History Of Traumatic Brain Injury Research Articles

The weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes

ABSTRACT Background Chronic neurologic deficits from traumatic brain injury (TBI) and subsequent infectious encephalitis are poorly characterized. Methods Using TriNetX database we queried patients 18 years or older with a confirmed diagnosis of encephalitis between 2016 and 2024. Patient cohorts included those with a diagnosis of TBI at least one month before encephalitis (N = 1,038), those with a diagnosis of a TBI anytime before encephalitis (N = 1,886), and those with encephalitis but no TBI, (N = 45,210; N = 45,215). A murine model of controlled cortical impact (CCI) injury and Venezuelan equine encephalitis virus (VEEV) infection was used to reflect the clinical model, followed by extracting hippocampal tissue for bulk RNA sequencing and analysis. Results Patients with a TBI history at least one month before infectious encephalitis have an increased risk of mortality, epilepsy, and dementia or delirium. Bulk RNA sequencing of the hippocampus from mice subjected to CCI injury and VEEV infection demonstrated that key pathways, specifically those involved in granzyme mediated cell death, were enriched compared to VEEV infection alone. Conclusion Our findings reveal that infectious encephalitis in patients with TBI history portends worse neurologic outcomes, and the hippocampus may be vulnerable to granzyme mediated cell death under these conditions.

Dementia and epilepsy without traumatic brain injury among subjects middle-aged females: a population-based case-control study.

Background: Although the association between dementia such as Alzheimer's disease and traumatic brain injury (TBI) is well established, there are significant knowledge gaps with respect to the perspective of dementia and epilepsy without TBI. Objective: We aimed to investigate the relationship between dementia and epilepsy in a population-based study of patients without history of TBI. Methods: This study included a random sample of 30,715 patients with no history of TBI, including 6143 with epilepsy as the study cohort and 24,572 without epilepsy as the comparison cohort. Stratified Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR), with 95% confidence interval, for the risk of developing dementia in the two cohorts. Results: Patients with epilepsy but no history of TBI had increased risk of dementia (adjusted HR = 1.84). For patients aged 55-64 years, the adjusted HR for dementia was 4.5-fold higher among females in the study cohort than among males. Additionally, this study revealed that risk of dementia among above 75-year population lowest than other age subgroups (adjusted HR = 1.45). Conclusions: The study demonstrated an association between dementia and epilepsy in the patients who had no history of TBI. The effect was pronounced in patients aged 55-64 years, especially in the female population, suggesting that epilepsy needs to be more intensively prevented and controlled in this age group.

Hypopituitarism Screening in Patients with Traumatic Brain Injury in the Primary Care Setting at the Minneapolis Veterans Affairs Health Care System.

Traumatic brain injury (TBI) is a significant health issue among veterans and poses a substantial risk for pituitary injury. Consensus guidelines recommend that patients who have sustained a TBI should undergo a baseline pituitary hormonal evaluation after the primary brain insult. Patients with abnormal screening test results or with symptoms of hypopituitarism should be referred to endocrinology for a full assessment. Currently, there are no reported data on the screening rates of hypopituitarism in veterans with TBI. This pilot study was conducted to determine the frequency of screening for hypopituitarism in veterans with TBI in a primary care clinic setting. We conducted a single-center retrospective cohort study of patients with a diagnosis of TBI who were seen by their primary care physicians at the Minneapolis Veteran Affairs Health Care System over a 1-year period. A random sample was generated using computerized random generator software of patient data, including demographics, TBI-related information, and pituitary hormone levels, which were collected from the panel of primary care providers. We used 2 sets of screening criteria, one by Ghigo etal. published in 2005, and the second by Tan etal. published in 2017, to define hypopituitarism screening adequacy in our cohort of TBI patients. Institutional Review Board approval was obtained. None of the 50 patients who met the criteria for screening based on the 2005 recommendations were screened for hypopituitarism. Only 2 of the 26 patients who met the criteria for screening based on the more recent 2017 recommendations were screened for hypopituitarism. We report that the screening rate for hypopituitarism in TBI patients is exceedingly low in the primary care setting, even with the less rigorous newer screening recommendations. Measures should be taken to improve screening of hypopituitarism to decrease morbidity and improve the quality of life in patients with a history of TBI.

Associations of Traumatic Brain Injury and Hearing: Results From the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

To examine associations of traumatic brain injury (TBI) with self-reported and clinical measures of hearing function. Four US communities. A total of 3176 Atherosclerosis Risk in Communities Study participants who attended the sixth study visit in 2016-2017, when hearing was assessed. Prospective cohort study. TBI occurring prior to the hearing assessment was defined using self-reported questions and "International Classification of Diseases-9th/10th Edition" (ICD-9/10) codes. Hearing function was assessed by self-reported questionnaires and clinically measured indices (audiometry [4-frequency pure tone average for each ear] and speech-in-noise testing). Linear, logistic, and multinomial logistic models adjusted for sociodemographics, vascular risk factors, and occupational noise exposure were used to examine associations. Participants were a mean age of 79years, 59% were female, 21% were of self-reported Black race, and 33% had a history of TBI (median time from first TBI to hearing assessment: 39years (25th-75th percentile=19-63years). Compared to participants without TBI, participants with prior TBI had higher age-adjusted prevalence of self-reported hearing loss (42.3% vs 35.3%), tinnitus (28.0% vs 23.8%), hearing aid use (23.4% vs 17.8%), pure tone average>40dB (30.6% vs 24.8%), and presence in the lowest quartile of speech-in-noise performance (27.6% vs 22.8%). With further adjustment, and particularly with adjustment for occupational noise exposure, associations with hearing measures were largely no longer statistically significant. In secondary analyses of associations of TBI frequency and severity with hearing function, results were similar to our main analyses, without evidence of dose-dependent associations. In this community-based cohort, prior TBI was associated with impaired hearing on both self-reported and clinically measured assessments, but these associations were attenuated after adjustment for occupational noise exposure. These results underscore the importance of the consideration of loud noise exposures, which may confound associations of TBI with hearing, in future studies.

Detecting Mild Traumatic Brain Injury after Combat Deployment: Agreement Between Veterans Health Administration Clinical System and LIMBIC-CENC Research Protocol.

Identifying historical mild traumatic brain injury (TBI) is important for many clinical care reasons; however, diagnosing mild TBI is inherently challenging and utility of screening is unknown. This study compares a standardized research process to an established clinical process for screening and diagnosis of historical mild TBI during combat deployment in a military/Veteran cohort. Using validated instruments, the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) prospective longitudinal study (PLS) screens for all potential concussive events (PCEs) and conducts structured concussion diagnostic interviews for each PCE. The Veterans Health Administration (VHA) systematically screens all Veterans with a post-9/11 combat deployment for historical TBI and offers a comprehensive TBI evaluation (CTBIE) for those who screen positive. This study evaluates the agreement between these two systems on both PCE and mild TBI identification during combat deployment and identifies features of Veterans who were negative clinically but positive in research. VHA TBI screen and CTBIE data were obtained from Veterans Affairs Informatics and Computing Infrastructure and linked to the LIMBIC-CENC PLS dataset. VHA screen positive for PCE was defined as a positive response for the first two VHA TBI screen questions of that query mechanism and immediate signs/symptoms of TBI. The PLS identified more positive PCE screens during combat deployment (86% vs. 41%) than the VHA PCE screen, and overall agreement was poor (kappa = 0.113). Participants had higher odds of being VHA negative/PLS positive on the PCE screen if they were of older age, female sex, had more years of military service, more months in combat deployment, officer rank, or <50% service-connected disability rating and lower odds if they had less education attainment, higher combat intensity, or higher Neurobehavioral Symptom Inventory scores. The LIMBIC-CENC PLS method also identified more Veterans with mild TBI during combat deployment compared with the VHA CTBIE (81% vs. 72%) with minimal overall agreement (kappa = 0.311). Participants had higher odds of being VHA negative/PLS positive for mild TBI diagnosis if they never married or were Air Force and had lower odds if they had higher combat intensity. The LIMBIC-CENC PLS research structured interview protocol identified higher rates of TBI than the VHA TBI assessment system both for positive PCE screens and positive mild TBI diagnosis during combat deployment. Agreement was far higher for TBI determinations compared with the PCE screening. Significant characteristics of PLS-positive/VHA-negative mismatches included demographic variables, military service variables, and current symptom levels. Further research is needed to better understand whether there is a clinical value to adjust the VHA TBI screening process and how these characteristics could be considered. Providers should be aware that some Veterans may have undocumented, positive mild TBI histories even if they underwent screening and/or CTBIE processes.

Normative Ranges for Oculomotor and Reaction Time Tests in U.S. Military Service Members and Veterans.

Oculomotor and reaction time tests are frequently used assessments of vestibular symptoms, traumatic brain injury (TBI), or other neurological disorders in both clinical and research contexts. When interpreting these tests it is important to have a reference interval (RI) as a comparison for what constitutes a typical/expected response; however, the current body of research has only limited information regarding normative ranges calculated according to established standards or for a military-specific sample. The purpose of the present study was to describe RIs for oculomotor and reaction time tests in a cohort of service members and veterans (SMVs) for use as comparators by clinicians and scientists. Descriptive. Participants were prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury Study. Only SMVs without a history of TBI or blast exposure were included in the RI calculations. The test paradigms included in this analysis were: smooth pursuit, prosaccades, antisaccades, saccades and reaction time, predictive saccades, optokinetic nystagmus, auditory reaction time, and visual reaction time. Nonparametric methods, based on the U.S. Food and Drug Administration's recognized consensus standards, were used to calculate 95% RIs. A comparison between the calculated RIs and those available from previously published research is provided. Summary statistics and RIs were calculated for 47 outcome parameters from 13 oculomotor and reaction time tests. Sample sizes and age ranges varied across outcome parameters depending on the availability of reference values for RI calculations. The sample sizes used to calculate RIs ranged from 51 to 69. The age of SMVs included in each RI ranged from 19 to 61 years with mean ages ranging from 37 to 39 years. Similarities/differences between the RIs in the present study and those in previously published research are highly dependent on the outcome parameter; however, in general, the RIs in the present study tended to be somewhat wider. The RIs provided in this paper can serve as comparisons for clinicians and scientists who are utilizing these oculomotor and reaction time testing paradigms in similar cohorts of patients or research participants.

Does Variation in Hospital Density and Social Deprivation Across Small Geographic Areas Play a Role in Perceived Barriers to Care Among People With Traumatic Brain Injury?

To examine the role of area-level variables (hospital density and social deprivation) in the experience of health care access and quality among individuals with traumatic brain injury. Online questionnaire of community dwelling individuals Participants: 300 individuals with a history of traumatic brain injury with loss of consciousness. Cross-sectional observational survey. Barriers to Care Questionnaire, Social Deprivation Index, Hospital Density. In an unadjusted regression model, less social deprivation and higher hospital density were associated with better perceived health care access and quality. After adjusting for personal factors of race, ethnicity, age, injury severity, food insecurity, and housing insecurity, the effect of social deprivation was fully attenuated whereas the effect of hospital density on health care access and quality remained significant. A model containing only the personal factors demonstrated reduced health care access and quality among individuals identifying as Hispanic. However, this effect was non-significant with the inclusion of the area-level contextual factors in a fully adjusted model. Higher area-level hospital density is associated with a reduction in perceived barriers to care among individuals with TBI. In addition, contextual, area-level data accounted for the reduced health care access and quality among Hispanic participants. Area-level data can provide explanatory value in the study of health disparities for people with TBI from underrepresented racial and ethnic groups.

Traumatic Brain Injury and Alzheimer's Disease Biomarkers: A Systematic Review of Findings from Amyloid and Tau Positron Emission Tomography.

Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.

The Relationship Between Psychopathology, Personality Traits, and a History of Traumatic Brain Injury.

To determine whether history of traumatic brain injury (TBI) is associated with psychopathology, and, in particular, substance use disorder (SUD) in young adults with a history of athletic participation. Observational study. University in the northeastern United States. A large (n = 534) and mixed sex (57% female) sample of varsity and club sport athletes older than 18 years. None. The Ohio State University Traumatic Brain Injury ID assessment and the Structured Clinical Interview for the diagnostic and statistical manual of mental disorders, fifth edition. Twenty-five percent of participants reported no history of head injuries, 32% reported 1 head injury, and 43% reported more than 1 head injury. Thirty-eight percent of participants had been diagnosed with 1 or more concussions. Twenty-eight percent of participants had a current psychiatric diagnosis and 49% had at least 1 lifetime diagnosis. Head injuries and concussions were significantly associated with the presence of lifetime psychiatric diagnosis and symptoms or diagnosis of alcohol or SUD. More head injuries were associated with symptoms of post-traumatic stress disorder. Higher number of self-reported head injuries and diagnosed concussions were associated with a lifetime history of psychopathology, and specifically, with alcohol and substance use disorders. These relationships are similar to those seen in the general population of adults. The relationships also raise several interesting questions about recovery from head injuries in young adult athletes.

White matter hyperintensities and headache in United States military veterans with mild traumatic brain injury.

The objective of this study was to examine the association between white matter hyperintensities and migraine-like headache in United States military veterans with a history of mild traumatic brain injury. White matter hyperintensities on magnetic resonance imaging (MRI) may be associated with migraine; however, little is currently known about the relationship between white matter hyperintensities and headache following mild traumatic brain injury in military veterans. This cross-sectional study consisted of a retrospective chart review of veterans from a Southeastern Department of Veterans Affairs polytrauma clinic who had a verified history of mild traumatic brain injury. Participants were included if they had undergone an MRI of the brain. Images were reviewed for the presence and severity of periventricular and deep white matter hyperintensities. Headache and migraine-like headache were defined based on responses from the Neurobehavioral Symptom Inventory. This cohort included 83 veterans, mostly consisting of males (78/83 [94%]) with a median (interquartile range [IQR]) age of 36 (13) years, who were a median (IQR) of 9 (8) years since their most recent mild traumatic brain injury. Most of the veterans reported experiencing migraine-like headache (67/83 [81%]). Periventricular white matter hyperintensities were identified on MRI among 35% (29/83) of the cohort, and deep white matter hyperintensities were identified on MRI of 25% (21/83) of the cohort. There was no association between the odds of displaying white matter hyperintensities and the presence of migraine-like headache (periventricular: unadjusted odds ratio [OR] 2.75, 95% confidence interval [CI] 0.71-10.6; deep white matter: OR 0.69, 95% CI 0.208-2.29; all p > 0.05), nor headache severity (periventricular: moderate headache OR 2.92, 95% CI 0.67-12.8; severe headache OR 3.11, 95% CI 0.77-12.6; deep white matter: moderate headache OR 1.44, 95% CI 0.358-5.8; severe headache OR 0.94, 95% CI 0.246-3.62; all p > 0.05). Our findings suggest that neither migraine-like headache nor severity of headache is associated with increased prevalence of white matter hyperintensities in veterans with a history of mild traumatic brain injury.

Primary Visual Pathway Changes in Individuals With Chronic Mild Traumatic Brain Injury

Individuals with mild traumatic brain injury (TBI) often report vision problems despite having normal visual acuity and fundus examinations. Diagnostics are needed for these patients. To determine if a battery of assessments or machine-learning approaches can aid in diagnosing visual dysfunction in patients with mild TBI. This prospective, observational, case-control study was conducted between May 2018 and November 2021. The study setting was at a level 1 trauma research hospital. Participant eligibility included adult males and females with recorded best-corrected visual acuity and normal fundus examination. Individuals in the case group had a history of mild TBI; controls had no history of TBI. Exclusion criteria included a history of ocular, neurological, or psychiatric disease, moderate-severe TBI, recent TBI, metal implants, age younger than 18 years, and pregnancy. Cases and controls were sex- and age-matched. Data analysis was performed from July 2023 to March 2024. History of mild TBI in the case group. The single-session visit included the Neurobehavioral Symptom Inventory and measurements of oculomotor function, optical coherence tomography, contrast sensitivity, visual evoked potentials, visual field testing, and magnetic resonance imaging. A total of 28 participants (mean [SD] age, 35.0 [12.8] years; 15 male [53.6%]) with mild TBI and 28 controls (mean [SD] age, 35.8 [8.5] years; 19 female [67.9%]) were analyzed. Participants with mild TBI showed reduced prism convergence test breakpoint (-8.38; 95% CI, -14.14 to -2.62; P = .008) and recovery point (-8.44; 95% CI, -13.82 to -3.06; P = .004). Participants with mild TBI also had decreased contrast sensitivity (-0.07; 95% CI, -0.13 to -0.01; P = .04) and increased visual evoked potential binocular summation index (0.32; 95% CI, 0.02-0.63; P = .02). A subset of participants exhibited reduced peripapillary retinal nerve fiber layer thickness, increased optic nerve/sheath size, and brain cortical volumes. Machine learning identified subtle differences across the primary visual pathway, including the optic radiations and occipital lobe regions, independent of visual symptoms. Results of this case-control study suggest that the visual system was affected in individuals with mild TBI, even in those who did not self-report vision problems. These findings support the utility of a battery of assessments or machine-learning approaches to accurately diagnose this population.

The Effect of Bilateral, Two-Level Cervical Sympathetic Chain Blocks on Specific Symptom Clusters for Traumatic Brain Injury, Independent of Concomitant PTSD Symptoms.

Background/Objectives: The aim of this study was to determine if performing ultrasound-guided, bilateral, two-level cervical sympathetic chain blocks (2LCSBs) (performed on subsequent days) improves symptoms associated with traumatic brain injury (TBI) that do not overlap with posttraumatic stress disorder (PTSD). Methods: A retrospective chart review was conducted between August 2022 and February 2023. We identified twenty patients who received bilateral 2LCSBs for PTSD and anxiety symptoms and who also had a history of TBI. Neurobehavioral Symptom Inventory (NSI) scores were collected at baseline, one week, and one month post treatment in 13 males and 7 females. A sub-analysis of the first ten questions of the NSI, which we identified as not overlapping with PTSD or anxiety symptoms, generated an NSI sub-score. Results: Out of 20 patients, all showed improvement in their NSI scores and NSI sub-scores. The NSI sub-scores had a baseline average of 15.45 (on a 40-point scale); the average score at one week post treatment was 8.30; and that at one month post treatment was 7.80. This represents a 49.51% improvement in TBI symptoms which did not overlap with PTSD or anxiety symptoms between baseline and one month. Conclusions: The use of bilateral 2LCSBs may be helpful in treating patients with TBI, regardless of the presence of comorbid PTSD symptoms.

The Association Between Traumatic Brain Injury and the Risk of Cognitive Decline: An Umbrella Systematic Review and Meta-Analysis.

There is currently increasing interest in the implication of traumatic brain injury (TBI) as a potential risk factor for long-term neurodegenerative conditions, such as dementia and Alzheimer's disease (AD). In this context, we performed a systematic review and meta-analysis to evaluate the association between TBI and the risk of dementia. A systematic search was performed across multiple electronic databases, including PubMed, Embase, and Cochrane Library, to identify relevant meta-analyses and cohort studies. Studies were included if they reported effect sizes (odds ratios [ORs] or relative risks [RRs]) for the association between TBI, its severity, and the risk of dementia or AD. Meta-analyses were performed using random-effects models to account for heterogeneity, and sensitivity analyses were conducted. A total of six studies were included in the analysis. The pooled results showed that TBI significantly increases the risk of dementia, with an overall odds ratio of 1.81 (95% CI: 1.53-2.14). Mild TBI was associated with a modest increase in dementia risk (OR = 1.96, 95% CI: 1.70-2.26), while moderate-to-severe TBI showed a stronger association (OR = 1.95, 95% CI: 1.55-2.45). In contrast, the association between TBI and AD was less consistent, with the pooled OR for AD being 1.18 (at 95% CI: 1.11-1.25) for mild TBI; however, in several studies, no significant association was observed (OR = 1.02, 95% CI: 0.91-1.15). The results also indicated substantial heterogeneity across studies, particularly in relation to AD outcomes. The findings from this umbrella meta-analysis confirm that TBI is a significant risk factor for dementia, with more severe TBIs conferring a higher risk. While mild TBIs also increase the risk of dementia, the effect is more pronounced in moderate-to-severe injuries. The evidence linking TBI to AD is less robust, with inconsistent findings across studies. Clinicians should consider long-term cognitive screening and management for individuals with a history of TBI, particularly those with moderate-to-severe injuries.

Risk of stroke after traumatic brain injury: a systematic review and meta-analysis.

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. There is a suggested association between TBI and stroke, emphasizing the need for increased medical monitoring post-trauma. We conducted a systematic review and meta-analysis to investigate the link between previous TBI and the future diagnosis of any type of stroke. A comprehensive search was conducted on PubMed, Google Scholar, and Cochrane Library to find eligible studies investigating the association between TBI and long-term risk of stroke. Out of 2,378 studies, 11 articles met the inclusion criteria for our meta-analysis. The pooled analysis showed that the patients who had a history of TBI were at greater risk for stroke than patients in the control group (random-effect HR = 1.59, 95% CI 1.37-1.85, p < 0.001, I2 = 97%). The risk of ischemic stroke in TBI patients was greater than in non-TBI patients (random-effect HR = 1.52, 95% CI 1.36-1.70, p < 0.001, I2 = 93%). Additionally, there is a strong correlation between TBI and hemorrhagic stroke (random-effect HR = 4.68, 95% CI 2.93-7.49, p < 0.001, I2 = 93%). Our results indicate that there is a relationship between TBI and long-term risk of stroke, regardless of the stroke type. The risk is elevated in the first months post-injury and continues to be high in the years following the trauma. Individuals with moderate to severe TBI face a higher risk of developing a post-TBI stroke than those with mild TBI.

Traumatic brain injury, posttraumatic stress disorder, and vascular risk are independently associated with white matter aging in Vietnam-Era veterans.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions-TBI history, PTSD, and vascular risk-and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition. We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance. Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p's >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p's <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052). Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

Differences in Brain Volume in Military Service Members and Veterans After Blast-Related Mild TBI

Blast-related mild traumatic brain injuries (TBIs), the "signature injury" of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear. To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members. Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in this analysis between 2014 and 2023. Participants were recruited from Veterans Affairs medical centers across the US; 774 veterans and active duty service members of the US military met eligibility criteria for this secondary analysis. Assessment dates were from January 6, 2015, to March 31, 2023; processing and analysis dates were from August 1, 2023, to January 15, 2024. All participants had combat exposure, and 82% had 1 or more lifetime mild TBIs with variable injury mechanisms. Regional brain volume was calculated using tensor-based morphometry on 3-dimensional, T1-weighted magnetic resonance imaging scans; history of TBI, including history of blast-related mild TBI, was assessed by structured clinical interview. Cognitive performance and psychiatric symptoms were assessed with a battery of validated instruments. We hypothesized that regional volume would be smaller in the blast-related mild TBI group and that this would be associated with cognitive performance. A total of 774 veterans (670 [87%] male; mean [SD] age, 40.1 [9.8] years; 260 [34%] with blast-related TBI) were included in the sample. Individuals with a history of blast-related mild TBI had smaller brain volumes than individuals without a history of blast-related mild TBI (which includes uninjured individuals and those with non-blast-related mild TBI) in several clusters, with the largest centered bilaterally in the superior corona radiata and subcortical gray and white matter (cluster peak Cohen d range, -0.23 to -0.38; mean [SD] Cohen d, 0.28 [0.03]). Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between blast-related mild TBI and performance on measures of working memory and processing speed. In this cohort study of 774 veterans and active duty service members, robust volume differences associated with blast-related TBI were identified. Furthermore, these volume differences significantly mediated the association between blast-related mild TBI and cognitive function, indicating that this pattern of brain differences may have implications for daily functioning.

Metabolic syndrome and mobility dysfunction in older adults with and without histories of traumatic brain injury: The mediating role of cognition.

Older adults are more susceptible than the general population to developing metabolic syndrome (i.e., three or more cardiovascular risk factors [MetS]), physical limitations, and traumatic brain injury (TBI). Recent research has demonstrated that cognition may moderate the negative association between MetS and mobility dysfunction in older adults. This study sought to determine if cognition mediates the relationship between MetS and mobility dysfunction and if this relationship differs in older adults with a history of TBI. Participants (N = 20,156) were from the National Alzheimer's Coordinating Center's Uniform Data Set. Mediation models were tested to assess if processing speed, executive functioning, immediate memory, and delayed memory would independently mediate the association between MetS and mobility dysfunction. Investigation of mediation models revealed that MetS had a significant indirect effect on mobility dysfunction through processing speed (b = .0674, 95% CI [.0412, .0953]) and executive functioning (b = .0354, 95% CI [.0228, .0493]). When TBI was included in the model as a moderator, MetS was not found to moderate the mediating effects of any of the cognitive variables. There were no significant indirect effects for immediate or delayed memory in either model. Findings elucidate potential pathways by which MetS contributes to mobility dysfunction in older adults through specific reductions in processing speed and executive functioning capabilities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comorbid treatment of traumatic brain injury and mental health disorders.

The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders. This article reviews the EHVP. The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans. This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all. Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.

Insomnia and Chronic Pain Mediate the Relationship Between Traumatic Brain Injury and Reduced Positive Airway Pressure Adherence Among Veterans.

To examine whether co-morbid insomnia, post-traumatic stress disorder (PTSD), depression, and chronic pain mediate the relationship between traumatic brain injury (TBI) and positive airway pressure (PAP) treatment adherence. One Veterans Health Administration (VHA) sleep medicine site. Veterans (n =8836) who were prescribed a modem-enabled PAP device. Secondary analysis of clinical data. We used path analysis to examine: (1) whether Veterans with a history of TBI were more likely to experience insomnia, PTSD, depression, and chronic pain; (2) in turn, whether Veterans with these co-morbid conditions exhibited lesser PAP adherence; and (3) whether Veterans with a history of TBI will exhibit lesser PAP adherence, even while accounting for such co-morbid conditions. Model estimates were adjusted for sociodemographic (eg, race/ethnicity) and clinical characteristics (eg, mask leakage). Health conditions were abstracted from the VHA medical record. PAP adherence was measured using average nightly use (hours). Among 8836 Veterans, 12% had a history of TBI. TBI history was not associated with PAP adherence when accounting for the presence of insomnia, PTSD, depression, and chronic pain. Indirect effect estimates indicated that a history of mild, moderate-severe, or unclassified TBI was associated with lesser PAP adherence, as mediated by the presence of co-morbid insomnia and chronic pain. Generally, TBI was associated with an increased likelihood of co-morbid insomnia, PTSD, depression, and chronic pain. In turn, insomnia and chronic pain, but not PTSD or depression, were associated with lesser PAP adherence. Our study offers empirical support for insomnia and chronic pain as potential explanatory mechanisms underlying the relationship between TBI history and suboptimal PAP adherence. While additional research is needed to confirm causality, findings offer preliminary evidence that can inform the development of tailored PAP adherence interventions for Veterans with TBI and obstructive sleep apnea.

Supplemental Material for Metabolic Syndrome and Mobility Dysfunction in Older Adults With and Without Histories of Traumatic Brain Injury: The Mediating Role of Cognition

Supplemental Material for Metabolic Syndrome and Mobility Dysfunction in Older Adults With and Without Histories of Traumatic Brain Injury: The Mediating Role of Cognition