Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024.

Healthy Days at Home Among Older Medicare Beneficiaries With Traumatic Brain Injury Requiring Inpatient Rehabilitation.

OBJECTIVE: The objectives of this study were to characterize and identify correlates of healthy days at home (HDaH) before and after TBI requiring inpatient rehabilitation. Setting: Inpatient hospital, nursing home, and home health services. PARTICIPANTS: Average of n= 631 community-dwelling fee-for-service age 66+ Medicare beneficiaries across 30 replicate samples who were hospitalized for traumatic brain injury (TBI) between 2012 and 2014 and admitted to an inpatient rehabilitation facility (IRF) within 72 hours of hospital discharge. DESIGN: Retrospective study using data from Medicare claims supplemented with data from the National Trauma Databank. MAIN MEASURES: The primary outcome, HDaH, was calculated as time alive not using inpatient hospital, nursing home, and home health services in the year before TBI hospitalization and after IRF discharge. RESULTS: We found HDaH declined from 93.2% in the year before TBI hospitalization to 65.3% in the year after IRF discharge (73.6% among survivors only). Most variability in HDaH was: (1) in the first 3 months after discharge and (2) by discharge disposition, with persons discharged from IRF to another acute hospital having the worst prognosis for utilization and death. In negative binomial regression models, the strongest predictors of HDaH in the year after discharge were rehabilitation Functional Independence Measure mobility score (ß = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score (ß = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors (ß = - 0.37; 95% CI, -0.66 to -0.07). CONCLUSION: In this study, among community-dwelling older adults with TBI, we found a notable decrease in the proportion of time spent alive at home without higher-level care after IRF discharge compared to before TBI. The finding that physical disability and comorbidities were the biggest drivers of healthy days alive in this population suggests that a chronic disease management model is required for older adults with TBI to manage their complex health care needs.

The Effects of Repetitive Head Impact Exposure on Mental Health Symptoms Following Traumatic Brain Injury.

OBJECTIVE: This study aimed to characterize the types and timing of repetitive head impact (RHI) exposures in individuals with moderate to severe traumatic brain injury (TBI) and to examine the effects of RHI exposures on mental health outcomes. SETTING: TBI Model Systems National Database. PARTICIPANTS: 447 patients with moderate to severe TBI who reported RHI exposure between 2015 and 2022. DESIGN: Secondary data analysis. MAIN MEASURES: RHI exposures reported on the Ohio State University TBI Identification Method (OSU TBI-ID) were characterized by exposure category, duration, and timing relative to the index TBI. Mental health outcomes were evaluated at the 5-year follow-up assessment using the Patient Health Questionnaire-9 (PHQ-9) for depression symptoms and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. RESULTS: The majority of RHI exposures were sports-related (61.1%), followed by other causes (20.8%; including falls), repetitive violence/assault (18.8%), and military exposures (6.7%). Males predominantly reported sports and military exposures, while a larger proportion of females reported violence and falls. Sports exposures were most common before the index TBI, while exposures from falls and violence/abuse were most common after TBI. RHI exposures occurring after the index TBI were associated with higher levels of depression (ß = 5.05; 95% CI, 1.59-8.50) and anxiety (ß = 4.53; 95% CI, 1.02-8.05) symptoms than exposures before the index TBI. CONCLUSION: The findings emphasize the need to consider RHI exposures and their interaction with TBI when assessing mental health outcomes. Understanding the prevalence and challenges associated with RHI post-TBI can inform targeted interventions and improve the well-being of individuals with TBI. Preventive measures and ongoing care should be implemented to address the risks posed by RHI, particularly in individuals with prior TBI, especially surrounding fall and violence/abuse prevention.

Patient and Caregiver Satisfaction With the Brain Injury Rehabilitation: Improving the Transition Experience (BRITE) Intervention.

OBJECTIVE: To ascertain patient and caregiver satisfaction with an individualized case management intervention to improve transition from inpatient rehabilitation care to the community after traumatic brain injury (TBI). SETTING: Participants from 6 National Institute on Disability, Independent Living, and Rehabilitation Research-funded TBI Model Systems sites in the United States. PARTICIPANTS: Adult, English-speaking patients with TBI who had moderate-to-severe TBI and were discharged from a TBI Model Systems site and who were in the intervention arm of the Brain Injury Rehabilitation: Improving the Transition Experience pragmatic clinical trial, as well as their caregivers. DESIGN: A survey of participants in the intervention arm, which included an individualized case management program administered by a TBI Care Manager (TCM) who facilitated resource connection, education, and support. MAIN MEASURES: Satisfaction with intervention was measured through Likert-scaled and open-ended questions. The survey was administered verbally through telephone, audio-recorded, and transcribed. Descriptive statistics were calculated for categorical variables, and content analysis was conducted for open-ended responses. RESULTS: Patient and caregiver participants were satisfied with the intervention and highlighted the benefits of the interpersonal and practical support provided by the TCM. Participants identified the need for a more intensive intervention and clear expectations of the TCM role, as well as gaps in available medical and rehabilitation services in the community, as areas for improvement. CONCLUSION: Patients with TBI and their caregivers reported satisfaction with the individualized case management program in supporting their transition from inpatient rehabilitation to the community. Further research is needed to understand the impact on outcomes.

Characterizing Extreme Phenotypes for Pain Interference in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To define and characterize extreme phenotypes based on pain interference for persons with chronic pain following traumatic brain injury (TBI). SETTING: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. PARTICIPANTS: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. PRIMARY MEASURES: The Brief Pain Inventory (BPI) interference scale, sociodemographic, injury, functional outcome, pain, and treatment characteristics. RESULTS: Participants were predominantly male (73%), White (75%), middle-aged (mean 46 years), and who were injured in motor vehicle accidents (53%) or falls (20%). Extreme phenotypes were identified based on upper and lower 25th percentiles to create low-interference ( n = 441) and high-interference ( n = 431) extreme phenotypes. Bivariate comparisons found several sociodemographic, injury, function, pain, and treatment differences between extreme phenotype groups, including significant differences ( P < .001) on all measures of concurrent function with those in the low-interference extreme phenotype experiencing better function than those in the high-interference extreme phenotype. Lasso regression combined with logistic regression identified multivariable predictors of low- versus high-interference extreme phenotypes. Reductions in the odds of low- versus high-interference phenotypes were significantly associated with higher pain intensity (odds ratio [OR] = 0.33), having neuropathic pain (OR = 0.40), migraine headache (OR = 0.41), leg/feet pain (OR = 0.34), or hip pain (OR = 0.46), and more pain catastrophizing (OR = 0.81). CONCLUSION: Results suggest that for those who experience current chronic pain, there is high variability in the experience and impact of pain. Future research is needed to better understand how pain experience impacts individuals with chronic pain and TBI given that pain characteristics were the primary distinguishing factors between phenotypes. The use of extreme phenotypes for pain interference may be useful to better stratify samples to determine efficacy of pain treatment for individuals with TBI.

Characterizing Extreme Phenotypes for Perceived Improvement From Treatment in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To define and characterize extreme phenotypes based on perceived improvement in pain for persons with chronic pain following traumatic brain injury (TBI). SETTING: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. PARTICIPANTS: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. PRIMARY MEASURES: The Patient's Global Impression of Change (PGIC) related to pain treatment. Sociodemographic, injury, functional outcome, pain, and pain treatment characteristics. RESULTS: Participants were mostly male (73%), White (75%), middle-aged (mean 46 years), injured in motor vehicle accidents (53%), or falls (20%). Extreme phenotypes were created for an extreme improvement phenotype ( n = 512, 29.8%) defined as "moderately better" or above on the PGIC and an extreme no-change group ( n = 290, 16.9%) defined as no change or worse. Least absolute shrinkage and selection operator (LASSO) regression combined with logistic regression identified multivariable predictors of improvement versus no-change extreme phenotypes. Higher odds of extreme improvement phenotype were significantly associated with being female (odds ratio [OR] = 1.85), married versus single (OR = 2.02), better motor function (OR = 1.03), lower pain intensity (OR = 0.78), and less frequent pain, especially chest pain (OR = 0.36). Several pain treatments were associated with higher odds of being in the extreme improvement versus no-change phenotypes including pain medication (OR = 1.85), physical therapy (OR = 1.51), yoga (OR = 1.61), home exercise program (OR = 1.07), and massage (OR = 1.69). CONCLUSION: Investigation of extreme phenotypes based on perceived improvement with pain treatment highlights the ability to identify characteristics of individuals based on pain treatment responsiveness. A better understanding of the biopsychosocial characteristics of those who respond and do not respond to pain treatments received may help inform better surveillance, monitoring, and treatment. With further research, the identification of risk factors (such as pain intensity and frequency) for treatment response/nonresponse may provide indicators to prompt changes in care for individuals with chronic pain after TBI.

Characterization and Treatment of Chronic Pain After Traumatic Brain Injury-Comparison of Characteristics Between Individuals With Current Pain, Past Pain, and No Pain: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To estimate the prevalence of chronic pain after traumatic brain injury (TBI) and identify characteristics that differ from those without chronic pain. SETTING: Community. PARTICIPANTS: A total of 3804 TBI Model Systems (TBIMS) participants who completed the Pain Survey at TBIMS follow-up. DESIGN: A multisite, cross-sectional observational cohort study. MAIN OUTCOME MEASURES: Functional outcomes, pain experience, and treatment. RESULTS: 46% reported current chronic pain, 14% reported past (post-injury) chronic pain, and 40% reported no chronic pain. Bivariate differences in sociodemographic and injury characteristics between the 3 pain groups were generally small in effect size, reflecting little clinical difference. However, medium effect sizes were seen for all functional outcomes, such that individuals with current chronic pain had worse functional outcomes compared with individuals in the past pain or no pain groups. Treatment utilization rates were higher for individuals with current chronic pain compared with past pain, with medical treatments being most frequently utilized. Individuals with past pain perceived more improvement with treatment than did those with current chronic pain as represented by a large effect size. CONCLUSIONS: Chronic pain affects approximately 60% of those living with TBI. The implications of chronic pain for functional outcomes support inclusion of pain metrics in prognostic models and observational studies in this population. Future research is needed to proactively identify those at risk for the development of chronic pain and determine the efficacy and access to pain treatment.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18-86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

The neuropathology of intimate partner violence.

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline.

Accumulating data suggest that cerebrovascular disease contributes to Alzheimer's disease pathophysiology and progression toward dementia. Cerebral amyloid angiopathy is a form of cerebrovascular pathology that results from the build-up of ß-amyloid in the vessel walls. Cerebral amyloid angiopathy commonly co-occurs with Alzheimer's disease pathology in the ageing brain and increases the risk of Alzheimer's disease dementia. In the present study, we examined whether cerebral amyloid angiopathy influences tau deposition and cognitive decline independently or synergistically with parenchymal ß-amyloid burden. Secondly, we examined whether tau burden mediates the association between cerebral amyloid angiopathy and cognitive decline. We included data from autopsied subjects recruited from one of three longitudinal clinical-pathological cohort studies: the Rush Memory and Aging Project, the Religious Orders Study and the Minority Aging Research Study. Participants completed annual clinical and cognitive evaluations and underwent brain autopsy. Cerebral amyloid angiopathy pathology was rated as none, mild, moderate or severe. Bielschowsky silver stain was used to visualize neuritic ß-amyloid plaques and neurofibrillary tangles. We used linear regression and linear mixed models to test independent versus interactive associations of cerebral amyloid angiopathy and neuritic plaque burden with tau burden and longitudinal cognitive decline, respectively. We used causal mediation models to examine whether tau mediates the association between cerebral amyloid angiopathy and cognitive decline. The study sample included 1722 autopsied subjects (age at baseline = 80.2 ± 7.1 years; age at death = 89.5 ± 6.7 years; 68% females). Cerebral amyloid angiopathy interacted with neuritic plaques to accelerate tau burden and cognitive decline. Specifically, those with more severe cerebral amyloid angiopathy pathology and higher levels of neuritic plaque burden had greater tau burden and faster cognitive decline. We also found that tau mediated the association between cerebral amyloid angiopathy and cognitive decline among participants with higher neuritic plaque burden. In summary, more severe levels of cerebral amyloid angiopathy and higher parenchymal ß-amyloid burden interacted to promote cognitive decline indirectly via tau deposition. These results highlight the dynamic interplay between cerebral amyloid angiopathy and Alzheimer's disease pathology in accelerating progression toward dementia. These findings have implications for Alzheimer's disease clinical trials and therapeutic development.

Sex-specific effects of microglial activation on Alzheimer's disease proteinopathy in older adults.

Females show a disproportionate burden of Alzheimer's disease pathology and higher Alzheimer's disease dementia prevalences compared to males, yet the mechanisms driving these vulnerabilities are unknown. There is sexual dimorphism in immunological functioning, and neuroimmune processes are implicated in Alzheimer's disease genesis. Using neuropathology indicators from human brain tissue, we examined the mediational role of microglial activation on the relationship between amyloid and tau and how it differs by sex. 187 decedents (64% female; 89 mean age at death; 62% non-demented) from the Rush Memory and Aging Project completed neuropathological evaluations with brain tissue quantified for microglial activation, amyloid-ß and tau. Proportion of morphologically activated microglia was determined via immunohistochemistry (HLA-DP-DQ-DR) and morphological staging (stage I, II or III). Amyloid-ß and tau burden were quantified via immunohistochemistry (M00872 or AT8, respectively). Using causal counterfactual modelling, we estimated the mediational effect of microglial activation on the amyloid-ß to tau relationship in the whole sample and stratified by sex (amyloid-ß â†’ microglial activation → tau). Alternative models tested the role of microglia activation as the precipitating event (microglial activation → amyloid-ß â†’ tau). Microglial activation significantly mediated 33% [95% confidence interval (CI) 10-67] of the relationship between amyloid-ß and tau in the whole sample; stratified analyses suggested this effect was stronger and only statistically significant in females. 57% (95% CI 22-100) of the effect of amyloid-ß on tau was mediated through microglial activation in females, compared to 19% (95% CI 0-64) in males. Regional analyses suggested that mediational effects were driven by greater cortical versus subcortical microglial activation. Relationships were independent of cerebrovascular disease indices. Alternative models suggested that in females, microglial activation was a significant exposure both preceding the amyloid-ß to tau relationship (mediational effect: 50%, 95% CI 23-90) and directly related to tau burden (microglia direct effect: 50%, 95% CI 10-77). By contrast, in males, only the direct effect of microglial activation to tau reached significance (74%, 95% CI 32-100) (mediational effect: 26%, 95% CI 0-68). Our models suggest a reciprocal, bidirectional relationship between amyloid-ß and microglial activation that significantly accounts for tau burden in females. By contrast, in males, direct independent (non-mediational) relationships between microglial activation or amyloid-ß with tau were observed. Microglial activation may be disproportionately important for Alzheimer's disease pathogenesis in females. Determining sex-specific vulnerabilities to Alzheimer's disease development both inform fundamental pathophysiology and support precision health approaches for this heterogeneous disease.

Effect of Post-traumatic Amnesia Duration on Traumatic Brain Injury (TBI) First Year Hospital Costs: A Veterans Affairs Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the association between severity of traumatic brain injury (TBI) as measured by duration of post-traumatic amnesia (PTA) and first year hospitalization costs for service members and veterans (SMVs) treated for TBI at Polytrauma Rehabilitation Centers (PRCs) within the Veterans Health Administration (VHA). DESIGN: Multivariable models of merged datasets from the VA TBI Model Systems (VA TBIMS) national database containing TBI clinical characterization including PTA with VHA hospital cost data. SETTING: Five VA PRCs. PARTICIPANTS: VA TBIMS participants with known PTA who received inpatient rehabilitation within 1 year of their TBI at any of 5 PRCs between 2010 and 2020 (N=717). INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Total, acute care, rehabilitation, intensive care unit (ICU), and surgery costs across all VA hospitals. RESULTS: A total of 717 SMVs (mean age 36.9 years, 94.1% men, 76.8% non-Hispanic White, 7.8% active duty) met inclusion criteria for the unadjusted analyses. Unadjusted mean total hospital costs in the first-year post TBI were approximately $201,214 higher for those with PTA duration ≥24 hours ($351,157) than PTA <24 hours ($149,943). In adjusted models (n=583), each additional day of PTA duration incrementally increased total ($1453), rehabilitation ($1324), ICU ($78), and surgery ($39) costs. Other significant covariates included age, acute care length of stay, Disability Rating Scale on rehabilitation admission, penetrating violent cause of injury, and drug abuse. CONCLUSIONS: This study demonstrates that PTA as a quantitative measure of TBI severity significantly affects first-year hospitalization costs of SMVs treated at PRCs. Each additional day of PTA was associated with higher total, rehabilitation, ICU, and surgery costs. Mean first year hospital costs were also found to exceed the highest budget allocation to VHA facilities for a veteran treated at a PRC. These findings have possible implications for hospital care provision for those receiving inpatient rehabilitation in VHA settings.

Identification of Factors in Moderate-Severe TBI Related to a Functional Decline in Cognition Decades After Injury.

OBJECTIVE: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury. DESIGN: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI. SETTING: TBI Model Systems Centers. PARTICIPANTS: Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): FIM Cognitive Scale. Injury characteristics such as timing and features pertaining to severity and health-related factors (eg, alcohol use, socioeconomic status) were examined to discriminate stable from declining participants on the FIM Cognitive Scale using logistic regression. RESULTS: At 20 years post-injury, there was a low base rate of FIM Cognitive decline (11%, n=78), with most being stable or having meaningful improvement (89%, n=654). Older age at injury, longer duration of post-traumatic amnesia, and presence of repetitive seizures were significant predictors of FIM Cognitive decline in the final model (area under the curve=0.75), while multiple health-related factors that can represent independent co-morbidities or possible consequences of injury were not. CONCLUSION(S): The strongest contributors to reported functional decline in cognitive activities later-in-life were related to acute characteristics of m-sTBI and experiencing post-traumatic seizures. Future studies are needed integrating functional with performance-based cognitive assessments to affirm conclusions and identify the timeline and trajectory of cognitive decline.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Distal and Proximal Predictors of Rehospitalization Over 10 Years Among Survivors of TBI: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To describe the rates and causes of rehospitalization over a 10-year period following a moderate-severe traumatic brain injury (TBI) utilizing the Healthcare Cost and Utilization Project (HCUP) diagnostic coding scheme. SETTING: TBI Model Systems centers. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI. DESIGN: Prospective cohort study. MAIN MEASURES: Rehospitalization (and reason for rehospitalization) as reported by participants or their proxies during follow-up telephone interviews at 1, 2, 5, and 10 years postinjury. RESULTS: The greatest number of rehospitalizations occurred in the first year postinjury (23.4% of the sample), and the rates of rehospitalization remained stable (21.1%-20.9%) at 2 and 5 years postinjury and then decreased slightly (18.6%) at 10 years postinjury. Reasons for rehospitalization varied over time, but seizure was the most common reason at 1, 2, and 5 years postinjury. Other common reasons were related to need for procedures (eg, craniotomy or craniectomy) or medical comorbid conditions (eg, diseases of the heart, bacterial infections, or fractures). Multivariable logistic regression models showed that Functional Independence Measure (FIM) Motor score at time of discharge from inpatient rehabilitation was consistently associated with rehospitalization at all time points. Other factors associated with future rehospitalization over time included a history of rehospitalization, presence of seizures, need for craniotomy/craniectomy during acute hospitalization, as well as older age and greater physical and mental health comorbidities. CONCLUSION: Using diagnostic codes to characterize reasons for rehospitalization may facilitate identification of baseline (eg, FIM Motor score or craniotomy/craniectomy) and proximal (eg, seizures or prior rehospitalization) factors that are associated with rehospitalization. Information about reasons for rehospitalization can aid healthcare system planning. By identifying those recovering from TBI at a higher risk for rehospitalization, providing closer monitoring may help decrease the healthcare burden by preventing rehospitalization.

Cognitive Performance, Depression, and Anxiety 1 Year After Traumatic Brain Injury.

OBJECTIVES: To evaluate associations between depression, anxiety, and cognitive impairment among individuals with complicated mild to severe traumatic brain injury (TBI) 1 year after injury. SETTING: Multiple inpatient rehabilitation units across the United States. PARTICIPANTS: A total of 498 adults 16 years and older who completed inpatient rehabilitation for complicated mild to severe TBI. DESIGN: Secondary analysis of a prospective, multicenter, cross-sectional observational cohort study. MAIN MEASURES: Assessments of depression (Traumatic Brain Injury Quality of Life [TBI-QOL] Depression) and anxiety (TBI-QOL Anxiety) as well as a telephone-based brief screening measure of cognitive functioning (Brief Test of Adult Cognition by Telephone [BTACT]). RESULTS: We found an inverse relationship between self-reported depression symptoms and the BTACT Composite score (ß = -0.18, P < .01) and anxiety symptoms and the BTACT Composite score (ß = -0.20, P < .01). There was no evidence this relationship varied by injury severity. Exploratory analyses showed depression and anxiety were negatively correlated with both BTACT Executive Function factor score and BTACT Memory factor score. CONCLUSIONS: Both depression and anxiety have a small but significant negative association with cognitive performance in the context of complicated mild to severe TBI. These findings highlight the importance of considering depression and anxiety when interpreting TBI-related neuropsychological impairments, even among more severe TBI.

A Network Analysis of the PART-O at 1 and 2 Years After TBI: A Veterans Affairs Model Systems Study.

OBJECTIVE: The construct of participation after traumatic brain injury (TBI) can be difficult to operationalize. Psychometric network analysis offers an empirical approach to visualizing and quantifying the associations between activities that comprise participation, elucidating the relations among the construct's components without assuming the presence of a latent common cause and generating a model to inform future measurement methods. The current research applied psychometric network analysis to the Participation Assessment with Recombined Tools-Objective (PART-O) within a sample of service members and veterans (SM/Vs) with a history of TBI at 1 and 2 years ( T1 and T2 ) postinjury. PARTICIPANTS: Participants ( N = 663) were SM/Vs with a history of TBI who completed comprehensive inpatient rehabilitation services at a Department of Veterans Affairs (VA) Polytrauma Rehabilitation Center (PRC). SETTING: Five VA PRCs. DESIGN: Cross-sectional, retrospective analysis of data from the VA TBI Model Systems study. MAIN MEASURES: PART-O. RESULTS: Network analysis demonstrated that the PART-O structure was generally consistent over time, but some differences emerged. The greatest difference observed was the association between "spending time with friends" and "giving emotional support" to others. This association was more than twice as strong at T2 as at T1 . The "out of the house" item was most central, as demonstrated by dense connections within its own subscale (Out and About) and items in other subscales (ie, Social Relations and Productivity). When examining items connecting the 3 subscales, the items related to giving emotional support, internet use, and getting out of the house emerged as the strongest connectors at T1 , and the internet was the strongest connector at T2 . CONCLUSION: Providing emotional support to others is associated with greater participation across multiple domains and is an important indicator of recovery. Being out and about, internet use, and engagement in productive activities such as school and work shared strong associations with Social Relations. Network analysis permits visual conceptualization of the dynamic constructs that comprise participation and has the potential to inform approaches to measurement and treatment.

Relative contribution of acute cognitive and motor functioning on community integration 1 year after moderate-severe TBI.

OBJECTIVES: The objective of this study was to understand the relative contribution of acute motor versus cognitive functioning on community integration 1 year after moderate-severe traumatic brain injury (TBI). METHODS: Secondary data analysis of 779 participants in the TBI Model Systems National Database who experienced a moderate-severe TBI requiring inpatient rehabilitation. Participants were categorized into four groups: low motor/low cognition, low motor/high cognition, high motor/low cognition, or high motor/high cognition. Community integration outcomes measured 1 year post-TBI included the Participation Assessment with Recombined Tools-Objective (PART-O), driving status, Supervision Rating Scale, residence, re-injury, and employment status. RESULTS: Participants with both high motor/high cognition had higher scores on the PART-O total score (p < 0.001), living independently (p = 0.023), living in a private residence (p = 0.002), and being employed (p = 0.026) at 1 year. Participants with high motor/high cognition and high motor/low cognition had higher odds of driving (p = 0.001 and p = 0.034, respectively) when compared to low motor/low cognition. All groups relative to the low motor/low cognition group had higher odds of being re-injured. DISCUSSION AND CONCLUSIONS: High motor and high cognitive function at rehabilitation are associated with favorable community integration outcomes 1 year post-injury, though greater participation afforded by high function may confer elevated risk of re-injury.

Traumatic brain injury history and baseline symptoms outweigh sex differences for risk of concussion in a sample of collegiate athletes.

OBJECTIVE: To test the hypothesis that a history of traumatic brain injury (TBI) prior to the collegiate pre-season is associated with risk for re-injury. We also investigate sex differences, cognitive functioning, and self-reported concussion symptoms and their associations with concussion risk. METHODS: A longitudinal cohort study consisting of collegiate athletes (n = 212) who completed consecutive preseason evaluations (P1 and P2) between 2012 and 2015, averaging 12.9 (SD = 4.2) months apart. RESULTS: There were 40 new concussions recorded between P1 and P2, 21 (53%) of which were among athletes who reported a lifetime history of mild TBI/concussion at P1. New P1-P2 concussions occurred in 24% of female athletes (n = 23) and 15% of male athletes (n = 17). History of TBI and female sex were significant predictors of new concussion between P1 and P2; however, in adjusted models, the inclusion of Impulse Control and PCSS Total symptom scores attenuated the effect of sex on the risk for new injury. CONCLUSION: Collegiate athletes with a lifetime history of TBI had a significantly higher risk of sustaining a subsequent concussion. Pre-season emotional and somatic symptomology may contribute to incident concussion risk. The findings highlight the importance of considering lifetime head injury exposure and baseline symptomatology when interpreting sex differences and evaluating concussion risk.