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Objective Post-9/11 Veterans endorse greater self-reported functional disability than 80% of the adult population. Previous studies of trauma-exposed populations have shown that increased post-traumatic stress disorder (PTSD) and depressive symptoms are consistently associated with greater disability. Additionally, poorer cognitive performance in the domain of executive functions, particularly inhibitory control, has been associated with disability, though it is unclear if this effect is independent of and/or interacts with PTSD and depression. Method Three overlapping samples of n  = 582, 297, and 183 combat-deployed post-9/11 Veterans completed comprehensive assessments of executive functions, PTSD and depressive symptoms, and self-reported World Health Organization Disability Assessment Schedule-II (WHODAS II). Results Poorer performance on measures of inhibitory control (Delis-Kaplan Executive Functioning System Color-Word Interference-CWI Test and gradual-onset Continuous Performance Test-gradCPT), but not other executive functions, were significantly associated with greater disability on the WHODAS II (ρ's = −.13 and −.13, p  = .002 and.026, respectively). CWI inhibitory control measures accounted for unique variance in disability after controlling for PTSD and depressive symptoms (R 2 change = 0.02, p  < .001). Further, CWI significantly moderated the effect of depressive symptoms on disability, such that better inhibitory control weakened the relationship between depression and disability. Conclusions Inhibitory control deficits are uniquely associated with increased disability in combat-deployed post-9/11 Veterans, and better inhibitory control abilities may serve as a protective factor for depressive symptoms leading to increased disability. Key Points Question In a trauma-exposed Veteran population, does inhibitory control predict functional disability above and beyond PTSD and depressive symptoms? Findings After controlling for PTSD and depressive symptoms, inhibitory control explained unique variance in self-reported disability. Inhibitory control also showed a moderation effect on depression where greater inhibitory control on the color-word interference test reduced the association between depression and disability symptoms. Importance Inhibitory control represents an important mechanism in understanding and improving daily life functioning in trauma-exposed Veteran populations. Next Steps Future research should further characterize the different aspects of inhibitory control deficits in trauma-exposed populations and focus on enhancing inhibitory control paired with more standard psychological distress treatments. [ABSTRACT FROM AUTHOR]

Aims To demonstrate that early adolescent binge drinking (BD) increases the risk for and/or severity of psychopathology in post-9/11 Veterans and determine if mild traumatic brain injury (mTBI) modifies risk. Methods Post-9/11 Veterans (n = 375) were classified into two groups: 57 Veterans with a history of early adolescent BD (E-BD; age of onset <15) and 318 who did not BD until age 15 or older (late-BD or L-BD; age of onset ≥15). History of military mTBI and mental health disorders were also assessed following military service. Results Logistic regression and analysis of variance (ANOVA) analyses revealed that the E-BD's had significantly higher prevalence of alcohol use disorders (AUDs) and more severe symptoms of AUD, substance use disorder (SUD), depression and stress. Two-way ANOVAs showed that history of military mTBI was differentially associated with posttraumatic stress disorder (PTSD) incidence and severity among Veterans who had engaged in early adolescent BD. Specifically, Veterans with a history of both early adolescent BD and military mTBI were at greater risk for a PTSD diagnosis and had more severe symptoms of PTSD than those with only a history of adolescent BD. The greater PTSD symptom severity in the comorbid group was driven by hyperarousal symptoms. Conclusions A history of BD during early adolescence is prevalent among Veterans and is related to higher risk for AUD and more severe AUD, SUD, mood and stress symptoms later in life. Veterans with early BD and military mTBI showed greater incidence and severity of PTSD, indicating that mTBI, a common comorbidity among post-9/11 Veterans, exacerbates risk. [ABSTRACT FROM AUTHOR]

Studies of the association between traumatic brain injury (TBI) and suicide attempt have yielded conflicting results. Furthermore, no studies have examined the possible mediating role of common comorbid psychiatric conditions in this association. This study used Veterans Affairs registry data to evaluate the associations between deployment-related TBI, psychiatric diagnoses, and attempted suicide among 273,591 veterans deployed in support of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, and who received care from the Department of Veterans Affairs during 2007-2012. We performed Cox proportional hazards regression analyses, adjusting for demographic characteristics. Mediation analyses were conducted to quantify the impact of psychiatric conditions (posttraumatic stress disorder, depression, anxiety, and substance abuse) on this association. The sample was predominantly male (84%); mean age = 28.7 years. Veterans with TBI (16%) were more likely to attempt suicide than those without (0.54% vs. 0.14%): adjusted hazards ratio = 3.76, 95% confidence interval: 3.15, 4.49. This association was attenuated in mediation analyses (adjusted hazards ratio = 1.25, 95% confi- dence interval: 1.07, 1.46), with 83% of the association of TBI with attempted suicide mediated by co-occurring psychiatric conditions and with posttraumatic stress disorder having the largest impact. These results suggest that veterans with these conditions should be closely monitored for suicidal behavior. [ABSTRACT FROM AUTHOR]

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Objective. Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common among US veterans of Operation Enduring Freedom/ Operation Iraqi Freedom/Operation New Dawn (OEF/ OIF/OND). We postulated that these injuries may modulate pain processing in these individuals and affect their subjective pain levels. Design. Cross-sectional. Subjects. 310 deployed service members of OEF/ OIF/OND without a lifetime history of moderate or severe TBI were included in this study. Methods. All participants completed a comprehensive evaluation for Blast Exposure, mTBI, PTSD, and Pain Levels. The Boston Assessment of TBI-Lifetime Version (BAT-L) was used to assess blast exposure and potential brain injury during military service. The Clinician-Administered PTSD Scale (CAPS) characterized presence and severity of PTSD. The Visual Analog Scale (VAS) was used to assess pain intensity over the previous month before the interview, with higher scores indicative of worse pain. Statistical analysis was performed by ANOVA and results were adjusted for co-morbidities, clinical characteristics and demographic data. Results. In comparison to control participants (veterans without mTBI or current PTSD), veterans with both current PTSD and mTBI reported the highest pain intensity levels, followed by veterans with PTSD only (P<0.0001 and P = 0.0005, respectively). Pain levels in veterans with mTBI only were comparable to control participants. Conclusions. Comorbid PTSD and mTBI is associated with increased self-reported pain intensity. mTBI alone was not associated with increased pain. [ABSTRACT FROM AUTHOR]

Background: Pain related to many age-related chronic conditions is a burdensome problem in elderly adults and may also interfere with cognitive functioning. The purpose of this study was to examine the cross-sectional relationship between measures of pain severity and pain interference and cognitive performance in community-living older adults.Methods: We studied 765 participants in the Maintenance of Balance Independent Living Intellect and Zest (MOBILIZE) Boston Study, a population-based study of persons aged 70 and older. Global pain severity and interference were measured using the Brief Pain Inventory subscales. The neuropsychological battery included measures of attentional capacity (Trail Making Test A, WORLD Test), executive function (Trail Making Test B and Delta, Clock-in-a-Box, Letter Fluency), memory (Hopkins Verbal Learning Test), and a global composite measure of cognitive function. Multivariable linear regression models were used to analyze the relationship between pain and cognitive functioning.Results: Elderly adults with more severe pain or more pain interference had poorer performance on memory tests and executive functioning compared to elders with none or less pain. Pain interference was also associated with impaired attentional capacity. Additional adjustment for chronic conditions, behaviors, and psychiatric medication resulted in attenuation of many of the observed associations. However, the association between pain interference and general cognitive function persisted.Conclusions: Our findings point to the need for further research to understand how chronic pain may contribute to decline in cognitive function and to determine strategies that may help in preventing or managing these potential consequences of pain on cognitive function in older adults. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure-one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan-is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a 'dose-response' relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. [ABSTRACT FROM AUTHOR]

Homocysteine is a sulfur-containing amino acid that is involved in one-carbon metabolism. Hyperhomocysteinemia is a common phenomenon among elderly people. There is growing evidence of an association between hyperhomocysteinemia and geriatric multisystem problems, including coronary artery disease, stroke, peripheral vascular disease, cognitive impairment, dementia, depression, osteoporotic fractures, and functional decline. The proposed mechanisms of the association include angiotoxicity, neurotoxicity, and inhibition of collagen cross-linking. A homocysteine-lowering strategy may prevent or slow the development of these age-related problems. Vitamin supplementation and folic acid fortification of grain foods have been shown to decrease plasma homocysteine concentrations. More research is needed to investigate whether lifelong homocysteine lowering can prevent the development of late-life morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Post-traumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular and metabolic diseases and physical inactivity. Cardiorespiratory fitness (CRF), which is modifiable by physical activity, is a strong independent predictor of cardiometabolic health. However, the relationship between CRF and cardiometabolic health in veterans with PTSD is unknown. Thus, this study aimed to explore the cross-sectional relationships among CRF, indices of cardiometabolic health (ie, HbA1c, blood lipids, blood pressure, waist-hip ratio, and body mass index), and PTSD severity in veterans with PTSD.Materials and Methods: This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants (n = 13) completed a cardiopulmonary exercise test, a fasting blood draw, and the Clinician Administered PTSD Scale. Correlations between CRF and cardiometabolic health were examined with Spearman's rank correlations, and differences in PTSD symptom severity were explored as a function of CRF (ie, low-to-moderate vs. high CRF), using multiple linear regression.Results: Peak oxygen uptake ($\dot{\mathrm{V}}$O2peak) was correlated with high-density lipoproteins rho = 0.60, P = 0.04 and diastolic blood pressure rho = -0.56, P = 0.05. Ventilatory threshold was correlated with HbA1c rho = -0.61, P = 0.03 and diastolic blood pressure rho = -0.56, P = 0.05. Higher CRF was associated with lower total PTSD severity standardized β = -0.84, P = 0.01, adjusted R2 = 0.47, total Cluster C symptoms (avoidance/numbing) β = -0.71, P = 0.02, adjusted R2 = 0.49, and total Cluster D symptoms (hyperarousal) β = -0.89, P = 0.01, adjusted R2 = 0.41, while adjusting for age and smoking status.Conclusions: These preliminary findings suggest that CRF and by proxy physical activity may be important factors in understanding the increased risk of cardiovascular and metabolic disease associated with PTSD. [ABSTRACT FROM AUTHOR]