Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias.

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways.

Impact and Risk of Moral Injury Among Deployed Veterans: Implications for Veterans and Mental Health.

The impact of "moral injury" (MI) among deployed veterans, defined as actions in combat that violate a veteran's moral beliefs and result in psychological distress, has increasingly become a significant clinical concern separate from other trauma- and stressor-related disorders. MI involves severe distress over violations of core beliefs often followed by feelings of guilt and conflict and is common among veterans with PTSD. While the psychological impact of PTSD is well-documented among veterans, this has been done less so with respect to MI. We studied MI among 1,032 deployed veterans who were outpatients in a large non-profit multi-hospital system in central Pennsylvania. The study included active duty and Guard/Reserve members, as well as veterans who were not Department of Veterans Affairs (VA) service users. Our hypothesis was that, controlling for other risk factors, veterans with high MI would have current mental disorders. Our secondary hypothesis was that MI would be associated with other psychopathologies, including chronic pain, sleep disorders, fear of death, anomie, and use of alcohol/drugs to cope post deployment. Most veterans studied were deployed to Vietnam (64.1%), while others were deployed to post-Vietnam conflicts in Iraq and Afghanistan and elsewhere. Altogether, 95.1% of the veterans were male and their mean age was 61.6 years (SD = 11.8). Among the veterans, 24.4% had high combat exposure, 10.9% had PTSD, 19.8% had major depressive disorder, and 11.7% had a history of suicidal thoughts. Based on the Moral Injury Events Scale (MIES), 25.8% had high MI post deployment, defined as a score above the 75th percentile. Results show that high MI among veterans was associated with current global mental health severity and recent mental health service use, but not suicidal thoughts. In addition, as hypothesized, MI was also associated with pain, sleep disorders, fear of death, anomie, use of alcohol/drugs to cope post-deployment, and poor unit support/morale during deployment. Deployed veterans with MI are more likely to have current mental health disorders and other psychological problems years after deployment. Further research is advised related to the screening, assessment, treatment, and prevention of MI among veterans and others after trauma exposures.

Genetic and Psychosocial Risk Factors Associated with Suicide Among Community Veterans: Implications for Screening, Treatment and Precision Medicine.

INTRODUCTION: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans. METHODS: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0-8, mean=3.6, SD=1.4). RESULTS: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p<0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p<0.001), history of depression (p>0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant. DISCUSSION: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.

Psychological well-being and alcohol misuse among community-based veterans: results from the Veterans' Health Study.

BACKGROUND: Maladaptive drinking is an increasing concern among military policy makers and healthcare providers. The goal of this study was to assess how social and psychological factors relate to alcohol problems among post-deployed US veterans and how problematic drinking is associated with well-being. METHODS: Data were collected via a telephone survey from a random sample of veterans receiving their healthcare from a large non-VA hospital system in central Pennsylvania (N = 1730). Interviewers inquired about participants' current alcohol consumption, using the CAGE and AUDIT-C scales, and health-related outcomes (general psychological distress, major depression, and self-reported health status). Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). RESULTS: Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). Analyses for our drinking measures show that those who used drugs or alcohol to cope post-deployment were more likely to be problematic drinkers, while positive personality characteristics such as agreeableness and conscientiousness were related to fewer drinking problems. Multivariate logistic regressions for our well-being measures found that alcohol misuse was not related to distress or depression, but that a positive score on the AUDIT-C was associated with a lower likelihood of poor self-rated health. Using alcohol or drugs to cope was related to higher distress. DISCUSSION: We conclude that service providers might consider using post-deployment AUDIT-C and the drugs and alcohol coping questions when screening for possible alcohol and mental health problems among veterans.

The ECLiPSE Procedure as an Alternative to Mastopexy following Implant Removal.

With the rise in number of breast implant removals for a variety of indications, strategies to improve aesthetic outcomes, while minimizing scars and operating time, will prove to be of benefit. We present here a novel periareolar sickle skin excision as a good option for women with mild to moderate ptosis and central loss of breast volume following implant removal/capsulectomy. METHODS: The ECLiPSE (Explant, Capsulectomy, Lift using Periareolar Sickle skin Excision) was utilized in 53 patients with a median follow-up of 24 weeks. RESULTS: The majority of these patients had breast implants for cosmetic augmentation and the most common indication for implant removal was capsular contracture (n = 47, 88.7%). Forty-six patients (86.8%) scored a high or very high satisfaction with the outcome of the procedure. CONCLUSION: We believe that the ECLiPSE procedure is a useful option that can produce a reasonable aesthetic outcome following implant removal/capsulectomy while minimizing visible scarring.

Risk and protective factors associated with mental health among female military veterans: results from the veterans' health study.

BACKGROUND: This study focuses on factors that may disproportionately affect female veterans' mental health, compared to men, and is part of a larger study assessing the prevalence of mental health disorders and treatment seeking among formerly deployed US military service members. METHODS: We surveyed a random sample of 1,730 veterans who were patients in a large non-VA hospital system in the US. Based on previous research, women were hypothesized to be at higher risk for psychological problems. We adjusted our results for confounding factors, including history of trauma, childhood abuse, combat exposure, deployments, stressful life events, alcohol misuse, psychological resources, and social support. RESULTS: Among the veterans studied, 5% were female (n = 85), 96% were White (n = 1,161), 22.9% were Iraq/Afghanistan veterans (n = 398), and the mean age was 59 years old (SD = 12). Compared to males, female veterans were younger, unmarried, college graduates, had less combat exposure, but were more likely to have lifetime PTSD (29% vs. 12%.), depression (46% vs. 21%), suicidal ideation (27% vs. 11%), and lifetime mental health service use (67% vs. 47%). Females were also more likely to have low psychological resilience and to have used psychotropic medications in the past year. Using multivariate logistic regression analyses that controlled for risk and protective factors, female veterans had greater risk for lifetime PTSD, depression, suicidal thoughts, and for lifetime use of psychological services, compared to males. Since 95% of the population in this study were male and these results may have been statistically biased, we reran our analyses using propensity score matching. Results were consistent across these analyses. CONCLUSION: Using a sample of post-deployment veterans receiving healthcare services from a large non-VA health system, we find that female veterans are at greater risk for lifetime psychological problems, compared to male veterans. We discuss these findings and their implications for service providers.

Pulsed Microwave Energy Transduction of Acoustic Phonon Related Brain Injury.

Pulsed microwaves above specific energy thresholds have been reported to cause brain injury in animal models. The actual physical mechanism causing brain damage is unexplained while the clinical reality of these injuries remains controversial. Here we propose mechanisms by which pulsed microwaves may injure brain tissue by transduction of microwave energy into damaging acoustic phonons in brain water. We have shown that low intensity explosive blast waves likely initiate phonon excitations in brain tissues. Brain injury in this instance occurs at nanoscale subcellular levels as predicted by physical consideration of phonon interactions in brain water content. The phonon mechanism may also explain similarities between primary non-impact blast-induced mild Traumatic Brain Injury (mTBI) and recent clinical and imaging findings of unexplained brain injuries observed in US embassy personnel possibly due to directed radiofrequency radiation. We describe experiments to elucidate mechanisms, RF frequencies and power levels by which pulsed microwaves potentially injure brain tissue. Pathological documentation of nanoscale brain blast injury has been supported experimentally using transmission electron microscopy (TEM) demonstrating nanoscale cellular damage in the absence of gross or light microscopic findings. Similar studies are required to better define pulsed microwave brain injury. Based upon existing findings, clinical diagnosis of both low intensity blast and microwave-induced brain injury likely will require diffusion tensor imaging (DTI), a specialized water based magnetic resonance imaging (MRI) technique.

Predictors of Current DSM-5 PTSD Diagnosis and Symptom Severity Among Deployed Veterans: Significance of Predisposition, Stress Exposure, and Genetics.

BACKGROUND: Previously we reported a genetic risk score significantly improved PTSD prediction among a trauma-exposed civilian population. In the current study, we sought to assess this prediction among a trauma-exposed military population. METHODS: We examined current PTSD diagnosis and PTSD symptom severity among a random sample of 1042 community-based US military veterans. Main effects and interaction effects were assessed for PTSD genetic risk by trauma exposure using cross-product terms for PTSD x trauma exposures, including combat, lifetime trauma, and adverse childhood exposures. The PTSD risk variants studied were within genetic loci previously associated with PTSD, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variants, which were used to calculate a total PTSD genetic risk score (range=0-8, mean=3.6, SD=1.4). RESULTS: Based on DSM-5 PTSD criteria, 7.1% of veterans (95% CI=5.6-8.8) met criteria for current PTSD. The PTSD genetic risk count was significantly higher among PTSD cases vs non-cases (3.92 vs 3.55, p=0.027). Since the PTSD genetic risk score was not significant in the PTSD diagnosis model, we assessed this association using PTSD symptom severity. Because these symptom data were skewed (mean=9.54, SD=12.71, range=0-76), we used negative binomial regression to assess this outcome. This symptom model included a PTSD genetic risk score, demographic factors, trauma exposures, current insomnia, current depression, concussion history, and attention-deficit disorder, expressed as incident rate ratios (IRR), which is an estimate of one-unit increase in PTSD severity, given other variables are held constant. Variables in the final model included age and sex (both p<0.001), PTSD genetic risk (IRR=1.02, p=0.028), warzone tours (IRR=0.94, p=0.003), childhood abuse (IRR=1.50, p<0.0001), current depression (IRR=1.89, p<0.0001), current insomnia (IRR=2.58, p<0.0001), low social support (IRR=1.19, p<0.0001), attention-deficit disorder (IRR=1.51, p<0.0001), agreeable personality (IRR=0.77, p<0.0001), and concussion (IRR=1.38, p<0.0001). Significant interactions were detected for combat and lifetime trauma exposure by PTSD genetic risk (both p<0.0001), suggesting that the impact of trauma exposures on PTSD severity was lower when the PTSD genetic risk was higher. CONCLUSION: Both warzone and non-warzone factors predicted current PTSD symptoms among veterans, including a PTSD genetic risk score. Interaction effects were detected for combat exposure and lifetime trauma by genetic risk score for PTSD symptoms, suggesting that PTSD symptom manifestation was more dependent on PTSD risk variants than the level of trauma or combat exposure. This suggests that controlling for other factors, the absence of genetic risk variants may confer PTSD resilience. Further research is planned.

Social and Psychological Risk and Protective Factors for Veteran Well-Being: The Role of Veteran Identity and Its Implications for Intervention.

Social psychological theory hypothesizes that one's identity, self-definitions, and meanings used for a particular social role fosters individual purpose in life and affects behavior in specific social situations. As such, it can be protective against the onset of psychological disorders. We examined this hypothesis with data collected from 1,730 military veterans recruited to study the health effects of warzone deployments. The sample was primarily male, older, and White. Our key independent variable was a Likert scale rating the prominence of a respondent's veteran identity: how important it is to the person. Outcome variables included posttraumatic stress disorder (PTSD), suicide ideation, depression, alcohol misuse, and use of VA services. Bivariate analysis suggested that veterans with a prominent veteran identity are older, noncollege graduates, have less income, and had their first deployment to Vietnam. In multivariate analyses, study participants with a prominent veteran identity were less likely to exhibit suicide ideation, but more likely to misuse alcohol and use VA services. We found no differences for PTSD, self-rated health, or depression by veteran identity. Veterans who scored higher on the veteran identity scale appeared to be protected from suicidal thoughts, although they had an elevated risk for alcohol misuse.

Grapheme-Color Synesthesia is Associated with PTSD Among Deployed Veterans: Confirmation of Previous Findings and Need for Additional Research.

Post-traumatic stress disorder (PTSD) is related to alteration in neuropsychological functioning, including visual and other cognitive processes. Grapheme-color synesthesia is a phenomenon in which a letter or number elicits response of a concurrent image or color perception. Since we earlier reported an association between grapheme-color synesthesia and PTSD, our objective in the current study was to validate this association among a new study group and assess risk factors. For this, we surveyed 1,730 military veterans who have been outpatients in the Geisinger Clinic, a multi-hospital system in Pennsylvania, USA. All the study veterans served in a warzone deployment. The association between PTSD and Grapheme-color synesthesia was evaluated. The average age of veterans was 59.6 years among whom 95.1% were male. Current PTSD prevalence rate was observed to be 7.6% (95% C.I. = 6.5-9.0) and in 3.4% of veterans (95% C.I. = 2.7-4.4) grapheme-color synesthesia was found to be positive. Initial bivariate analyses suggested that synesthesia was associated with current PTSD [odds ratio (OR) = 3.3, p<0.001]. Multivariable stepwise logistic regression evaluating the age, sex, education, trauma exposure, current psychological stress, psychotropic medication use, combat exposure, history of concussion, and current depression, confirmed this association (OR = 2.33, p = 0.019). The present study corroborated that Grapheme-color synesthesia was linked to PTSD among a second cohort of deployed military veterans. Further research is recommended in order to validate this observation and to determine whether synesthesia is a risk factor for PTSD.

Recommendations towards standards for quantitative MRI (qMRI) and outstanding needs.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

Mental Health Impact of Homecoming Experience Among 1730 Formerly Deployed Veterans From the Vietnam War to Current Conflicts: Results From the Veterans' Health Study.

We examined the effects of homecoming support on current mental health among 1730 deployed veterans from Vietnam, Iraq/Afghanistan, Persian Gulf, and other conflicts. The prevalence of current posttraumatic stress disorder (PTSD) was 5.4%, current depression was 8.3%, and 5.4% had suicidal thoughts in the past month. Overall, 26% of veterans had low homecoming support, which was more prevalent among Vietnam veterans (44.3%, p < 0.001). In multivariable logistic regressions, controlling for demographics, combat exposure, number of deployments, trauma history, and operational theater, low postdeployment support was associated with PTSD (odds ratio, 2.13; p = 0.032) and suicidality (odds ratio, 1.91; p < 0.030), but not depression. For suicidality, an interaction was detected for homecoming by theater status, whereby Iraq/Afghanistan veterans with lower homecoming support had a higher probability of suicidal thoughts (p = 0.002). Thus, years after deployment, lower homecoming support was associated with current PTSD and suicidality, regardless of theater and warzone exposures. For suicidality, lower support had a greater impact on Iraq/Afghanistan veterans.

Visual Dysfunction and Associated Co-morbidities as Predictors of Mild Traumatic Brain Injury Seen Among Veterans in Non-VA Facilities: Implications for Clinical Practice.

Introduction: Traumatic brain injury (TBI) and post-traumatic stress disorder are considered the signature injuries of the Iraq and Afghanistan conflicts. With the extensive use of improvised explosive devices by the enemy, the concussive effects from blast have a greater potential to cause mild TBI (mTBI) in military Service Members. These mTBI can be associated with other physical and psychological health problems, including mTBI-induced visual processing and eye movement dysfunctions. Our study assessed if any visual dysfunctions existed in those surveyed in non-Veterans Administration (VA) facilities who had suffered mTBI (concussive effect), in addition to the presence of concussion-related co-morbidities. Materials and Methods: As part of a larger study involving veterans from different service eras, we surveyed 235 Veterans who had served during the Iraq and/or Afghanistan conflict era. Data for the study were collected using diagnostic telephone interviews of these veterans who were outpatients of the Geisinger Health System. We assess visual dysfunction in this sample and compare visual dysfunctions of those who had suffered a mTBI (concussive effect), as well as co-morbidities, with those in the cohort who had not suffered concussion effects. Results: Of those veterans who experienced visual dysfunctions, our results reflected that the visual symptoms were significant for concussion with the subjects surveyed, even though all had experienced a mTBI event greater than five years ago. Although we did find an association with concussion and visual symptoms, the association for concussion was strongest with the finding of greater than or equal to three current TBI symptoms, therefore we found this to be the best predictor of previous concussion among the veterans. Conclusions: Veterans from the Iraq/Afghanistan era who had suffered concussive blast effects (mTBI) can present with covert visual dysfunction as well as additional physical and psychological health problems. The primary eye care providers, especially those in a non-military/VA facility, who encounter these veterans need to be aware of the predictors of mTBI, with the aim of uncovering visual dysfunctions and other associated co-morbidities.

Combat blast related traumatic brain injury (TBI): Decade of recognition; promise of progress.

Between April 2007 and December 2015, the Veterans Health Administration (VHA) screened one million combat veterans for traumatic brain injury (TBI), among 2.6 million deployed during operations Enduring Freedom, Iraqi Freedom and New Dawn (OEF/OIF/OND). Since 2007, among those reporting, screened and referred for definitive evaluation, approximately 8.4% of these Veterans received a diagnosis of TBI, the majority characterized as mTBI/Concussion (mTBI) and, in great proportion, related to blast exposures. Mild Traumatic brain injury called "a signature injury" is also known as 'the invisible injury' of these conflicts. Identifying and assessing neuropathological, cellular and resulting cognitive, emotional, behavioral and neurological consequences of mTBI comprise vast clinical and research challenges. We provide a brief overview of current history, injury mechanisms related to blast exposure, coordinated research support, and the need to understand specific cellular and neurological changes occurring with blast injury, particularly mTBI.

Social Support, Help-Seeking, and Mental Health Outcomes Among Veterans in Non-VA Facilities: Results from the Veterans' Health Study.

Using a stress process model, the authors examined social and psychological resources to better understand mental health outcomes among veterans. For this study, we surveyed 700 U.S. veterans who were outpatients in the Geisinger Health System. Independent variables included demographic factors, stressful and traumatic events, social support measures, and psychosocial factors. Using logistic regression, the authors examined 4 types of social connections: social support, help-seeking support, social capital, and other mental health support to predict mental health outcomes, including posttraumatic stress disorder, depression, suicide ideation, alcohol misuse, mental health service use, and Veterans Affairs service use. Results suggested that help-seeking support since deployment was a risk factor for 5 adverse outcomes, whereas social support was protective for 1 outcome. We concluded that high levels of help-seeking support since deployment among veterans was associated with a higher prevalence of mental health problems. These findings were unexpected and suggest the need for additional social support-related research among veterans.

Military Blast Injury and Chronic Neurodegeneration: Research Presentations from the 2015 International State-of-the-Science Meeting.

Blast-related traumatic brain injury (TBI) is a signature injury of recent military conflicts, leading to increased Department of Defense (DoD) interest in its potential long-term effects, such as chronic traumatic encephalopathy (CTE). The DoD Blast Injury Research Program Coordinating Office convened the 2015 International State-of-the-Science Meeting to discuss the existing evidence regarding a causal relationship between TBI and CTE. Over the course of the meeting, experts across government, academia, and the sports community presented cutting edge research on the unique pathological characteristics of blast-related TBI, blast-related neurodegenerative mechanisms, risk factors for CTE, potential biomarkers for CTE, and treatment strategies for chronic neurodegeneration. The current paper summarizes these presentations. Although many advances have been made to address these topics, more research is needed to establish the existence of links between the long-term effects of single or multiple blast-related TBI and CTE.

The Biological Basis of Chronic Traumatic Encephalopathy following Blast Injury: A Literature Review.

The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury. It served to inform participants objectively and help focus meeting discussion on identifying knowledge gaps and priority research areas. CTE is described generally as a progressive neurodegenerative disorder affecting persons exposed to head injury. Affected individuals have been participants primarily in contact sports and military personnel, some of whom were exposed to blast. The symptomatology of CTE overlaps with Alzheimer's disease and includes neurological and cognitive deficits, psychiatric and behavioral problems, and dementia. There are no validated diagnostic criteria, and neuropathological evidence of CTE has come exclusively from autopsy examination of subjects with histories of exposure to head injury. The perivascular accumulation of hyperphosphorylated tau (p-tau) at the depths of cortical sulci is thought to be unique to CTE and has been proposed as a diagnostic requirement, although the contribution of p-tau and other reported pathologies to the development of clinical symptoms of CTE are unknown. The literature on CTE is limited and is focused predominantly on head injuries unrelated to blast exposure (e.g., football players and boxers). In addition, comparative analyses of clinical case reports has been challenging because of small case numbers, selection biases, methodological differences, and lack of matched controls, particularly for blast-exposed individuals. Consequently, the existing literature is not sufficient to determine whether the development of CTE is associated with head injury frequency (e.g., single vs. multiple exposures) or head injury type (e.g., impact, nonimpact, blast-related). Moreover, the incidence and prevalence of CTE in at-risk populations is unknown. Future research priorities should include identifying additional risk factors, pursuing population-based longitudinal studies, and developing the ability to detect and diagnose CTE in living persons using validated criteria.

Animal Models for Tendon Repair Experiments: A Comparison of Pig, Sheep and Human Deep Flexor Tendons in Zone II.

BACKGROUND: This laboratory study compared pig, sheep and human deep flexor tendons in regards to their biomechanical comparability. METHODS: To investigate the relevant biomechanical properties for tendon repair experiments, the tendons resistance to cheese-wiring (suture drag/splitting) was assessed. Cheese-wiring of a suture through a tendon is an essential factor for repair gapping and failure in a tendon repair. RESULTS: Biomechanical testing showed that forces required to pulling a uniform suture loop through sheep or pig tendons in Zone II were higher than in human tendons. At time point zero of testing these differences did not reach statistical significance, but differences became more pronounced when forces were measured beyond initial cheese-wiring (2 mm, 5 mm and 10 mm). The stronger resistance to cheese-wiring was more pronounced in the pig tendons. Also regarding size and histology, sheep tendons were more comparable to human tendons than pig tendons. CONCLUSIONS: Differences in tendon bio-properties should be kept in mind when comparing and interpreting the results of laboratory tendon experiments.