injured controls (n = 340); and noninjured controls (n = 188). We examined 25 factors related to demographic, injury-related, military-specific, treatment/health care need, and mental health/social support variables. Seven factors were statistically associated with the presence of DSM-IV-TR symptom criteria for PTSD: premorbid IQ, combat exposure, depression, social participation, history of mTBI, need for managing mood and stress, and need for improving memory and attention, p < .001 (51.3% variance). When comparing the prevalence of these risk factors in a longitudinal cohort (n = 742) across four PTSD trajectory groups (i.e., asymptomatic, improved, developed, persistent), a higher proportion of participants in the persistent PTSD group reported worse depression, a lack of social participation, and history of mTBI. Additionally, a higher proportion of participants in the persistent and developed PTSD groups reported the need for managing mood/stress and improving memory/attention. When considered simultaneously, the presence of ≥ 1 or ≥ 2 risk factors was associated with a higher proportion of participants in the developed and persistent PTSD groups, ps < .001. These risk factors may be useful in identifying SMVs at risk for the development and/or persistence of PTSD symptoms who may need intervention.

A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury.

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.

Pain interference and health-related quality of life in caregivers of service members and veterans with traumatic brain injury and mental health comorbidity.

PURPOSE: To examine (1) the relationship between caregiver pain interference with caregiver health-related quality of life (HRQOL), caregiver age, and service member/veteran (SMV) functional ability, and (2) change in caregiver pain interference longitudinally over 5 years. METHOD: Participants were 347 caregivers of SMVs diagnosed with traumatic brain injury (TBI). Caregivers completed the SF-12v2 Health Survey Bodily Pain scale at an initial baseline evaluation and up to four annual follow-up evaluations. Caregivers were divided into three pain interference groups: High Pain Interference (n = 104), Neutral Pain Interference (n = 117), and Low Pain Interference (n = 126). Caregivers also completed 15 HRQOL measures and a measure of SMV functional ability. RESULTS: The High Pain Interference group reported more clinically elevated scores on 13 measures compared to the Low Pain Interference group, and seven measures compared to the Neutral Pain Interference group. The Neutral Pain Interference group had more clinically elevated scores on three measures compared to the Low Pain Interference group. The High and Neutral Pain Interference groups were older than the Low Pain Interference group. Parent caregivers were older than intimate partner/sibling caregivers, but did not report worse pain interference. Caregiver age, and measures of Fatigue, Strain, Perceived Rejection, and Economic QOL were the strongest predictors of pain interference (p < .001), accounting for 28.2% of the variance. There was minimal change in Bodily Pain scores over five years. The interaction of time and age was not significant (X2 = 2.7, p = .61). CONCLUSION: It is important to examine pain in the context of HRQOL in caregivers, regardless of age.

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.

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.

Relationship satisfaction among spouse caregivers of service members and veterans with comorbid mild traumatic brain injury and post-traumatic stress disorder.

This study examined relationship satisfaction and health-related quality of life (HRQOL) among spouse caregivers assisting service members and veterans (SMV) with comorbid uncomplicated mild traumatic brain injury (MTBI) and post-traumatic stress disorder (PTSD). Spouse caregivers (N = 205) completed the Couples Satisfaction Index (CSI), 12 HRQOL measures, and the Mayo-Portland Adaptability Inventory 4th Edition (MPAI-4). T-scores were classified as "clinically elevated" using a cutoff of ≥60T. The sample was also classified into "Satisfied" (≥13.5, n = 113, 55.0%) or "Dissatisfied" (<13.5, n = 92, 44.0%) relationship categories. Using stepwise regression analysis, Anxiety, Family Disruption, Vigilance, Emotional Support, Feeling Trapped, and MPAI-4 Adjustment were identified as the strongest predictors of CSI total scores (p < 0.001), accounting for 41.6% of the variance. Squared semi-partial correlations revealed that 18.1% of the variance was shared across all six measures, with 7.8% to 1.5% of unique variance accounted for by each measure separately. When comparing the number of clinically elevated measures simultaneously, the Dissatisfied group consistently had a higher number of clinically elevated scores compared to the Satisfied group (e.g., 3-or-more clinically elevated scores: Dissatisfied = 40.2%, Satisfied = 8.8%, OR = 6.93, H = 0.76). Caring for a SMV with comorbid TBI and PTSD can have a profound impact on the spouse caregiver's HRQOL, relationship satisfaction, and family functioning. The findings from the current study continue to support the need for family involvement in the SMV's treatment plan, but more effort is needed to integrate behavioral health treatment that focuses on the family member's own issues into military TBI and PTSD systems of care.

En este estudio se analizó la satisfacción con la relación y la calidad de vida relacionada con la salud entre cónyuges cuidadores que asisten a miembros del servicio militar y veteranos con lesión cerebral traumática leve sin complicaciones concomitante con trastorno por estrés postraumático. Los cónyuges cuidadores (N=205) completaron el Índice de satisfacción de las parejas (Couples Satisfaction Index, CSI), la Encuesta de 12 ítems sobre la calidad de vida relacionada con la salud (12 HRQQL) y la Encuesta de Adaptabilidad Mayo-Portland 4.ª edición (Mayo-Portland Adaptability Inventory 4th Edition, MPAI-4). Los puntajes T se clasificaron en "clínicamente elevados" usando un valor de corte de ≥60T. La muestra también se clasificó en categorías de relaciones "satisfechas" (>13.5, n=113, 55.0%) o "insatisfechas" (<13.5, n=92, 44.0%). Utilizando un análisis de regresión paso a paso, se identificaron la ansiedad, la interrupción familiar, la vigilancia, el apoyo emocional, la sensación de estar atrapado y la adaptación de la MPAI-4 como los factores pronósticos más fuertes de los puntajes totales del CSI (p<.001), que representaron el 41.6% de la varianza. Las correlaciones semiparciales al cuadrado revelaron que el 18.1% de la varianza se compartió entre las seis medidas, con una varianza única de 7.8% a 1.5% representada por cada medida separadamente. Cuando se comparó el número de medidas clínicamente elevadas de manera simultánea, el grupo insatisfecho tuvo sistemáticamente un número más alto de puntajes clínicamente elevados en comparación con el grupo satisfecho (p. ej.: 3 o más puntajes clínicamente elevados: insatisfecho=40.2%, satisfecho=8.8%, OR=6.93, H=.76). cuidar a un miembro del servicio militar o a un veterano con lesión cerebral traumática leve y trastorno por estrés postraumático concomitantes puede afectar enormemente la calidad de vida relacionada con la salud del cónyuge cuidador, la satisfacción con la relación y el funcionamiento familiar. Los resultados del presente estudio continúan respaldando la necesidad de la participación familiar en el plan de tratamiento del miembro del servicio militar o veterano, pero se necesita más esfuerzo para integrar un tratamiento de salud conductual que se centre en los problemas propios del familiar en los sistemas de atención de militares con lesión cerebral traumática leve y trastorno por estrés postraumático.

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.

Risk Factors Associated With the Prescription of Opioids Among Service Members Following a First Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate factors impacting opioid receipt among active-duty service members (SMs) following a first mild traumatic brain injury (mTBI). SETTING: Active-duty SMs receiving care within the Military Health System. PARTICIPANTS: In total, 14 757 SMs who have sustained an initial mTBI, as documented within electronic health records (EHRs), between 2016 and 2017. DESIGN: A retrospective analysis of EHR metadata. MAIN MEASURES: Multivariable logistic regression assessed factors impacting opioid receipt and initiation. Factors include demographics, military characteristics, and preexisting clinical conditions, including prior opioid prescription. RESULTS: Of the sample population, 33.4% (n = 4927) were prescribed opioids after their initial mTBI, of which, 60.6% (n = 2985) received opioids for the first time following injury. Significant risk factors associated with the increased probability of opioid receipt included age, gender, and preexisting behavioral health and musculoskeletal conditions. Military characteristics also exhibited changes in the probability of opioid receipt, both among initiation and new prescription. No changes were observed among race, nor among those with preexisting headaches or migraines. CONCLUSION: Despite concerns about the negative impact on recovery, the prescribing of opioids is common in this population of active-duty SMs first diagnosed with an mTBI. As several demographic and preexisting health conditions are factors in the receipt of opioids post-mTBI, the entire medical history of these patients should be considered prior to prescription. Understanding these factors may further inform policy for opioid use in the Military Health System.

Intracranial Abnormalities Are Associated With Fewer Self-Reported Symptoms in Military Service Members Following Moderate-to-Severe Traumatic Brain Injury.

OBJECTIVE: This study examined the relationship between intracranial abnormalities (ICAs) and self-reported neurobehavioral and posttraumatic stress (PTS) symptoms in members of the military with moderate-to-severe traumatic brain injury (msTBI). METHOD: Participants included 539 members of the US military with nonpenetrating msTBI. Self-reported neurobehavioral and PTS symptoms were assessed using the Neurobehavioral Symptom Inventory and the PTSD Checklist-Civilian Version. ICAs were categorized as present/absent (by subtype) based upon medical record review. Spearman rank-order correlations and stepwise multiple regression analyses examined univariate and combined predictive relationships between ICAs and self-reported symptoms. RESULTS: The presence of any ICA was associated with reduced self-reported neurobehavioral and PTS symptoms. ICA-associated reductions were largest for PTS, followed by affective and cognitive neurobehavioral symptoms, and relatively weak for somatic/sensory and vestibular symptoms. Effects of different types of ICAs were comparable. Greater time since injury was related to greater symptom report, whereas duration of loss of consciousness and posttraumatic amnesia were not consistently related to self-reported symptoms. CONCLUSIONS: Results suggest that ICAs are associated with suppression of reported PTS and neurobehavioral symptoms-potentially via reduction in self-awareness. These findings support comprehensive, objective evaluation to identify impairments in self-awareness and functioning in msTBI patients.

The effect of mTBI and PTSD symptoms on computerized cognitive performance: Results from a sample of treatment-seeking active duty US service members.

TBI and PTSD occur in a significant number of service members and can each result in considerable distress and cognitive challenges. Past research has established the individual impact of mild TBI (mTBI) and PTSD on cognitive performance; however, findings regarding the combined effects of mTBI and PTSD on cognitive performance are inconsistent. The present study examined the potentially synergistic effects of mTBI and PTSD symptoms on cognitive performance in a sample of 180 treatment-seeking active duty service members. As part of a larger clinical study, participants completed several self-report measures and an objective cognitive assessment via computer-based testing. Compared to norms, service members with mTBI-only, PTSD-symptoms-only, and comorbid TBI and PTSD performed significantly worse on cognitive tests, and there was a significant effect of group on cognitive performance, even when controlling for performance validity. Notably, individuals experiencing both mTBI and PTSD performed worse than those with either condition alone; service members with mTBI-only and those with PTSD symptoms-only did not differ. Findings further illustrate the complexity of the relationship between these two conditions, indicating comorbid mTBI and PTSD may represent a unique challenge to cognitive performance. Additional research is needed to clarify their combined impact on post-injury functioning.

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

BACKGROUND: There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury. METHODS: We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models. RESULTS: The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (µ = - 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (µ = - 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (µ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (µ = - 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (µ = 1859.60 pg/ml; s.e. = 1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases. CONCLUSION: The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.