Suchergebnisse

OBJECTIVE: Since neurocognitive functioning following mild traumatic brain injury (mTBI) may be influenced by genetic factors that mediate synaptic survival and repair, we examined the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) on cognition using a well-defined sample of military Veterans with and without a history of mTBI. METHOD: Participants included 138 Veterans (mTBI=75; military controls [MCs]=63) who underwent neuropsychological testing, including completion of self-report measures assessing psychiatric distress, and BDNF genotyping. The mTBI group was tested roughly 66.7 months following their most recent mTBI. Veterans were divided into two groups—Met+ (Met/Met and Met/Val; n=49) and Met- (Val/Val; n=89) and compared on domain-specific cognitive composite scores representing memory, executive functioning, and visuospatial speed. RESULTS: ANCOVAs adjusting for psychiatric distress, sex, years of education, and ethnicity/race revealed a significant group (mTBI vs. MC) by BDNF genotype (Met+ vs. Met-) interaction for the memory (p=.024; η(p)(2)=.039) and executive functioning (p=.010; η(p)(2)=.050) composites, such that Met+ mTBI Veterans demonstrated better performance than Met- mTBI Veterans on the cognitive measures, whereas Met+ MCs demonstrated worse performance relative to Met- MCs on the cognitive measures. No significant interaction was observed for the visuospatial speed composite (p=.938; η(p)(2)<.001). CONCLUSIONS: These findings offer preliminary evidence to suggest that the Met allele may be protective in the context of remote mTBI. Findings need to be replicated using larger samples, and future studies are necessary to elucidate the precise mechanisms and neural underpinnings of this interaction.

INTRODUCTION: Our goal was to determine whether cognitive and cerebrospinal fluid (CSF) markers of tau and amyloid beta 1‐42 (Aβ(42)) differ between Vietnam‐era veterans with and without history of traumatic brain injury (TBI) and whether TBI moderates the association between CSF markers and neurocognitive functioning. METHODS: A total of 102 male participants (52 TBI, 50 military controls [MCs]; mean age = 68) were included. Levels of CSF Aβ(42), tau phosphorylated at the threonine 181 position (p‐tau), and total tau (t‐tau) were quantified. Group differences in CSF markers and cognition as well as the moderating effect of TBI on CSF and cognition associations were explored. RESULTS: Relative to MCs, the TBI group showed significantly higher p‐tau (P = .01) and t‐tau (P = .02), but no differences in amyloid (P = .09). TBI history moderated the association between CSF tau and performance on a measure of processing speed (t‐tau: P = .04; p‐tau: P = .02). DISCUSSION: Tau accumulation may represent a mechanism of dementia risk in older veterans with remote TBI.

As few studies have examined the relationship between the apolipoprotein E (APOE) gene and clinical outcomes after military-related traumatic brain injury (TBI), we aimed to determine whether the ε4 allele of the APOE gene influences neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI. Participants included 133 veterans (TBI = 79; military controls [MC] = 54) who underwent APOE genotyping and were divided into ε4(+) (TBI = 18; MC = 15) and ε4(–) (TBI = 61; MC = 39) groups. All participants underwent evaluation of psychological distress using the Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version. Two-way analyses of variance were conducted to examine the effect of group (TBI vs. MC) and APOE-ε4 status (ε4(+) vs. ε4(–)) across symptom measures. There was a significant main effect of group across all symptom measures (TBI > MC; all p values <0.001), no main effect of ε4 genotype (p = 0.152–0.222), and a significant interaction of group by ε4 genotype across all measures (p = 0.027–0.047). Specifically, for TBI participants, ε4(+) veterans demonstrated significantly higher symptom scores across all measures when compared to ε4(–) veterans (p = 0.007–0.015). For MC participants, ε4 status had no effect on the severity of psychiatric symptom scores (p = 0.585–0.708). Our results demonstrate that, in our well-characterized sample of veterans with history of neurotrauma, possession of the ε4 allele conveys risk for increased symptomatology (i.e., depression, anxiety, and post-traumatic stress disorder), even well outside of the acute phase of injury. Findings suggest a meaningful relationship between APOE genotype and psychiatric distress post-TBI, and they suggest that there is a brain basis for the complex neuropsychiatric presentation often observed in this vulnerable population. Future longitudinal studies are needed in order to further our understanding of how genetic factors influence response to TBI.

OBJECTIVE: The evaluation of memory complaints in mild traumatic brain injury (mTBI) remains an important clinical consideration especially in the context of comorbid psychiatric symptoms such as posttraumatic stress disorder (PTSD). We compared subjective memory complaints in Veterans with and without a history of mTBI, examined ratings between those with single versus multiple mTBIs, and investigated associations between memory complaints and PTSD symptom severity. METHODS: 117 outpatient Veterans (mTBI=79 [single-mTBI=22, multiple-mTBI=57], Military Controls (MCs)=38) completed a TBI history assessment, the Prospective-Retrospective Memory Questionnaire (PRMQ), and the PTSD Checklist-Military Version (PCL-M). RESULTS: Hierarchical multiple regression showed greater PCL-M scores significantly predicted elevated PRMQ-Total scores, accounting for 38% of the variance explained (p.50). CONCLUSIONS: Comorbid PTSD symptoms are an important factor when considering memory complaints in Veterans with a reported history of mTBI. However, independent of comorbid PTSD symptoms, mTBI status—particularly in the context of repetitive neurotrauma—uniquely contributes to memory complaints. Findings suggest Veterans with a history of multiple mTBIs may be a particularly vulnerable group in need of specialized interventions and/or psychoeducation.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.