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Shannon B Juengst,1,2 Raj G Kumar,3 Amy K Wagner3–5 1Department of Physical Medicine and Rehabilitation, 2Department of Rehabilitation Counseling, University of Texas Southwestern Medical Center, Dallas, TX, 3Department of Physical Medicine and Rehabilitation, 4Department of Neuroscience, 5Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA Abstract: Depression is one of the most common conditions to emerge after traumatic brain injury (TBI), and despite its potentially serious consequences it remains undertreated. Treatment for post-traumatic depression (PTD) is complicated due to the multifactorial etiology of PTD, ranging from biological pathways to psychosocial adjustment. Identifying the unique, personalized factors contributing to the development of PTD could improve long-term treatment and management for individuals with TBI. The purpose of this narrative literature review was to summarize the prevalence and impact of PTD among those with moderate to severe TBI and to discuss current challenges in its management. Overall, PTD has an estimated point prevalence of 30%, with 50% of individuals with moderate to severe TBI experiencing an episode of PTD in the first year after injury alone. PTD has significant implications for health, leading to more hospitalizations and greater caregiver burden, for participation, reducing rates of return to work and affecting social relationships, and for quality of life. PTD may develop directly or indirectly as a result of biological changes after injury, most notably post-injury inflammation, or through psychological and psychosocial factors, including pre injury personal characteristics and post-injury adjustment to disability. Current evidence for effective treatments is limited, although the strongest evidence supports antidepressants and cognitive behavioral interventions. More personalized approaches to treatment and further research into unique therapy combinations may improve the management of PTD and improve the health, functioning, and quality of life for individuals with TBI. Keywords: traumatic brain injury, depression, inflammation, antidepressants, rehabilitation

Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking. Thus, we generated a model to investigate how PTE after moderate-to-severe (ms)TBI affects TBI-associated impairments, limits activities and participation, and influences SWL. Of 5108 participants with msTBI enrolled into the National Institute for Disability, Independent Living, and Rehabilitation Research TBI Model Systems between 2010 and 2018 and with seizure-event data available at year-1 post-TBI, 1214 had complete outcome data and 1003 had complete covariate data used for analysis. We constructed a conceptual framework illustrating hypothesized interrelationships between year-1 PTE, driving status, functional independence measure (FIM), depression and anxiety, as well as year-2 participation, and SWL. We performed univariate and multivariable linear and logistic regressions. A covariate-adjusted structural equation model (SEM), using the lavaan package (R), assessed the conceptual framework's suitability in establishing PTE links with outcomes 1-2 years post-injury. Multiple parameters were evaluated to assess SEM fit. Year-1 PTE was correlated with year-1 FIM motor (standardized coefficient, β std = -0.112, p = 0.007) and showed a trend level association with year-1 FIM cognition (β std = -0.070, p = 0.079). Individuals with year-1 PTE were less likely to drive independently at year 1 (β std = -0.148, p < 0.001). In addition, FIM motor (β std = 0.323, p < 0.001), FIM cognition (β std = 0.181, p = 0.012), and anxiety (β std = -0.135, p = 0.024) influenced driving status. FIM cognition was associated with year-1 depression (β std = 0.386, p < 0.001) and year-1 anxiety (β std = 0.396, p < 0.001), whereas year-1 FIM motor (β std = 0.186, p = 0.003), depression (β std = -0.322, p = 0.011), and driving status (β std = 0.233, p < 0.001) directly affected year-2 objective life participation metrics. Moreover, year-1 depression (β std = -0.382, p = 0.001) and year-2 participation (β std = 0.160, p < 0.001) had direct effects on year-2 SWL. SWL was influenced indirectly by year-1 variables, including functional impairment, anxiety, and driving status-factors that impacted year-2 participation directly or indirectly, and consequently year-2 SWL, forming a complex relationship with year-1 PTE. A sensitivity analysis SEM showed that the number of MH disorders was associated with participation and SWL ( p < 0.001), and this combined MH variable was directly related to driving status ( p < 0.02). Developing PTE during year-1 after msTBI affects multiple aspects of life. PTE effects extend to motor and cognitive abilities, driving capabilities, and indirectly, to life participation and overall SWL. The implications underscore the crucial need for effective PTE management strategies during the first year post-TBI to minimize the adverse impact on factors influencing multidimensional year-2 participation and SWL outcomes. Addressing transportation barriers is warranted to enhance the well-being of those with PTE and msTBI, emphasizing a holistic approach. Further research is recommended for SEM validation studies, including testing causal inference pathways that might inform future prevention and treatment trials.

Background: Special Operations Forces (SOF) have become the solution to many of the United States military challenges due to their ability to conduct time sensitive, clandestine, and high-risk missions. Historically, SOF were assumed to be resilient to the psychological sequelae of war, including posttraumatic stress disorder (PTSD). However, the objective burden of PTSD in SOF, particularly after traumatic brain injury (TBI), remains unknown. This study compared average PTSD symptoms over time between SOF and Conventional Forces (CF) who had sustained a TBI., Methods: This prospective cohort study examined Servicemembers and Veterans admitted to one of five Veterans Affairs Polytrauma Rehabilitation Centers for TBI. Propensity score matching created matched samples of 205 SOF and 205 CF. The PTSD Checklist-Civilian version (PCL-C) measured PTSD symptoms at admission and 1, 2, 5, and 10 years post TBI., Results: In a longitudinal mixed-effects model of PTSD symptoms over time grouped by TBI severity, SOF and CF had similar severity and patterns of PTSD symptoms. SOF and CF with mild TBI had more PTSD symptoms across all time points compared to those with moderate and severe TBI., Conclusion: The evolution and severity of PTSD symptoms after TBI in SOF and CF were similar. While SOFs had higher resilience compared to CFs in previous work, SOFs are not impervious to trauma exposure and PTSD. Increasing awareness of PTSD prevalence and consequences is needed to serve SOF. Identifying those needing care and providing evidence-based PTSD treatments can have the downstream effects of reducing attrition from the service and maintaining military readiness., Competing Interests: The authors have no conflicts of interest to report. The funders had no say in the design of this study or the results. XT had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (2024.)

Objective: Although traumatic brain injury (TBI) and posttraumatic epilepsy (PTE) are common, there are no prospective models quantifying individual epilepsy risk after moderate-to-severe TBI (msTBI). We generated parsimonious prediction models to quantify individual epilepsy risk between acute inpatient rehabilitation for individuals 2 years after msTBI., Methods: We used data from 6089 prospectively enrolled participants (≥16 years) in the TBI Model Systems National Database. Of these, 4126 individuals had complete seizure data collected over a 2-year period post-injury. We performed a case-complete analysis to generate multiple prediction models using least absolute shrinkage and selection operator logistic regression. Baseline predictors were used to assess 2-year seizure risk (Model 1). Then a 2-year seizure risk was assessed excluding the acute care variables (Model 2). In addition, we generated prognostic models predicting new/recurrent seizures during Year 2 post-msTBI (Model 3) and predicting new seizures only during Year 2 (Model 4). We assessed model sensitivity when keeping specificity ≥.60, area under the receiver-operating characteristic curve (AUROC), and AUROC model performance through 5-fold cross-validation (CV)., Results: Model 1 (73.8% men, 44.1 ± 19.7 years, 76.1% moderate TBI) had a model sensitivity = 76.00% and average AUROC = .73 ± .02 in 5-fold CV. Model 2 had a model sensitivity = 72.16% and average AUROC = .70 ± .02 in 5-fold CV. Model 3 had a sensitivity = 86.63% and average AUROC = .84 ± .03 in 5-fold CV. Model 4 had a sensitivity = 73.68% and average AUROC = .67 ± .03 in 5-fold CV. Cranial surgeries, acute care seizures, intracranial fragments, and traumatic hemorrhages were consistent predictors across all models. Demographic and mental health variables contributed to some models. Simulated, clinical examples model individual PTE predictions., Significance: Using information available, acute-care, and year-1 post-injury data, parsimonious quantitative epilepsy prediction models following msTBI may facilitate timely evidence-based PTE prognostication within a 2-year period. We developed interactive web-based tools for testing prediction model external validity among independent cohorts. Individualized PTE risk may inform clinical trial development/design and clinical decision support tools for this population., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI)., Setting: Community., Participants: Participants ( n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury., Design: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury)., Main Measures: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control)., Results: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and FIM Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity., Conclusions: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine risk factors associated with homeboundness 1-year after traumatic brain injury (TBI) and to explore associations between homebound status and risk of future mortality and nursing home entry., Design: Secondary analysis of a longitudinal prospective cohort study., Setting: TBI Model Systems centers., Participants: Community-dwelling TBI Model Systems participants (n=6595) who sustained moderate-to-severe TBI between 2006 and 2016, and resided in a private residence 1-year postinjury., Interventions: Not applicable., Main Outcome Measures: Homebound status (leaving home ≤1-2d per week), 5-year mortality, and 2- or 5-year nursing home entry., Results: In our sample, 14.2% of individuals were homebound 1-year postinjury, including 2% who never left home. Older age, having less than a bachelor's degree, Medicaid insurance, living in the Northeast or Midwest, dependence on others or special services for transportation, unemployment or retirement, and needing assistance for locomotion, bladder management, and social interactions at 1-year postinjury were associated with being homebound. After adjustment for potential confounders and an inverse probability weight for nonrandom attrition bias, being homebound was associated with a 1.69-times (95% confidence interval, 1.35-2.11) greater risk of 5-year mortality, and a nonsignificant but trending association with nursing home entry by 5 years postinjury (RR=1.90; 95% confidence interval, 0.94-3.87). Associations between homeboundness and mortality were consistent by age subgroup (±65y)., Conclusions: The negative long-term health outcomes among persons with TBI who rarely leave home warrants the need to re-evaluate home discharge as unequivocally positive. The identified risk factors for homebound status, and its associated negative long-term outcomes, should be considered when preparing patients and their families for discharge from acute and postacute rehabilitation care settings. Addressing modifiable risk factors for homeboundness, such as accessible public transportation options and home care to address mobility, could be targets for individual referrals and policy intervention., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine, in persons with traumatic brain injury (TBI), the association between cognitive change after inpatient rehabilitation discharge and 1-year participation and life satisfaction outcomes., Design: Secondary analysis of prospectively collected TBI Model Systems (TBIMS) data., Setting: Inpatient rehabilitation and community., Participants: 499 individuals with TBI requiring inpatient rehabilitation who completed the Brief Test of Adult Cognition by Telephone (BTACT) at inpatient rehabilitation discharge (ie, baseline) and 1-year postinjury., Main Outcome Measures: Participation Assessment with Recombined Tools-Objective (PART-O) and Satisfaction with Life Scale (SWLS)., Results: Of 2,840 TBIMS participants with baseline BTACT, 499 met inclusion criteria (mean [standard deviation] age = 45 [19] years; 72% male). Change in BTACT executive function (EF) was not associated with 1-year participation (PART-O; β = 0.087, 95% CI [-0.004, 0.178], P = .061) when it was the sole model predictor. Change in BTACT episodic memory (EM) was associated with 1-year participation (β = 0.096, [0.007, 0.184], P = .035), but not after adjusting for demographic, clinical, and functional status covariates (β = 0.067, 95% CI [-0.010, 0.145], P = .089). Change in BTACT EF was not associated with life satisfaction total scores (SWLS) when it was the sole model predictor (β = 0.091, 95% CI [-0.001, 0.182], P = .0503). Change in BTACT EM was associated with 1-year life satisfaction before (β = 0.114, 95% CI [0.025, 0.202], P = .012) and after adjusting for covariates (β = 0.103, [0.014, 0.191], P = .023). In secondary analyses, change in BTACT EF was associated with PART-O Social Relations and Out and About subdomains before (Social Relations: β = 0.127, 95% CI [0.036, 0.217], P = .006; Out and About: β = 0.141, 95% CI [0.051, 0.232], P = .002) and after (Social Relations: β = 0.168, 95% CI [0.072, 0.265], P < .002; Out and About: β = 0.156, 95% CI [0.061, 0.252], P < .002) adjusting for functional status and further adjusting for covariates (Social Relations: β = 0.127, 95% CI [0.040, 0.214], P = .004; Out and About: β = 0.136, 95% CI [0.043, 0.229], P = .004). However, only the models adjusting for functional status remained significant after multiple comparison correction (ie, Bonferroni-adjusted alpha level = 0.002)., Conclusion: EF gains during the first year after TBI were related to 1-year social and community participation. Gains in EM were associated with 1-year life satisfaction. These results highlight the potential benefit of cognitive rehabilitation after inpatient rehabilitation discharge and the need for interventions targeting specific cognitive functions that may contribute to participation and life satisfaction after TBI., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 (β = 5.05; 95% CI, 1.59-8.50) and anxiety (β = 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., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 ( β  = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score ( β  = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors ( β  = - 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., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI)., Setting: Community., Participants: People enrolled in the TBI Model Systems National Database (TBIMS NDB)., Design: Secondary analysis of a longitudinal cohort study., Main Measures: The TBIMS-NSDI was calculated at the census tract level for the United States population based on a principal components analysis of eight census tract-level variables from the American Community Survey. Individual socioeconomic characteristics from the TBIMS NDB were personal household income, education (years), and unemployment status. Neighborhood:Individual NSDI residuals represent the difference between predicted neighborhood disadvantage based on individual socioeconomic characteristics versus observed neighborhood disadvantage based on the TBIMS-NSDI., Results: A single principal component was found to encompass the eight socioeconomic neighborhood-level variables. It was normally distributed across follow-up years 2, 5, and 10 post-injury in the TBIMS NDB. In all years, the TBIMS-NDSI was significantly associated with individual-level measures of household income and education but not unemployment status. Males, persons of Black and Hispanic background, Medicaid recipients, persons with TBI caused by violence, and those living in urban areas, as well as in the Northeast or Southern regions of the United States, were more likely to have greater neighborhood disadvantage than predicted based on their individual socioeconomic characteristics., Conclusions: The TBIMS-NSDI provides a neighborhood-level indicator of socioeconomic disadvantage, an important social determinant of outcomes from TBI. The Neighborhood:Individual NSDI residual adds another dimension to the TBIMS-NSDI by summarizing how a person's socioeconomic status aligns with their neighborhood socioeconomics. Future studies should evaluate how both measures affect TBI recovery and life quality. Research studying neighborhood socioeconomic disadvantage may improve our understanding of how systemic adversity influences outcomes after TBI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose/objective: To examine the association of changes in homebound status (i.e., never/rarely leaving the home) with life satisfaction in the first 10 years after traumatic brain injury (TBI)., Research Method/design: We analyzed data from 2,294 individuals with moderate-to-severe TBI from the TBI Model Systems National Database using a longitudinal multilevel model with time-varying predictors to account for within-person changes over time as well as between-person differences. We measured homebound status (defined as leaving the home ≤ 2 days/week) and life satisfaction (defined as the total score on the Satisfaction With Life Scale) at 1, 2, 5, and 10 years post-TBI. We adjusted the models for demographic and injury-related covariates and used inverse probability weighting to account for selection bias., Results: Forty-five (2%) individuals were homebound at all follow-up visits, 523 (22.8%) were homebound at least one follow-up visit, and 1,726 (75.2%) were never homebound. Individuals with TBI who were consistently homebound had > 1 SD lower life satisfaction compared to those who were never homebound, β = -8.07, 95% confidence interval (CI) = [-9.39, -6.76], p < .001. Individuals who became homebound experienced a significant, but modest, decline in life satisfaction (β = -2.13, 95% CI = [-2.66, -1.61], p < .001)., Conclusions/implications: Our results indicate that being homebound and becoming homebound are associated with decreased life satisfaction. Homeboundness is a potentially modifiable target to improve life satisfaction, and elucidation of contributing factors to homebound status will help develop interventions to ameliorate post-TBI homeboundness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose. To characterize societal participation profiles after moderate-severe traumatic brain injury (TBI) along objective (Frequency) and subjective (Satisfaction, Importance, Enfranchisement) dimensions. Materials and Methods. We conducted secondary analyses of a TBI Model Systems sub-study ( N  = 408). Multiaxial assessment of participation included the Participation Assessment with Recombined Tools-Objective and -Subjective questionnaires (Participation Frequency and Importance/Satisfaction, respectively) and the Enfranchisement Scale. Participants provided responses via telephone interview 1-15 years post-injury. Multidimensional participation profiles (classes) were extracted using latent profile analysis. Results. A 4-class solution was identified as providing maximal statistical separation between profiles and being clinically meaningful based on profile demographic features. One profile group (48.5% of the sample) exhibited the "best" participation profile (High Frequency, Satisfaction, Importance, and Enfranchisement) and was also the most advantaged according to socioeconomic indicators. Other profile groups showed appreciable heterogeneity across participation dimensions. Age, race/ethnicity, education level, ability to drive, and urbanicity were features that varied between profiles. Conclusions. Societal participation is a critical, but inherently complex, TBI outcome that may not be adequately captured by a single index. Our data underscore the importance of a multidimensional approach to participation assessment and interpretation using profiles. The use of participation profiles may promote precision health interventions for community integration.Implications for RehabilitationOur study found unidimensional measures of societal participation in traumatic brain injury (TBI) populations that focus exclusively on frequency indicators may be overly simplistic and miss key subjective components of participationTaking a multidimensional perspective, we documented four meaningfully distinct participation subgroups (including both objective and subjective dimensions of societal participation) within the TBI rehabilitation populationMultidimensional profiles of participation may be used to group individuals with TBI into target groups for intervention (e.g., deeper goal assessment for individuals who do not rate standard participation activities as important, but also do not participate and do not feel enfranchised).

Background: The purpose of this study is to compare the prevalence of self-reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity-matched control cohort., Methods and Results: A cross-sectional study described self-reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed-effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity-score matching based on age, sex, race, ethnicity, body mass index, education level, and smoking status. The final sample was 4690 matched pairs. Individuals with TBI were more likely to report hypertension (odds ratio [OR], 1.18 [95% CI, 1.08-1.28]) and stroke (OR, 1.70 [95% CI, 1.56-1.98]) but less likely to report CHF (OR, 0.81 [95% CI, 0.67-0.99]) or MI (OR, 0.66 [95% CI, 0.55-0.79]). There was no difference in rate of CHF or MI for those ≤50 years old; however, rates of CHF and MI were lower in the TBI group for individuals >50 years old. Over 65% of individuals who died before the first follow-up interview at 1 year post-TBI were >50 years old, and those >50 years old were more likely to die of heart disease than those ≤50 years old (17.6% versus 8.6%)., Conclusions: Individuals with moderate to severe TBI had an increased rate of self-reported hypertension and stroke but lower rate of MI and CHF than uninjured adults, which may be due to survival bias.

We examined whether females with a history of traumatic brain injury (TBI) and intimate partner violence (IPV) have greater exposure to lifetime trauma relative to females with TBI but no IPV history. Further, we assessed the effects of lifetime trauma on psychological outcomes after TBI. Female participants ( n  = 70; age M [standard deviation-SD] = 50.5 [15.2] years) with TBI (time since injury median [interquartile range -IQR] = 10.2 [5.3-17.8] years) completed a structured assessment of lifetime history of TBI, including an IPV module to query head injuries from physical violence by an intimate partner. We characterized lifetime trauma exposure with the Adverse Childhood Experiences (ACEs) questionnaire and Survey of Exposure to Community Violence (CV). We evaluated psychological functioning with self-report questionnaires of post-traumatic stress disorder (PTSD), depression, and anxiety symptoms. Compared with those with no IPV history ( n  = 51), participants reporting IPV-related head injuries ( n  = 19; 27.1%) reported more ACEs (M[SD] IPV: 4.5[2.9]; No IPV: 1.6[1.8], p  < 0.001, d  = 1.08) and greater CV (IPV: 17.5[8.4]; No IPV: 7.6[6.1], p  < .0001, d  = 1.26). Within the full sample, ACEs (β = 0.21, 95% confidence interval [CI] = 0.04-0.39) and CV (β = 0.07, 95% CI = 0.01-0.13) predicted worse PTSD symptoms, while IPV alone did not. Exposure to all three sources of trauma (ACEs, CV, and IPV) was associated with worse PTSD symptoms relative to fewer traumas. The results highlight the scope of traumatic exposures among TBI survivors and the importance of considering IPV and other lifetime trauma exposure in assessing and managing TBI. Trauma-informed interventions that are modified for TBI-related impairment may offer improved outcomes in managing psychological symptoms.

Objective: The aim of this study was to look for feasibility of non-contrast CT (NCCT) in detecting peripheral zone prostate cancer (PCa)., Methods: A retrospective analysis included 50 biopsy-proven PCa patients between April 2019 and March 2022 who underwent staging whole body prostate-specific membrane antigen (PSMA)/CT prior to treatment. The control subjects were 50 randomly selected adult male patients who underwent PET/CT for non-prostate malignancy during the same time period. Two readers independently calculated the Hounsfield unit (HU) of normal peripheral zone, central zone, and corresponding PSMA avid focus in cases., Results: No significant difference was seen in the mean HU value of normal peripheral zone between cases and controls. Significant difference in the mean HU was seen between the PSMA avid focus in cases (40.1 ± 6.2) and normal peripheral zone of cases (28.2 ± 7.0) and controls (27.7 ± 5.8). No significant difference was found between the mean HU values of high-grade PCa and non-high-grade PCa. Receiver operating characteristic (ROC) curve analysis revealed a mean HU cut-off of ≥35 for detecting PCa with a sensitivity and specificity of 86% and 90%, respectively, between cases and controls (AUC 0.88)., Conclusion: Detection of clinically significant PCa is possible on routinely performed NCCT scans. Radiologists should routinely look for and convey these findings to facilitate further work-up and early detection of PCa., Advances in Knowledge: Our study adds to the knowledge that NCCT scans performed for unrelated indications can serve as a screening tool for clinically significant PCa., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: There is evidence that health care utilization increases after incident dementia, particularly after dementia diagnosis and toward the end of life; however, less is known about utilization in the years before dementia identification., Methods: In this retrospective cohort study we obtained data on n = 5547 beneficiaries from the Health and Retirement Study (HRS)-Medicare linked sample (n = 1241 with and n = 4306 without dementia) to compare longitudinal trends in health care costs and utilization in the 6 years preceding dementia identification relative to a confounder-balanced reference group without dementia., Results: We found that persons with dementia had a greater prevalence of outpatient emergency department (ED), inpatient hospital, skilled nursing, and home health use, and total health care costs in the years preceding dementia identification compared to their similar counterparts without dementia across a comparable timespan in later life., Conclusions: This study provides evidence to suggest greater healthcare burden may exist well before clinical manifestation and identification of dementia., Highlights: Several studies have documented the tremendous healthcare-related costs of living with dementia, particularly toward the end of life. Dementia is a progressive neurodegenerative disease, which, for some, includes a prolonged pre-clinical phase. However, health services research to date has seldom considered the time before incident dementia. This study documents that health care utilization and costs are significantly elevated in the years before incident dementia relative to a demographically-similar comparison group without dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples., Methods: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately., Results: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010)., Discussion: In NHW adults, APOE ε2 may protect men but not women against cognitive decline., Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2-positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls. These results were confirmed and extended in the K18-humanized angiotensin-converting enzyme 2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the USA), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila . Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology. IMPORTANCE Taken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2, it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease., Competing Interests: P.J.T. is on the scientific advisory boards for Pendulum, Seed, and SNIPRbiome; there is no direct overlap between the current study and these consulting duties. The other authors declare no competing interests.

For many years, experts have recognized the importance of studying traumatic brain injury (TBI) among active-duty service members and veterans. A majority of this research has been conducted in Veterans Administration (VA) or Department of Defense settings. However, far less is known about military personnel who seek their medical care outside these settings. Studies that have been conducted in civilian settings have either not enrolled active duty or veteran participants, or failed to measure military history, precluding study of TBI outcomes by military history. The purpose of the present study was to determine associations between military history and medical (prevalence of 25 comorbid health conditions), cognition (Brief Test of Adult Cognition by Telephone), and psychological health (Patient Health Questionnaire-9 [PHQ-9], Generalized Anxiety Disorder-7, suicidality [9th item from PHQ-9]) in the first 5 years after TBI. In this prospective study, we analyzed data from the TBI Model Systems National Database. Participants were 7797 individuals with TBI admitted to one of 21 civilian inpatient rehabilitation facilities from April 1, 2010, to November 19, 2020, and followed up to 5 years. We assessed the relationship between military history (any versus none, combat exposure, service era, and service duration) and TBI outcomes. We found specific medical conditions were significantly more prevalent 1 year post-TBI among individuals who had a history of combat deployment (lung disorders, post-traumatic stress disorder [PTSD], and sleep disorder), served in post-draft era (chronic pain, liver disease, arthritis), and served >4 years (high cholesterol, PTSD, sleep disorder). Individuals with military history without combat deployment had modestly more favorable cognition and psychological health in the first 5 years post-injury relative to those without military history. Our data suggest that individuals with TBI with military history are heterogeneous, with some favorable and other deleterious health outcomes, relative to their non-military counterparts, which may be driven by characteristics of service, including combat exposure and era of service.

Introduction: The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies., Methods: We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aβ), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis)., Results: The detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non-AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men., Discussion: The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia., Highlights: Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late-life cognition are mediated by AD neuropathology. The estimated mediated effects of most measures of AD neuropathology were similar. Non-Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD. Non-AD vascular pathologies did not mediate the effect of the APOE genotype on cognition. The protective effect of APOE ε2 on cognition was stronger in women., (© 2022 the Alzheimer's Association.)

Introduction: As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear., Materials and Methods: We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC., Results: Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): -0.042 (-0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer's disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness., Conclusions: Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Precise estimation of genome size (GS) is vital for various genomic studies, such as deciding genome sequencing depth, genome assembly, biodiversity documentation, evolution, genetic disorders studies, duplication events etc. Animal Genome Size Database provides GS of over 2050 fish species, which ranges from 0.35 pg in pufferfish (Tetraodon nigroviridis) to 132.83 pg in marbled lungfish (Protopterus aethiopicus). The GS of majority of the fishes inhabiting waters of Indian subcontinent are still missing. In present study, we estimated GS of 51 freshwater teleost (31 commercially important, 7 vulnerable and 13 ornamental species) that ranged from 0.58 pg in banded gourami (Trichogaster fasciata) to 1.92 pg in scribbled goby (Awaous grammepomus). Substantial variation in GS was observed within the same fish orders (0.64-1.45 pg in cypriniformes, 0.70-1.41 pg in siluriformes and 0.58-1.92 pg in perciformes). We examined the relationship between the GS, chromosome number and body length across all the fishes. Body length was found to be associated with GS, whereas no relationship was noticed between the GS and the chromosome number. The analysis using ancestral information revealed haploid chromosome number 25, 27 and 24 for the most recent common ancestor of cypriniformes, siluriformes and perciformes, respectively. The study led to generation of new records on GS of 43 fish species and revalidated records for 8 species. The finding is valuable resource for further research in the areas of fish genomics, molecular ecology and evolutionary conservation genetics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 (β = -0.18, P < .01) and anxiety symptoms and the BTACT Composite score (β = -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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Persons with military involvement may be more likely to have Parkinson's disease (PD) risk factors. As PD is rare, case finding remains a challenge, contributing to our limited understanding of PD risk factors. Here, we explore the validity of case-finding strategies and whether military employment is associated with PD., Materials and Methods: We identified Adult Changes in Thought (ACT) study participants reporting military employment as their longest or second longest occupation. We used self-report and prescription fills to identify PD cases and validated this case-finding approach against medical record review., Results: At enrollment, 6% of 5,125 eligible participants had military employment and 1.8% had prevalent PD; an additional 3.5% developed PD over follow-up (mean: 8.3 years). Sensitivity of our case-finding approach was higher for incident (80%) than prevalent cases (54%). Specificity was high (>97%) for both. Military employment was not associated with prevalent PD. Among nonsmokers, point estimates suggested an increased risk of incident PD with military employment, but the result was non-significant and based on a small number of cases., Conclusions: Self-report and prescription medications can accurately identify incident PD cases relative to the reference method of medical record review. We found no association between military employment and PD.

Aim: This pilot study's aim was to determine the feasibility of examining the effects of an environmental variable (i.e., tree canopy coverage) on mental health after sustaining a brain injury., Methods: A secondary data analysis was conducted leveraging existing information on mental health after moderate to severe traumatic brain injury (TBI) from the TBI Model System. Mental health was measured using PHQ-9 (depression) and GAD-7 (anxiety) scores. The data were compared with data on tree canopy coverage in the state of Texas that was obtained from the Multi-Resolution Land Characteristics (MRLC) Consortium using GIS analysis. Tree canopy coverage as an indicator of neighborhood socioeconomic status was also examined using the Neighborhood SES Index., Results: Tree canopy coverage had weak and non-significant correlations with anxiety and depression scores, as well as neighborhood socioeconomic status. Data analysis was limited by small sample size. However, there is a higher percentage (18.8%) of participants who reported moderate to severe depression symptoms in areas with less than 30% tree canopy coverage, compared with 6.6% of participants who endorsed moderate to severe depression symptoms and live in areas with more than 30% tree canopy coverage (there was no difference in anxiety scores)., Conclusion: Our work confirms the feasibility of measuring the effects of tree canopy coverage on mental health after brain injury and warrants further investigation into examining tree canopy coverage and depression after TBI. Future work will include nationwide analyses to potentially detect significant relationships, as well as examine differences in geographic location., (© 2023 The Authors. Published by Elsevier Inc.)

Background: Prior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization., Objective: To investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort., Methods: Self-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research. Self-report data were supplemented with medical record abstraction, and, for 244 people, structured interviews on lifetime head trauma. Neuropathology outcomes included Braak stage, CERAD neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral/cortical atrophy. Exposures were TBI with or without LOC. Modified Poisson regressions adjusting for age, sex, education, and APOE ɛ4 genotype were weighted back to the full cohort of 5,546 participants., Results: TBI with LOC was associated with the presence of cerebral cortical atrophy (Relative Risk 1.22, 95% CI 1.02, 1.42). None of the other outcomes was associated with TBI with or without LOC., Conclusion: TBI with LOC was associated with increased risk of cerebral cortical atrophy. Despite our enhanced TBI ascertainment, we found no association with the Alzheimer's disease-related neuropathologic outcomes among people who survived to at least age 65 without dementia. This suggests the pathophysiological processes underlying post-traumatic neurodegeneration are distinct from the hallmark pathologies of Alzheimer's disease.

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-β and tau. Proportion of morphologically activated microglia was determined via immunohistochemistry (HLA-DP-DQ-DR) and morphological staging (stage I, II or III). Amyloid-β 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-β to tau relationship in the whole sample and stratified by sex (amyloid-β → microglial activation → tau). Alternative models tested the role of microglia activation as the precipitating event (microglial activation → amyloid-β → tau). Microglial activation significantly mediated 33% [95% confidence interval (CI) 10-67] of the relationship between amyloid-β 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-β 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-β 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-β 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-β 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Homebound persons living with dementia may have increased difficulty accessing needed care in the community. This study identifies factors associated with becoming homebound among a national sample of Medicare beneficiaries with newly identified dementia., Design: Prospective cohort analysis., Setting and Participants: We used the National Health and Aging Trends Study (NHATS) 2011-2018 to identify community-dwelling older adults at the time of a new dementia diagnosis (n = 939). Dementia status was determined based on cognitive testing and self and proxy reporting., Methods: We compared characteristics of homebound (ie, those who never or rarely left home) and non-homebound participants at the time of dementia identification. Among non-homebound participants, we used a Fine-Gray subdistribution hazard model to identify factors associated with becoming homebound over follow-up (median follow-up 4 years), accounting for competing risks of death and moving to a nursing home., Results: 20% of individuals with newly identified dementia were homebound and this group was more functionally impaired, medically complex, and socioeconomically disadvantaged as compared to the non-homebound. Over time, depression [subhazard ratio (SHR) 2.19, 95% CI 1.36, 3.54], living in an assisted living facility (SHR 2.60, 95% CI 1.35, 4.97), and Hispanic ethnicity (SHR 1.91, 95% CI 1.05, 3.47) were associated with becoming homebound., Conclusions and Implications: Most adults are not homebound at the time of dementia diagnosis. Identifying and addressing modifiable factors like depression may slow progression to homebound status and enable persons living with dementia to access needed care in the community. In order to accommodate diverse individual and family preferences for long-term care, robust systems of home-based clinical and long-term care are necessary for those who do become homebound., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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 β-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 β-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 β-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 β-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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To discern whether there is evidence that individuals who sustained a traumatic brain injury (TBI) had the greater odds of preexisting health conditions and/or poorer health behaviors than matched controls without TBI., Setting: Brain Injury Inpatient Rehabilitation Unit at Mount Sinai Hospital. Midlife in the United States (MIDUS) control data were collected via random-digit-dialing phone survey., Participants: TBI cases were enrolled in the TBI Health Study and met at least 1 of the following 4 injury severity criteria: abnormal computed tomography scan; Glasgow Coma Scale score between 3 and 12; loss of consciousness greater than 30 minutes; or post-TBI amnesia longer than 24 hours. Sixty-two TBI cases and 171 matched MIDUS controls were included in the analyses; controls were excluded if they reported having a history of head injury., Design: Matched case-control study., Main Measures: Self-reported measures of depression symptoms, chronic pain, health status, alcohol use, smoking status, abuse of controlled substances, physical activity, physical health composite score, and behavioral health composite score., Results: Pre-index injury depression was nearly 4 times higher in TBI cases than in matched controls (OR= 3.98, 95% CI, 1.71-9.27; P = .001). We found no significant differences in the odds of self-reporting 3 or more medical health conditions in year prior to index injury (OR = 1.52; 95% CI, 0.82-2.81; P = .183) or reporting more risky health behaviors (OR = 1.48; 95% CI; 0.75-2.91; P = .254]) in individuals with TBI than in controls., Conclusion: These preliminary findings suggest that the odds of depression in the year prior to index injury far exceed those reported in matched controls. Further study in larger samples is required to better understand the relative odds of prior health problems in those who sustain a TBI, with a goal of elucidating the implications of preinjury health on post-TBI disease burden., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the impact of COVID-19 pandemic exposure on changes in alcohol use and mood from years 1 to 2 after traumatic brain injury (TBI)., Methods: We used a difference-in-difference (DiD) study design to analyze data from 1,059 individuals with moderate-to-severe TBI enrolled in the TBI Model Systems (TBIMS) National Database. We defined COVID-19 pandemic exposure as participants who received their year 1 post-injury interviews prior to January 1, 2020, and their year 2 interview between April 1, 2020 and January 15, 2021. Pandemic-unexposed participants had both year 1 and 2 follow-up interviews before January 1, 2020. We measured current alcohol use as any past month alcohol use, average number of drinks per drinking occasion, and past month binge drinking. We measured depression symptoms using Patient Health Questionnaire-9, and anxiety symptoms using the Generalized Anxiety Disorder-7., Results: We found persons with TBI exposed to the pandemic had greater increases in the average number of drinks per occasion from year 1 to 2 post-injury compared to pandemic-unexposed individuals (β = 0.36, 95% CI: 0.16, 0.57, p = 0.001), with males, adults <65 years old, and Black and Hispanic subgroups showing the greatest increases in consumption. Though average consumption was elevated, changes in rates of any alcohol use or binge drinking by pandemic exposure were not observed. Overall, there were no significant changes in depressive and anxiety symptoms over time between pandemic exposed and unexposed groups; however, pandemic-exposed Hispanics with TBI reported significant increases in anxiety symptoms from year-1 to year-2 post-injury compared to pandemic-unexposed Hispanics (β = 2.35, 95% CI: 0.25, 4.47, p = 0.028)., Conclusion: Among persons living with TBI, those exposed to the pandemic had significant increases in average alcohol consumption. Pandemic-exposed Hispanics with TBI had large elevations in anxiety symptoms, perhaps reflecting health inequities exacerbated by the pandemic, and suggesting a need for targeted monitoring of psychosocial distress., Competing Interests: Dr. Adams consults for TIAG, in support of the National Intrepid Center of Excellence (NICOoE) at Walter Reed National Medical Center. This does not alter our adherence to PlosOne policies on sharing data and materials.

Background: Older adults comprise an increasingly large proportion of patients with traumatic brain injury (TBI) receiving care in inpatient rehabilitation facilities (IRF). However, high rates of comorbidities and evidence of declining preinjury health among older adults who sustain TBI raise questions about their ability to benefit from IRF care., Objectives: To describe the proportion of older adults with TBI who exhibited minimal detectable change (MDC) and a minimally clinically important difference (MCID) in motor function from IRF admission to discharge; and to identify characteristics associated with clinically meaningful improvement in motor function and better discharge functional status., Design: This retrospective cohort study used Medicare administrative data probabilistically linked to the National Trauma Data Bank to estimate the proportion of patients whose motor function improved during inpatient rehabilitation and identify factors associated with meaningful improvement in motor function and motor function at discharge., Setting: Inpatient rehabilitation facilities in the United States., Patients: Fee-for-service Medicare beneficiaries with TBI., Main Outcome Measures: Minimal Detectable Change (MDC) and Minimally Clinically Important Difference (MCID) in the Functional Independence Measure motor (FIM-M) score from admission to discharge, and FIM-M score at IRF discharge., Results: From IRF admission to discharge 84% of patients achieved the MDC threshold, and 68% of patients achieved the MCID threshold for FIM-M scores. Factors associated with a higher probability of achieving the MCID for FIM-M scores included better admission motor and cognitive function, lower comorbidity burden, and a length of stay longer than 10 days but only among individuals with lower admission motor function. Older age was associated with a lower FIM-M discharge score, but not the probability of achieving the MCID in FIM-M score., Conclusion: Older adults with TBI have the potential to improve their motor function with IRF care. Baseline functional status and comorbidity burden, rather than acute injury severity, should be used to guide care planning., (© 2021 American Academy of Physical Medicine and Rehabilitation.)

Objectives: To evaluate associations between traumatic brain injury (TBI) and presence of health conditions, and to compare associations of health and cognition between TBI cases and controls., Methods: This matched case-control study used data from the TBI Model Systems National Database (TBI cases) and Midlife in the United States II and Refresher studies (controls).  248 TBI cases were age-, sex-, race-, and education-matched without replacement to three controls. Cases and controls were compared on prevalence of 18 self-reported conditions, self-rated health, composite scores from the Brief Test of Adult Cognition by Telephone., Results: The following conditions were significantly more prevalent among TBI cases versus controls: anxiety/depression (OR = 3.12, 95% CI: 2.20, 4.43, p < .001), chronic sleeping problems (OR = 2.76, 95% CI: 1.86, 4.10, p < .001), headache/migraine (OR = 2.61, 95% CI: 1.50, 4.54, p = .0007), and stroke (OR = 6.42, 95% CI: 2.93, 14.10, p < .001). The relationship between self-rated health and cognition significantly varied by TBI ( p interaction  = 0.002)., Conclusion: Individuals with TBI have greater odds of selected neurobehavioral conditions compared to their demographically similar uninjured peers. Among persons with TBI there was a stronger association between poorer self-rated health and cognition than controls. TBI is increasingly conceptualized as a chronic disease; current findings suggest post-TBI health management requires cognitive supports.

Several studies have characterized comorbidities among individuals with traumatic brain injury (TBI); however, there are few validated TBI comorbidity indices. Widely used indices (e.g., Elixhauser Comorbidity Index [ECI]) were developed in other patient populations and anchor to mortality or healthcare utilization, not functioning, and notably exclude conditions known to co-occur with TBI. The objectives of this study were to develop and validate a functionally relevant TBI comorbidity index (Fx-TBI-CI) and to compare prognostication of the Fx-TBI-CI with the ECI . We used data from the eRehabData database to divide the sample randomly into a training sample (N = 21,292) and an internal validation sample (N = 9166). We used data from the TBI Model Systems National Database as an external validation sample (N = 1925). We used least absolute shrinkage and selection operator (LASSO) regression to narrow the list of functionally relevant conditions from 39 to 12. In internal validation, the Fx-TBI-CI explained 14.1% incremental variance over an age and sex model predicting the Functional Independence Measure (FIM) Motor subscale at inpatient rehabilitation discharge, compared with 2.4% explained by the ECI. In external validation, the Fx-TBI-CI explained 4.9% incremental variance over age and sex and 3.8% over age, sex, and Glasgow Coma Scale score,compared with 2.1% and 1.6% incremental variance, respectively, explained by the ECI. An unweighted Sum Condition Score including the same conditions as the Fx-TBI-CI conferred similar prognostication. Although the Fx-TBI-CI had only modest incremental variance over demographics and injury severity in predicting functioning in external validation, the Fx-TBI-CI outperformed the ECI in predicting post-TBI function.

Tuberculosis is ancient disease known to mankind. Diagnosis and management of spinal tuberculosis has immensely improved in last few decades. Imaging, particularly MRI, plays important role in diagnosis of spinal tuberculosis and its complications. Four common imaging patterns of spinal tuberculosis include paradiscal type, central type, Anterior subligamentous type, and posterior type. Imaging also plays important role in differentiation of spinal tuberculosis from its mimics, particularly pyogenic spondylitis, and metastasis. Radiological interventions, such as CT guided vertebral biopsy, and percutaneous drainage of cold abscess, are commonly used in management of spinal tuberculosis. Monitoring of therapeutic response is often based on clinical evaluation and imaging. MRI is most common imaging modality used. Signs of healing include bony ankylosis, resolution of marrow edema, decrease in contrast enhancement, and fatty change with in bone marrow. PET CT is recently evaluated for response assessment with promising results. This review summarizes pathophysiology, clinical presentation, imaging features, radiological interventions, and response assessment in spinal tuberculosis., Competing Interests: None., (© 2021.)

Background: Cognitive impairments commonly occur after traumatic brain injury (TBI) and affect daily functioning. Cortisol levels, which are elevated during acute hospitalization for most individuals after severe TBI, can influence cognition, but this association has not been studied previously in TBI., Objective: We hypothesized that serum and cerebral spinal fluid (CSF) cortisol trajectories over days 0-5 post-injury are associated with cognition 6-month post-injury., Methods: We examined 94 participants with severe TBI, collected acute serum and/or CSF samples over days 0-5 post-injury, and compared cortisol levels to those in 17 healthy controls. N = 88 participants had serum, and n = 84 had CSF samples available for cortisol measurement and had neuropsychological testing 6 months post-injury. Group based trajectory analysis (TRAJ) was used to generate temporal serum and CSF cortisol profiles which were examined for associations with neuropsychological performance. We used linear regression to examine relationships between cortisol TRAJ groups and both overall and domain-specific cognition., Results: TRAJ analysis identified a high group and a decliner group for serum and a high group and low group for CSF cortisol. Multivariable analysis showed serum cortisol TRAJ group was associated with overall cognitive composites scores ( P = .024) and with executive function ( P = .039) and verbal fluency ( P = .029) domain scores. CSF cortisol TRAJ group was associated with overall cognitive composite scores ( P = .021) and domain scores for executive function ( P = .041), verbal fluency ( P = .031), and attention ( P = .034)., Conclusions: High acute cortisol trajectories are associated with poorer cognition 6 months post-TBI.

Megalocytivirus cause diseases that have serious economic impacts on aquaculture, mainly in East and South-East Asia. Five primary genotypes are known: infectious spleen and kidney necrosis virus (ISKNV), red sea bream iridovirus (RSIV), turbot reddish body iridovirus (TRBIV), threespine stickleback iridovirus (TSIV) and scale drop disease virus (SDDV). ISKNV-mediated infectious spleen and kidney necrosis disease (ISKND) is a major viral disease in both freshwater and marine fish species. In this study, we report the isolation of ISKNV from diseased giant gourami, Osphronemus goramy, in India. Transmission electron microscopy of ultrathin sections of kidney and spleen revealed the presence of numerous polygonal naked viral particles having an outer nucleocapsid layer within the cytoplasm of enlarged cells (115-125 nm). Molecular and phylogenetic analyses confirmed the presence of ISKNV and the major capsid protein (MCP) (1,362 bp) gene in the infected fish had a high similarity to the other ISKNV-I isolates. Moreover, ISKNV was propagated in the Astronotus ocellatus fin (AOF) cell line and further confirmed genotypically. A high mortality rate (60%) was observed in gourami fish injected with ISKNV-positive tissue homogenate through challenge studies. Considering the lethal nature of ISKNV, the present study spotlights the implementation of stringent biosecurity practices for the proper control of the disease in the country., (© 2021 John Wiley & Sons Ltd.)

Objective: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life., Design: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis., Setting: Community-based integrated health care delivery system., Participants: Participants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free., Interventions: Not applicable., Main Outcome Measures: ADL difficulties at baseline and accumulation during follow-up., Results: TBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses., Conclusions: Further investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted., (Copyright © 2021. Published by Elsevier Inc.)

Understanding the effects of age on longitudinal traumatic brain injury (TBI) outcomes requires attention to both chronic and evolving TBI effects and age-related changes in health and function. The present study examines the independent and interactive effects of aging and chronicity on functional outcomes after TBI. We leveraged a well-defined cohort of individuals who sustained a moderate/severe TBI and received acute inpatient rehabilitation at specialized centers with high follow up rate as part of their involvement in the TBI Model Systems longitudinal study. We selected individuals at one of two levels of TBI chronicity (either 2 or 10 years post-injury) and used an exact matching procedure to obtain balanced chronicity groups based on age and other characteristics ( N  = 1993). We found that both older age and greater injury chronicity were related to greater disability, reduced functional independence, and less community participation. There was a significant age by chronicity interaction, indicating that the adverse effects of greater time post-injury were most pronounced among survivors who were age 75 or older. The inflection point at roughly 75 years of age was corroborated by post hoc analyses, dividing the sample by age at 75 years and examining the interaction between age group and chronicity. These findings point to a need for provision of rehabilitation services in the chronic injury period, particularly for those who are over 75 years old. Future work should investigate the underlying mechanisms of this interaction towards the goal of developing interventions and models of care to promote healthy aging with TBI.