Neuropsychological Profiles of Deployment-Related Mild Traumatic Brain Injury: A LIMBIC-CENC Study.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date. METHODS: We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It is important to note that the profiles were determined independently of mTBI and probable PTSD status. After profile identification, we examined associations between demographic variables, mTBI characteristics, and PTSD symptoms with symptom profile membership. RESULTS: The analytic sample included 1,659 SMV (mean age 41.1 ± 10.0 years; 87% male); among them 29% (n = 480) had a history of non-deployment-related mTBI only, 14% (n = 239) had deployment-related mTBI only, 36% (n = 602) had both non-deployment and deployment-related mTBI, and 30% (n = 497) met criteria for probable PTSD. A 6-profile model had the best fit, with separation on all indicators (p < 0.001). The model revealed distinct neuropsychological profiles, representing a combination of 3 self-reported functioning patterns: high (HS), moderate (MS), and low (LS), and 2 cognitive performance patterns: high (HC) and low (LC). The profiles were (1) HS/HC: n=301, 18.1%; (2) HS/LC: n=294, 17.7%; (3) MS/HC: n=359, 21.6%; (4) MS/LC: n=316, 19.0%; (5) LS/HC: n=228, 13.7%; and (6) LS/LC: n=161, 9.7%. SMV with deployment-related mTBI tended to be grouped into lower functioning profiles and were more likely to meet criteria for probable PTSD. Conversely, SMV with no mTBI exposure or non-deployment-related mTBI were clustered in higher functioning profiles and had a lower likelihood of meeting criteria for probable PTSD. DISCUSSION: Findings suggest varied symptom and functional profiles in SMV, influenced by injury context and probable PTSD comorbidity. Despite diagnostic challenges, comprehensive assessment of functioning and cognition can detect subtle differences related to mTBI and PTSD, revealing distinct neuropsychological profiles. Prioritizing early treatment based on these profiles may improve prognostication and support efficient recovery.

More Than Skin Deep: Patient-Provider Racial and Ethnic Concordance and Discordance in Collegiate Athletics and Concussion Management.

CONTEXT: There is strong evidence that racial and ethnic disparities exist in multiple arenas of health and wellness. The causes of racial and ethnic differences in healthcare are multi- dimensional, one factor that may impact injury/illness communication, interactions, and outcomes is patient-provider racial and ethnic concordance. At present, it is unclear what role patient-provider racial and ethnic concordance and discordance plays in facilitating concussion care for collegiate athletes. OBJECTIVE: Investigate the presence of athlete-athletic trainer (AT) racial and ethnic concordance and discordance amongst diagnosed concussion cases, and examine if racial and ethnic concordance and discordance influences time (in days) until diagnosis, symptom resolution, or return-to-sport clinical milestones in collegiate athletes. DESIGN: Retrospective cohort study. SETTING: Collegiate athletics. PATIENTS OR OTHER PARTICIPANTS: A total of 694 concussion cases [38.6% (n=268) sustained by women, 61.4% (n=426) sustained by men] that occurred within the 2015-2016 through 2019- 2020 sport seasons at 9 institutions. MAIN OUTCOME MEASURE(S): The number of days from date of injury to diagnosis, symptom resolution, and return-to-sport; and from date of diagnosis to symptom resolution and return-to- sport. RESULTS: Overall, 68.4% (n=475) of concussion cases had patient-provider racial and ethnic concordance and 31.6% (n =219) were discordant. All concordant pairs included a White athlete and White AT. Time to diagnosis differed between the concordant and discordant groups (median[IQR]=1[0,2] versus 0[0,1], respectively) only in the model adjusted for sex, sport-type, and availability of an AT (OR[CI95]=1.46[1.07, 1.85]). There were no other group differences. CONCLUSIONS: One-third of concussion cases had athlete-AT racial and ethnic discordance. While this group was diagnosed with a concussion 1-day sooner than the concordant group, no differences were observed for any concussion recovery milestones. These findings suggest that patient-provider racial and ethnic concordance may play a minor role in concussion recognition or reporting, but not necessarily in the management and recovery thereafter.

Influence of sleep symptoms on recovery from concussion in collegiate athletes: a LIMBIC MATARS consortium investigation.

OBJECTIVE: Changes in sleep quality and quantity are commonly endorsed by individuals following a concussion. Limited data exists examining the role of sleep disturbances within 72 hours, and throughout recovery, from concussion. The objective of this study was to determine if the number of days to symptom resolution varied between collegiate athletes with or without sleep-related symptoms following a concussion. DESIGN: Retrospective chart review. METHODS: Collegiate athletes (n = 539) who were diagnosed with a concussion between the 2015-2020 sport seasons participated in this retrospective chart review. Participants were divided into groups based on the presence or absence of sleep symptoms within 72 hours of a diagnosed concussion. A Mann-Whitney U test was used to compare days to symptom resolution between groups with α = 0.05. RESULTS: Of the 539 participants, 250 (46.3%) reported sleep-related symptoms. Participants with sleep-related symptoms took significantly longer (U = 30656, p = 0.002) to report symptom resolution at rest (median [full range] = 8.00[0-423]) as compared to participants who did not report sleep-related symptoms (6.00[0-243] days). CONCLUSION: Collegiate athletes that report sleep-related symptoms immediately following concussion (<72 hours) were observed to take, on median, two days longer to achieve symptom resolution at rest when compared to athletes who did not endorse the same symptoms.

Sport Type and Risk of Subsequent Injury in Collegiate Athletes Following Concussion: a LIMBIC MATARS Consortium Investigation.

OBJECTIVE: To investigate the association between sport type (collision, contact, non-contact) and subsequent injury risk following concussion in collegiate athletes. MATERIALS AND METHODS: This retrospective chart review of 248 collegiate athletes with diagnosed concussions (age: 20.0 ± 1.4 years; height: 179.6 ± 10.9 cm; mass: 79.0 ± 13.6 kg, 63% male) from NCAA athletic programs (n = 11) occurred between the 2015-2020 athletic seasons. Acute injuries that occurred within six months following concussion were evaluated. Subsequent injuries were grouped by lower extremity, upper extremity, trunk, or concussion. The independent variable was sport type: collision, contact, non-contact. A Cox proportional hazard model was used to assess the risk of subsequent injury between sport types. RESULTS: Approximately 28% (70/248) of athletes sustained a subsequent acute injury within six months post-concussion. Collision sport athletes had a significantly higher risk of sustaining any injury (HR: 0.41, p < 0.001, 95% CI: 0.28, 0.62), lower extremity (HR: 0.55, p = 0.04, 95% CI: 0.32, 0.97), and upper extremity (HR: 0.41, p = 0.01, 95% CI: 0.20, 0.81) injuries following concussion. No differences between sport types were observed for other injuries. CONCLUSION: Collision sport athletes had a higher rate of any subsequent injury, lower, and upper extremity injuries following concussion. Future research should focus on sport-specific secondary injury prevention efforts.

Access to athletic trainers and sex as modifiers of time to reach clinical milestones after sport-related concussion in collegiate athletes.

OBJECTIVE: Investigate whether an athlete's biological sex and exposure to a dedicated athletic trainer (AT) were related to clinical milestones after a sports-related concussion (SRC). DESIGN: Retrospective chart review. METHODS: Medical charts of collegiate athletes (n = 196 [70.9% female]) diagnosed with SRC were reviewed to extract: biological sex, dedicated AT exposure for their sport (yes/no), and time (days) to reaching clinical milestones (diagnosis, symptom resolution, unrestricted return to sport [RTS]). Mann-Whitney U tests were used to determine whether time to clinical milestones differed by sex, AT exposure, or their interaction. Proportions of same-day diagnoses and times to diagnosis, symptom resolution, and unrestricted RTS were evaluated with chi-squared and spearman's rank correlations, respectively. RESULTS: There were no significant differences in times to reaching any clinical milestone by sex, AT exposure, or their interaction (ps > 0.05). Forty-three percent of participants were diagnosed on the day of their SRC. This did not differ by sex or AT exposure (ps > 0.29). Longer times to SRC diagnosis were associated with more days to symptom resolution (ρ = 0.236, p = 0.001) and unrestricted RTS (ρ = 0.223, p < 0.001). CONCLUSIONS: Athlete sex and AT exposure were not associated with times to reach any clinical milestone; however, delayed diagnosis was associated with longer times to reach clinical recovery.

Concussion diagnosis and recovery in relation to collegiate athletic department classification: a LIMBIC MATARS consortium investigation.

PURPOSE: We investigated time to reach concussion diagnosis and recovery milestones in collegiate athletes relative to their schools' National Collegiate Athletic Association (NCAA) classification. METHODS: We retrospectively examined 849 (43.1% female) concussion cases from 11 NCAA institutions (Division I Power 5 [n = 4], Division I Non-Power 5 [n = 4], and Division II/III [n = 3]) from the 2015-16 to 2019-20 athletic seasons. Our primary outcome measures were days to reach specific clinical milestones following concussion. RESULTS: Median (IQR) time from injury to diagnosis was significantly longer at Division II/III institutions (1 [0-4] days) compared to Division I Power 5 (0 [0-1] days) and Division I Non-Power 5 (0 [0-1] days) institutions (p < 0.001). Likewise, Division II/III athletes (15 [11-22] days) took significantly longer to return to sport after concussion than Division I Power 5 (10 [7-16] days) and Division I Non-Power 5 (11 [7-18.5] days) athletes (p < 0.001). CONCLUSION: Division II/III athletes had delayed concussion diagnoses and return to sport timelines compared to Division I athletes. Our results suggest that differences in sports medicine resources across NCAA divisions may influence injury recognition and recovery in collegiate athletes with concussion.

Physical activity and recovery following concussion in collegiate athletes: a LIMBIC MATARS Consortium Investigation.

OBJECTIVE: To investigate whether routine daily activities (RDA), non-prescribed exercise (Non-ERx), or prescribed exercise (ERx) were associated with recovery from sport-related concussion (SRC) in collegiate athletes. MATERIALS AND METHODS: Data for this cross-sectional, retrospective chart review of collegiate athletes diagnosed with SRC (n = 285[39.6% female], age = 19.5 ± 1.4 years) were collected during the 2015-16 to 2019-20 athletic seasons. The independent variable was group (RDA, Non-ERx, ERx). Dependent variables included days from date of diagnosis to symptom resolution (Dx-SR) and SR to return to sport (SR-RTS). RESULTS: Those in the Non-ERx group took nearly 1.3 times longer to achieve SR (IRR = 1.28, 95% CI: 1.11, 1.46) and, 1.8 times longer for RTS (IRR = 1.82, 95% CI: 1.11, 2.71) when compared to those in the RDA group. No other comparisons were significant. CONCLUSION: Collegiate athletes in the Non-ERx group took approximately 1 week longer to achieve SR as compared to the RDA and ERx groups. Our findings suggest that if exercise is recommended following SRC, it must be clearly and specifically prescribed. If exercise parameters cannot be prescribed, or monitored, RDA appear to be similarly beneficial during recovery for collegiate athletes with concussion.

Exploring the relationship between contraceptive medication use and concussion recovery in female collegiate athletes: a LIMBIC MATARS consortium investigation.

OBJECTIVE: While recovery from concussion is variable, women are more likely to report symptoms, experience worse outcomes, and have longer recovery trajectories following concussion than men. Preliminary data suggest that hormonal fluctuations, specifically progesterone, may be associated with this variability. This study aimed to understand the effect of contraceptive medication on concussion recovery. METHODS: A retrospective chart review using consensus-based common data elements was conducted at 11 NCAA institutions as part of the LIMBIC MATARS consortium. Participants included female collegiate athletes diagnosed with a concussion who did (n = 117) or did not report (n = 339) contraceptive medication use. Number of days between diagnosis and symptom resolution were compared using Mann-Whitney U tests. Self-reported diagnosis of attention deficit hyperactivity disorder, concussion history, anxiety, and depression was compared using Chi-squared tests. RESULTS: The proportions of participants who did or did not take contraceptive medication were similar across covariates. Female athletes regardless of contraceptive medication use recovered similarly following a concussion. CONCLUSIONS: Our findings suggest that contraceptive medication use did not significantly impact concussion recovery. Future prospective investigations should examine documentation practices and operationalize terminology for hormonal contraceptive medication to better understand their role on recovery from sport-related concussion in female collegiate athletes.

The influence of ADHD on recovery from sport concussion among collegiate athletes in the United States: LIMBIC MATARS consortium investigation.

OBJECTIVE: The present study aimed to assess the potential influence of a diagnosis of ADHD on concussion recovery among collegiate athletes. DESIGN: Retrospective and cross-sectional. METHODS: Data were extracted retrospectively from medical records across LIMBIC MATARS member institutions (n = 11), representing 1,044 concussion cases among collegiate athletes. After exclusions, 406 concussions were included in our analysis (ADHD: n = 38, age = 20.2 ± 1.67 years, 18.4% female; No ADHD: n = 368, age = 19.8 ± 1.39 years, 40.1% female). Mann-Whitney U tests were used to compare days from injury to diagnosis, symptom resolution, and return to sport among athletes with and without ADHD. RESULTS: No differences were observed for days from concussion until diagnosis (z = -0.33, p = 0.74), until days to symptom resolution (z = -1.30, p = 0.19), or days until return to sport (z = -0.68, p = 0.49); among concussion cases with or without a previously reported diagnosis of ADHD. CONCLUSION: Our findings further expand the literature that suggests ADHD is not strongly associated with recovery trajectory following sport concussion in collegiate athletes. Future research should extend these findings to be inclusive of additional preexisting health conditions and moderating effects related to medication usage among diverse athlete levels.

Academic adjustments and concussion recoveries in NCAA student-athletes: a LIMBIC MATARS investigation.

OBJECTIVE: The aim of this study was to investigate the association between academic adjustments and recovery from sport-related concussions (SRCs) in collegiate athletes. MATERIALS AND METHODS: A retrospective medical chart review was performed between the 2015-2016 and 2019-2020 sport seasons at 11 Long-term Impact of Military-relevant Brain Injury Consortium Military and Tactical Athlete Research Study (LIMBIC MATARS) sites. Days between injury and symptom resolution, and injury and return to sport (dependent variables) for collegiate athletes who did or did not receive academic adjustments (independent variable) were analyzed using Mann-Whitney U tests. RESULTS: The number of days between date of injury and symptom-resolution between those who did (median = 9 [interquartile range = 5,16]) and did not have (7[3,12]) academic adjustments were statistically different (z=-2.76, p < 0.01, r=-0.17). However, no differences were observed between days to return to sport among those who did (14[10,22]) and did not (13[8,20]) receive assigned academic adjustments (z= -1.66, p = 0.10, r= -.10). CONCLUSIONS: Recovery trajectories were similar between athletes diagnosed with a SRC who did or did not receive academic adjustments.. Our findings suggest academic adjustments supported recovery for those who needed academic adjustments. Clinicians and healthcare professionals should assist and support collegiate athletes after SRCs on an individual basis, including academic adjustments when appropriate based on patient presentation.

Effectiveness of care models for chronic disease management: A scoping review of systematic reviews.

OBJECTIVE: To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). METHODS: Information sources: Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. DATA: Target diseases, model components used (n = 11), and six outcomes (disease-specific, generic health-related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). SYNTHESIS: Narrative synthesis, including proportion of reviews documenting outcome benefits. RESULTS: More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes (n = 22), depression (n = 16), heart disease (n = 12), aging (n = 11), and kidney disease (n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease-specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. CONCLUSIONS: Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.

Brain Injury: How Dietary Patterns Impact Long-Term Outcomes.

Purpose of Review: Individuals with a history of traumatic brain injury (TBI) are at a much greater risk for developing cardiovascular disease (CVD) compared to the general population. This review discusses dietary patterns as a means of addressing modifiable risk factors following TBI exposure. Evidence-based resources for practicing Physiatrists and Brain Injury Medicine specialists pertaining to nutrition education and counseling are also provided. Recent Findings: We examined Mediterranean, Dietary Approaches to Stop Hypertension, plant-based, ketogenic, and intermittent fasting dietary patterns through publications of clinical trials and systematic reviews. While many reviews had significant positive findings, some were limited by generalizability. Summary: While there is extensive literature on the immediate nutrition goals in the inpatient setting following an acute TBI exposure, there is limited literature discussing the nature of diet and nutrition in the post-acute setting. Fortunately, most individuals with TBI exposure survive their initial injury and continue into the recovery phase. The scientific literature supports increased morbidity and mortality with chronic TBI exposure compared to matched counterparts, most notably with CVD. A diet rich in fiber and nutrients but limited in added sugars, saturated fats, and excess calories would likely have the greatest cardiovascular and related neurologic protection. Future studies are needed to assess the specific impact of dietary interventions in the chronic phase of brain injury recovery.

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

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

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium.

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.

Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study.

OBJECTIVE: While outcome from mild traumatic brain injury (mTBI) is generally favorable, concern remains over potential negative long-term effects, including impaired cognition. This study examined the link between cognitive performance and remote mTBIs within the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter, observational study of Veterans and service members (SMs) with combat exposure. METHOD: Baseline data of the participants passing all cognitive performance validity tests (n = 1,310) were used to conduct a cross-sectional analysis. Using multivariable regression models that adjusted for covariates, including age and estimated preexposure intellectual function, positive mTBI history groups, 1-2 lifetime mTBIs (nonrepetitive, n = 614), and 3 + lifetime mTBIs (repetitive; n = 440) were compared to TBI negative controls (n = 256) on each of the seven cognitive domains computed by averaging Z scores of prespecified component tests. Significance levels were adjusted for multiple comparisons. RESULTS: Neither of the mTBI positive groups differed from the mTBI negative control group on any of the cognitive domains in multivariable analyses. Findings were also consistently negative across sensitivity analyses (e.g., mTBIs as a continuous variable, number of blast-related mTBIs, or years since the first and last mTBI). CONCLUSIONS: Our findings demonstrate that the average veteran or SM who experienced one or more mTBIs does not have postacute objective cognitive deficits due to mTBIs alone. A holistic health care approach including comorbidity assessment is indicated for patients reporting chronic cognitive difficulties after mTBI(s), and strategies for addressing misattribution may be beneficial. Future study is recommended with longitudinal designs to assess within-subjects decline from potential neurodegeneration. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Employment of Neuromuscular Electrical Stimulation to Examine Muscle and Bone Qualities after Spinal Cord Injury.

(1) Background: Resource intensive imaging tools have been employed to examine muscle and bone qualities after spinal cord injury (SCI). We tested the hypothesis that surface neuromuscular electrical stimulation (NMES) amplitude can be used to examine knee extensor muscle quality, distal femur and proximal tibia bone mineral density (BMD) in persons with SCI. (2) Methods: Seventeen persons (2 women) with chronic SCI participated in three weeks of NMES-resistance training twice weekly of 4 sets of 10 repetitions. Participants were classified according to the current amplitude (>100 mA) and the number of repetitions (>70 reps) of leg extension into greater (n = 8; 1 woman; group A) and lower (n = 9; 1 woman; group B) musculoskeletal qualities. Magnetic resonance imaging, dual energy x-ray absorptiometry, isometric peak torque, Modified Ashworth and Penn spasm frequency scales were conducted. (3) Results: In between group comparisons, current amplitude was lower (38−46%) in group A. Whole (27−32%; p = 0.02), absolute (26−33%, p = 0.02) thigh muscle and absolute knee extensor muscle cross-sectional areas (22−33%, p = 0.04) were greater in group A. Right distal femur (24%; p = 0.08) and proximal tibia (29%; p = 0.03) BMDs were lower in group B, and peak isometric torque (p < 0.01), extensor spasticity scorers (p = 0.04) and muscle spasm scores (p = 0.002) were significantly higher in group A. Regression models revealed that amplitude of current, repetitions and body weight can accurately predict musculoskeletal qualities in persons with SCI. (4) Conclusions: Surface NMES amplitude and repetitions of leg extension differentiated between SCI survivors with greater versus lower musculoskeletal qualities. The study may shed the light on the interplay between muscle and bone in persons with SCI.

Testosterone and long pulse width stimulation (TLPS) for denervated muscles after spinal cord injury: a study protocol of randomised clinical trial.

INTRODUCTION: Long pulse width stimulation (LPWS; 120-150 ms) has the potential to stimulate denervated muscles and to restore muscle size in denervated people with spinal cord injury (SCI). We will determine if testosterone treatment (TT)+LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in persons with SCI with denervation. We hypothesise that the 1-year TT+LPWS will upregulate protein synthesis pathways, downregulate protein degradation pathways and increase overall mitochondrial health. METHODS AND ANALYSIS: Twenty-four male participants (aged 18-70 years with chronic SCI) with denervation of both knee extensor muscles and tolerance to the LPWS paradigm will be randomised into either TT+neuromuscular electrical stimulation via telehealth or TT+LPWS. The training sessions will be twice weekly for 1 year. Measurements will be conducted 1 week prior training (baseline; week 0), 6 months following training (postintervention 1) and 1 week after the end of 1 year of training (postintervention 2). Measurements will include body composition assessment using anthropometry, dual X-ray absorptiometry and MRI to measure size of different muscle groups. Metabolic profile will include measuring of basal metabolic rate, followed by blood drawn to measure fasting biomarkers similar to hemoglobin A1c, lipid panels, C reactive protein, interleukin-6 and free fatty acids and then intravenous glucose tolerance test to test for insulin sensitivity and glucose effectiveness. Finally, muscle biopsy will be captured to measure protein expression and intracellular signalling; and mitochondrial electron transport chain function. The participants will fill out 3 days dietary record to monitor their energy intake on a weekly basis. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board of the McGuire Research Institute (ID # 02189). Dissemination plans will include the Veteran Health Administration and its practitioners, the national SCI/D services office, the general healthcare community and the veteran population, as well as the entire SCI community via submitting quarterly letters or peer-review articles. TRIAL REGISTRATION NUMBER: NCT03345576.

Cerebral Microvascular Pathology Is a Common Endophenotype Between Traumatic Brain Injury, Cardiovascular Disease, and Dementia: A Hypothesis and Review.

Traumatic brain injury (TBI) exposure has been associated with an increased risk of age-related cognitive decline or dementia in multiple epidemiological studies. Current therapeutic interventions in the field of Brain Injury Medicine focus largely on episodic symptom management during the chronic phase of TBI recovery, rather than targeting specific underlying pathological processes. This approach may be especially problematic for secondary age-related cognitive decline or dementia following TBI exposure. Although there are likely multiple pathophysiological mechanisms involved, a growing body of literature demonstrates that cerebral microvascular pathology is a common endophenotype across the spectrum of TBI severity. Similarly, a combination of pre-clinical and clinical research over the past two decades has implicated cerebral microvascular pathology in the initiation and progression of multiple neurodegenerative diseases, including Alzheimer's disease and other dementias. We hypothesize that cerebral microvascular pathology is a common endophenotype between TBI, cardiovascular disease (CVD), and dementia, which can be targeted through modifiable cardiovascular risk factor reductions during the chronic phase of TBI recovery. We posit that our hypothesis is supported by the currently available scientific literature, as detailed in our review.

Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study.

OBJECTIVE: To determine if history of mild traumatic brain injury (mTBI) is associated with advanced or accelerated brain aging among the United States (US) military Service Members and Veterans. METHODS: Eight hundred and twenty-two participants (mean age = 40.4 years, 714 male/108 female) underwent MRI sessions at eight sites across the US. Two hundred and one participants completed a follow-up scan between five months and four years later. Predicted brain ages were calculated using T1-weighted MRIs and then compared with chronological ages to generate an Age Deviation Score for cross-sectional analyses and an Interval Deviation Score for longitudinal analyses. Participants also completed a neuropsychological battery, including measures of both cognitive functioning and psychological health. RESULT: In cross-sectional analyses, males with a history of deployment-related mTBI showed advanced brain age compared to those without (t(884) = 2.1, p = .038), while this association was not significant in females. In follow-up analyses of the male participants, severity of posttraumatic stress disorder (PTSD), depression symptoms, and alcohol misuse were also associated with advanced brain age. CONCLUSION: History of deployment-related mTBI, severity of PTSD and depression symptoms, and alcohol misuse are associated with advanced brain aging in male US military Service Members and Veterans.