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Despite affecting in 1 in every 1000 females, remarkably little is known about trisomy X syndrome (47,XXX), especially among older adults who are undiagnosed. In this study, we aimed to determine the prevalence of 47,XXX among females enrolled in the Million Veterans Program (MVP; mean age 50.2 ± 13.6 years), and compare broad health outcomes between females with 47,XXX and 46,XX matched controls. We identified 61 females with an additional X chromosome, corresponding to a prevalence of 103 per 100,000 females; 27.9% had been clinically diagnosed. Females with 47,XXX had taller stature (+6.1 cm, p < 0.001), greater rate of outpatient encounters (p = 0.026), higher odds of kidney disease (odds ratio [OR] = 12.3; 95% confidence interval [CI] 2.9-51.8), glaucoma (OR = 5.1; 95% CI 1.5-13.9), and congestive heart failure (OR = 5.6; 95% CI 1.4-24.2), and were more likely to be unemployed (p = 0.008) with lower annual income (p = 0.021) when compared with 46,XX controls of the same age and genetic ancestry. However, there were no differences in the rates of other encounter types, Charlson Comorbidity Index, all other medical and psychological diagnoses, military service history or quality of life metrics. In conclusion, in this aging and predominately undiagnosed sample, 47,XXX conferred few differences when compared with matched controls, offering a more reassuring perspective to the trisomy X literature.
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Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N = 304,485; 111,494 TBI cases, 192,991 controls). TBI was assessed using MVP survey data and International Classification of Diseases (ICD) codes from the Veterans Health Administration's electronic health record. GWAS was performed using logistic regression in PLINK, and meta-analyzed in METAL. FUMA was used for post-GWAS analysis. Genomic structural equation modeling (gSEM) was conducted to investigate underlying genetic associations with TBI, and bivariate MiXeR was used to estimate phenotype specific and shared polygenicity. SNP-based heritability was 0.060 (SE = 0.004, p = 7.83×10-66). GWAS analysis identified 15 genome-wide significant (GWS) loci at p < 5×10-8. Gene-based analyses revealed 14 gene-wide significant genes; top genes included NCAM1, APOE, FTO, and FOXP2. Gene tissue expression analysis identified the brain as significantly enriched, particularly in the frontal cortex, anterior cingulate cortex, and nucleus accumbens. Genetic correlations with TBI were significant for risk-taking behaviors and psychiatric disorders, but generally not significant for the neurocognitive variables investigated. gSEM analysis revealed stronger associations with risk-taking traits than with psychiatric traits. Finally, the genetic architecture of TBI was similar to polygenic psychiatric disorders. Neurodegenerative disorders including Alzheimer's and Parkinson's disease showed much less polygenicity, however, the proportion of shared variance with TBI was high. This first well-powered GWAS of TBI identified 15 loci including genes relevant to TBI biology, and showed that TBI is a heritable trait with comparable genetic architecture and high genetic correlation with psychiatric traits. Our findings set the stage for future TBI GWASs that focus on injury severity and diversity and chronicity of symptom sequelae.
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While genome wide association studies (GWASs) of Alzheimer's Disease (AD) in European (EUR) ancestry cohorts have identified approximately 83 potentially independent AD risk loci, progress in non-European populations has lagged. In this study, data from the Million Veteran Program (MVP), a biobank which includes genetic data from more than 650,000 US Veteran participants, was used to examine dementia genetics in an African descent (AFR) cohort. A GWAS of Alzheimer's disease and related dementias (ADRD), an expanded AD phenotype including dementias such as vascular and non-specific dementia that included 4012 cases and 18,435 controls age 60+ in AFR MVP participants was performed. A proxy dementia GWAS based on survey-reported parental AD or dementia (n = 4385 maternal cases, 2256 paternal cases, and 45,970 controls) was also performed. These two GWASs were meta-analyzed, and then subsequently compared and meta-analyzed with the results from a previous AFR AD GWAS from the Alzheimer's Disease Genetics Consortium (ADGC). A meta-analysis of common variants across the MVP ADRD and proxy GWASs yielded GWAS significant associations in the region of APOE (p = 2.48 × 10-101), in ROBO1 (rs11919682, p = 1.63 × 10-8), and RNA RP11-340A13.2 (rs148433063, p = 8.56 × 10-9). The MVP/ADGC meta-analysis yielded additional significant SNPs near known AD risk genes TREM2 (rs73427293, p = 2.95 × 10-9), CD2AP (rs7738720, p = 1.14 × 10-9), and ABCA7 (rs73505251, p = 3.26 × 10-10), although the peak variants observed in these genes differed from those previously reported in EUR and AFR cohorts. Of the genes in or near suggestive or genome-wide significant associated variants, nine (CDA, SH2D5, DCBLD1, EML6, GOPC, ABCA7, ROS1, TMCO4, and TREM2) were differentially expressed in the brains of AD cases and controls. This represents the largest AFR GWAS of AD and dementia, finding non-APOE GWAS-significant common SNPs associated with dementia. Increasing representation of AFR participants is an important priority in genetic studies and may lead to increased insight into AD pathophysiology and reduce health disparities.
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Enfermedad de Alzheimer , Negro o Afroamericano , Personal Militar , Anciano , Humanos , Persona de Mediana Edad , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/etnología , Enfermedad de Alzheimer/genética , Negro o Afroamericano/genética , Negro o Afroamericano/estadística & datos numéricos , Bases de Datos Genéticas/estadística & datos numéricos , Demencia/epidemiología , Demencia/etnología , Demencia/genética , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genotipo , Personal Militar/estadística & datos numéricos , Polimorfismo Genético , Estados Unidos/epidemiología , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genéticaRESUMEN
OBJECTIVE: In this cross-sectional study, the authors aimed to examine relationships between illness perception, measured as symptom attribution, and neurobehavioral and neurocognitive outcomes among veterans with a history of traumatic brain injury (TBI). METHODS: This study included 55 treatment-seeking veterans (N=43 with adequate performance validity testing) with a remote history of TBI (80% with mild TBI). Veterans completed a clinical interview, self-report questionnaires, and a neuropsychological assessment. A modified version of the Neurobehavioral Symptom Inventory (NSI) was administered to assess neurobehavioral symptom endorsement and symptom attribution. Composite scores were calculated from standardized cognitive tests to assess specific aspects of objective cognitive functioning, including memory, executive functioning, attention and working memory, and processing speed. RESULTS: The symptoms most frequently attributed to TBI included forgetfulness, poor concentration, slowed thinking, and headaches. There was a significant positive association between symptom attribution and overall symptom endorsement (NSI total score) (r=0.675) and endorsement of specific symptom domains (NSI symptom domain scores) (r=0.506-0.674), indicating that greater attribution of symptoms to TBI was associated with greater symptom endorsement. Furthermore, linear regressions showed that symptom attribution was significantly associated with objective cognitive functioning, whereas symptom endorsement generally did not show this relationship. Specifically, greater attribution of symptoms to TBI was associated with worse executive functioning (ß=-0.34), attention and working memory (ß=-0.43), and processing speed (ß=-0.35). CONCLUSIONS: These findings suggest that veterans who routinely attribute neurobehavioral symptoms to their TBI are at greater risk of experiencing poor long-term outcomes, including elevated symptom endorsement and worse objective cognition. Although more research is needed to understand how illness perception influences outcomes in this population, these preliminary results highlight the importance of early psychoeducation regarding the anticipated course of recovery following TBI.
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Conmoción Encefálica , Lesiones Traumáticas del Encéfalo , Trastornos por Estrés Postraumático , Veteranos , Humanos , Veteranos/psicología , Estudios Transversales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/psicología , Función Ejecutiva , Pruebas Neuropsicológicas , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.
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PURPOSE: To examine clinical outcomes and employment status in Veterans with and without a dual diagnosis of traumatic brain injury (TBI) and spinal cord injury (SCI). METHODS: This cross-sectional study examined a national sample of Veterans enrolled in the VA Million Veteran Program who completed the Comprehensive TBI Evaluation (CTBIE) as part of the Veterans Health Administration's TBI Screening and Evaluation Program. Veterans (N = 12,985) were classified into the following TBI/SCI groups using CTBIE data: those with a dual diagnosis of TBI and SCI (TBI+/SCI+); those with a history of TBI but no SCI (TBI+/SCI-); and those with no history of TBI or SCI (TBI-/SCI-; i.e., the control group). CTBIE-derived outcomes included neurobehavioral symptoms, comorbid psychiatric symptoms, pain and pain interference, and employment status. RESULTS: Chi-square analyses showed significant associations between TBI/SCI group and all clinical outcomes evaluated (all p's < .001; V = 0.07-0.11). In general, the TBI+/SCI+ and TBI +/SCI- groups endorsed comparable levels of neurobehavioral symptoms, psychiatric symptoms, and pain, but significantly greater rates of symptoms and pain relative to the TBI-/SCI- group. Effect sizes for all pairwise comparisons were small (φ = 0.01-0.11). Finally, there was no significant association between TBI/SCI group and employment status (p = .170; V = 0.02), with all three groups showing relatively comparable rates of unemployment. CONCLUSIONS: Regardless of SCI status, Veterans with TBI history endorsed poorer clinical outcomes than Veterans without TBI and SCI. However, rates of unemployment were similarly high across all three groups. Findings suggest that any Veteran completing the CTBIE may be at risk for poor clinical and employment outcomes.
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Lesiones Traumáticas del Encéfalo , Traumatismos de la Médula Espinal , Trastornos Relacionados con Sustancias , Veteranos , Humanos , Veteranos/psicología , Diagnóstico Dual (Psiquiatría) , Estudios Transversales , Calidad de Vida/psicología , Empleo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/epidemiología , Dolor , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiologíaRESUMEN
The purpose of this study was to develop and validate an algorithm for identifying Veterans with a history of traumatic brain injury (TBI) in the Veterans Affairs (VA) electronic health record using VA Million Veteran Program (MVP) data. Manual chart review (n = 200) was first used to establish 'gold standard' diagnosis labels for TBI ('Yes TBI' vs. 'No TBI'). To develop our algorithm, we used PheCAP, a semi-supervised pipeline that relied on the chart review diagnosis labels to train and create a prediction model for TBI. Cross-validation was used to train and evaluate the proposed algorithm, 'TBI-PheCAP.' TBI-PheCAP performance was compared to existing TBI algorithms and phenotyping methods, and the final algorithm was run on all MVP participants (n = 702,740) to assign a predicted probability for TBI and a binary classification status choosing specificity = 90%. The TBI-PheCAP algorithm had an area under the receiver operating characteristic curve of 0.92, sensitivity of 84%, and positive predictive value (PPV) of 98% at specificity = 90%. TBI-PheCAP generally performed better than other classification methods, with equivalent or higher sensitivity and PPV than existing rules-based TBI algorithms and MVP TBI-related survey data. Given its strong classification metrics, the TBI-PheCAP algorithm is recommended for use in future population-based TBI research.
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OBJECTIVES: Post-traumatic stress disorder (PTSD) and subjective cognitive decline (SCD) are independent risk factors for Alzheimer's disease (AD) and dementia, but the association of their interaction on AD biomarkers have yet to be characterized. This study aimed to examine the impact of PTSD on the association between SCD and tau and amyloid positron emission tomography (PET) as well as global cognition in older Veterans. METHOD: This study included 87 Vietnam-Era Veterans without dementia (42 with PTSD; 45 without PTSD) from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. All participants had both tau and amyloid PET imaging as well as cognitive testing. SCD was measured using the Everyday Cognition questionnaire. RESULTS: While SCD was associated with tau PET, amyloid PET, and global cognition, PTSD moderated these associations for tau and amyloid PET levels. Specifically, Veterans without PTSD had a stronger positive relationship between SCD and AD biomarkers when compared to those with PTSD. CONCLUSION: Higher SCD was associated with greater tau and amyloid burden and worse cognitive performance across the sample, though the tau and amyloid associations were stronger for Veterans without PTSD. Results highlight the potential benefit of comprehensive clinical assessments including consideration of mental health among older Veterans with SCD to understand the underlying cause of the cognitive concerns. Additionally, more work is needed to understand alternative mechanisms driving SCD in older Veterans with PTSD.
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OBJECTIVE: This study examined the moderating effect of traumatic brain injury (TBI) history on subjective and objective cognition across multiple cognitive domains. SETTING, PARTICIPANTS, AND DESIGN: Participants included 242 Vietnam-era veterans with a history of no TBI (n = 86), mild TBI (n = 74), or moderate-to-severe TBI (n = 82) from the observational Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) study. MAIN MEASURES: Objective cognition was the outcome and was measured using neuropsychological measures in the domains of memory, attention/executive functioning, and language. Subjective cognition was measured using the memory, divided attention, and language subscales from the Everyday Cognition (ECog) measure. TBI severity status was the moderating variable. RESULTS: Veterans with a history of moderate-to-severe TBI had a stronger negative association between subjective and objective attention relative to participants without a TBI (P = .002). Although this association did not differ between mild TBI and no TBI history groups (P = .100), the association between subjective and objective attention for the mild TBI group was intermediate to the no TBI and moderate-to-severe TBI history groups. TBI status did not moderate associations between subjective and objective memory or language. CONCLUSION: Results highlight the importance of assessing subjective and objective cognition in older veterans and the relevance of attention in the context of TBI history. More work is needed to better understand the intersection of TBI and aging and how these factors may be used to guide individualized assessment and treatment approaches for older veterans.
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Importance: Numerous studies have established the association of the common APOE ε2 and APOE ε4 alleles with Alzheimer disease (AD) risk across ancestries. Studies of the interaction of these alleles with other amino acid changes on APOE in non-European ancestries are lacking and may improve ancestry-specific risk prediction. Objective: To determine whether APOE amino acid changes specific to individuals of African ancestry modulate AD risk. Design, Setting, and Participants: Case-control study including 31â¯929 participants and using a sequenced discovery sample (Alzheimer Disease Sequencing Project; stage 1) followed by 2 microarray imputed data sets derived from the Alzheimer Disease Genetic Consortium (stage 2, internal replication) and the Million Veteran Program (stage 3, external validation). This study combined case-control, family-based, population-based, and longitudinal AD cohorts, which recruited participants (1991-2022) in primarily US-based studies with 1 US/Nigerian study. Across all stages, individuals included in this study were of African ancestry. Exposures: Two APOE missense variants (R145C and R150H) were assessed, stratified by APOE genotype. Main Outcomes and Measures: The primary outcome was AD case-control status, and secondary outcomes included age at AD onset. Results: Stage 1 included 2888 cases (median age, 77 [IQR, 71-83] years; 31.3% male) and 4957 controls (median age, 77 [IQR, 71-83] years; 28.0% male). In stage 2, across multiple cohorts, 1201 cases (median age, 75 [IQR, 69-81] years; 30.8% male) and 2744 controls (median age, 80 [IQR, 75-84] years; 31.4% male) were included. In stage 3, 733 cases (median age, 79.4 [IQR, 73.8-86.5] years; 97.0% male) and 19â¯406 controls (median age, 71.9 [IQR, 68.4-75.8] years; 94.5% male) were included. In ε3/ε4-stratified analyses of stage 1, R145C was present in 52 individuals with AD (4.8%) and 19 controls (1.5%); R145C was associated with an increased risk of AD (odds ratio [OR], 3.01; 95% CI, 1.87-4.85; P = 6.0 × 10-6) and was associated with a reported younger age at AD onset (ß, -5.87 years; 95% CI, -8.35 to -3.4 years; P = 3.4 × 10-6). Association with increased AD risk was replicated in stage 2 (R145C was present in 23 individuals with AD [4.7%] and 21 controls [2.7%]; OR, 2.20; 95% CI, 1.04-4.65; P = .04) and was concordant in stage 3 (R145C was present in 11 individuals with AD [3.8%] and 149 controls [2.7%]; OR, 1.90; 95% CI, 0.99-3.64; P = .051). Association with earlier AD onset was replicated in stage 2 (ß, -5.23 years; 95% CI, -9.58 to -0.87 years; P = .02) and stage 3 (ß, -10.15 years; 95% CI, -15.66 to -4.64 years; P = 4.0 × 10-4). No significant associations were observed in other APOE strata for R145C or in any APOE strata for R150H. Conclusions and Relevance: In this exploratory analysis, the APOE ε3[R145C] missense variant was associated with an increased risk of AD among individuals of African ancestry with the ε3/ε4 genotype. With additional external validation, these findings may inform AD genetic risk assessment in individuals of African ancestry.
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Enfermedad de Alzheimer , Apolipoproteína E4 , Población Negra , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Alelos , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Población Negra/genética , Estudios de Casos y Controles , Genotipo , Factores de Riesgo , Mutación MissenseRESUMEN
INTRODUCTION: Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer risk for Alzheimer's disease and related dementias (ADRD). METHODS: This study from the Million Veteran Program (MVP) evaluated the impact of apolipoprotein E (APOE) ε4, PTSD, and TBI on ADRD prevalence in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; n = 1443 ADRD cases, 16,191 controls). Additive-scale interactions were estimated using the relative excess risk due to interaction (RERI) statistic. RESULTS: PTSD, TBI, and APOE ε4 showed strong main-effect associations with ADRD. RERI analysis revealed significant additive APOE ε4 interactions with PTSD and TBI in the EA cohort and TBI in the AA cohort. These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles. DISCUSSION: PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Trastornos por Estrés Postraumático , Veteranos , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/genética , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Interacción Gen-Ambiente , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/genética , EnvejecimientoRESUMEN
PURPOSE: This study examined the clinical utility of post-traumatic stress disorder (PTSD), low resilience, poor sleep, and lifetime blast exposure as risk factors for predicting future neurobehavioral outcome following traumatic brain injury (TBI). METHODS: Participants were 591 U.S. military service members and veterans who had sustained a TBI (n = 419) or orthopedic injury without TBI (n = 172). Participants completed the Neurobehavioral Symptom Inventory, PTSD Checklist, and the TBI-Quality of Life (TBI-QOL) scale at baseline and follow-up. RESULTS: Using the four risk factors at baseline, 15 risk factor combinations were examined by calculating odds ratios to predict poor neurobehavioral outcome at follow-up (i.e., number of abnormal scores across five TBI-QOL scales [e.g., Fatigue, Depression]). The vast majority of risk factor combinations resulted in odds ratios that were considered to be clinically meaningful (i.e., ≥ 2.5) for predicting poor outcome. The risk factor combinations with the highest odds ratios included PTSD singularly, or in combination with poor sleep and/or low resilience (odds ratios = 4.3-72.4). However, poor sleep and low resilience were also strong predictors in the absence of PTSD (odds ratios = 3.1-29.8). CONCLUSION: PTSD, poor sleep, and low resilience, singularly or in combination, may be valuable risk factors that can be used clinically for targeted early interventions.
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Lesiones Traumáticas del Encéfalo , Personal Militar , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos por Estrés Postraumático , Veteranos , Lesiones Traumáticas del Encéfalo/complicaciones , Humanos , Estudios Longitudinales , Calidad de Vida/psicología , Factores de Riesgo , Sueño , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
OBJECTIVE: The purpose of this study was to examine the relationship between resilience and self-reported neurobehavioral functioning following traumatic brain injury (TBI) in U.S. military service members and veterans (SMVs). A secondary objective was to examine the interaction between resilience and posttraumatic stress disorder (PTSD) on neurobehavioral functioning. METHOD: Participants included 795 SMVs classified into four groups: Uncomplicated Mild TBI (MTBI; n=300); Complicated Mild, Moderate, Severe, or Penetrating TBI (STBI, n 162); Injured Controls (IC, n=185); and Non-injured Controls (NIC, n=148). Two independent cohorts were evaluated - those assessed within 1-year of injury and those assessed 10-years post-injury. SMVs completed self-report measures including the PTSD Checklist-Civilian version, Neurobehavioral Symptom Inventory, and TBI-Quality of Life. RESULTS: Results showed that (1) lower resilience was strongly associated with poorer neurobehavioral functioning across all groups at 1-year and 10-years post-injury, and (2) PTSD and resilience had a robust influence on neurobehavioral functioning at both time periods post-injury, such that SMVs with PTSD and low resilience displayed the poorest neurobehavioral functioning. CONCLUSION: Results suggest that regardless of injury group and time since injury, resilience and PTSD strongly influence neurobehavioral functioning following TBI among SMVs. Future research evaluating interventions designed to enhance resilience in this population is indicated.
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Lesiones Traumáticas del Encéfalo , Personal Militar , Trastornos por Estrés Postraumático , Veteranos , Lesiones Traumáticas del Encéfalo/complicaciones , Humanos , Calidad de Vida , Trastornos por Estrés Postraumático/complicacionesRESUMEN
OBJECTIVE: The purpose of this study was to evaluate whether loss of consciousness (LOC), retrograde amnesia (RA), and anterograde amnesia (AA) independently influence a particular aspect of post-concussion cognitive functioning-across-test intra-individual variability (IIV), or cognitive dispersion. METHOD: Concussed athletes (N = 111) were evaluated, on average, 6.04 days post-injury (SD = 5.90; Mdn = 4 days; Range = 1-26 days) via clinical interview and neuropsychological assessment. Primary outcomes of interest included two measures of IIV-an intra-individual standard deviation (ISD) score and a maximum discrepancy (MD) score-computed from 18 norm-referenced variables. RESULTS: Analyses of covariance (ANCOVAs) adjusting for time since injury and sex revealed a significant effect of LOC on the ISD (p = .018, ηp2 = .051) and MD (p = .034, ηp2 = .041) scores, such that athletes with LOC displayed significantly greater IIV than athletes without LOC. In contrast, measures of IIV did not significantly differ between athletes who did and did not experience RA or AA (all p > .05). CONCLUSIONS: LOC, but not RA or AA, was associated with greater variability, or inconsistencies, in cognitive performance acutely following concussion. Though future studies are needed to verify the clinical significance of these findings, our results suggest that LOC may contribute to post-concussion cognitive dysfunction and may be a risk factor for less efficient cognitive functioning.
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Traumatismos en Atletas , Conmoción Encefálica , Deportes , Atletas , Traumatismos en Atletas/complicaciones , Conmoción Encefálica/complicaciones , Cognición , Humanos , Pruebas Neuropsicológicas , Inconsciencia/etiologíaRESUMEN
OBJECTIVE: We examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms. METHOD: A total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA). RESULTS: After adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions. CONCLUSIONS: Veterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.
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Conmoción Encefálica , Trastornos por Estrés Postraumático , Veteranos , Sustancia Blanca , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Imagen de Difusión Tensora , Función Ejecutiva , Humanos , Pruebas Neuropsicológicas , Trastornos por Estrés Postraumático/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVE: The investigators sought to evaluate the independent and interactive associations between mild traumatic brain injury (mTBI) characteristics and posttraumatic stress disorder (PTSD) symptoms with regard to postconcussive symptoms and cognition among treatment-seeking veterans of the U.S. conflicts in Iraq and Afghanistan. METHODS: Sixty-seven Iraq and Afghanistan veterans who had a history of mTBI and comorbid PTSD were grouped based on injury mechanism (blast versus nonblast) and number of lifetime mTBIs (one to two versus three or more). Independent associations between mTBI characteristics and PTSD symptom clusters were evaluated with regard to cognition and postconcussive symptoms. Follow-up analyses were conducted to determine any interactive associations between TBI characteristics and PTSD symptom clusters. RESULTS: Higher PTSD symptoms, particularly hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. No direct relationships were observed between PTSD symptom clusters and memory or processing speed. The relationship between hyperarousal and processing speed was moderated by lifetime mTBIs, such that those with a history of at least three mTBIs demonstrated a negative association between hyperarousal and processing speed. Blast-related mTBI history was associated with reduced processing speed, compared with non-blast-related mTBI. However, an interaction was observed such that among those with blast-related mTBI history, higher re-experiencing symptoms were associated with poorer processing speed, whereas veterans without history of blast-related mTBI did not demonstrate an association between processing speed and re-experiencing symptoms. CONCLUSIONS: Higher hyperarousal and re-experiencing symptoms were associated with reduced processing speed among veterans with repetitive and blast-related mTBI history, respectively. PTSD symptoms, specifically hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. Limited associations were found between injury characteristics and cognition chronically following mTBI. However, these results support synergistic effects of specific PTSD symptom clusters and TBI characteristics.
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Campaña Afgana 2001- , Traumatismos por Explosión/complicaciones , Conmoción Encefálica/epidemiología , Cognición , Guerra de Irak 2003-2011 , Pruebas Neuropsicológicas/estadística & datos numéricos , Síndrome Posconmocional , Trastornos por Estrés Postraumático/epidemiología , Veteranos/estadística & datos numéricos , Adulto , Función Ejecutiva , Humanos , MasculinoRESUMEN
The purpose of this study was to examine the association between the apolipoprotein E (APOE) ε4 allele and neurocognitive functioning following traumatic brain injury (TBI) in military service members and veterans (SMVs). Participants included 176 SMVs with a history of remote TBI (≥1 year post-injury), categorized into mild (n = 100), moderate (n = 40), and severe (n = 36) TBI groups. Participants completed a neuropsychological assessment and APOE genotyping (n = 46 ε4+, n = 130 ε4-). Neurocognitive composite scores representing memory, executive functioning, and visual processing speed were computed. ANCOVAs adjusting for race, education, combat exposure, and PTSD symptom severity showed a significant main effect of ε4 on the memory composite, such that ε4+ SMVs exhibited poorer memory performance than ε4- SMVs. When ε2 allele carriers were removed from the analyses, associations with memory were strengthened, demonstrating a possible protective effect of the ε2 allele. No main effect of TBI group was identified on any cognitive composite, nor were there any significant TBI group × Îµ4 status interactions for any cognitive composite. Future studies with larger samples are needed to verify these findings, but our results suggest an important relationship between ε4 status and memory functioning following remote TBI of all severities.
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Apolipoproteínas E/genética , Lesiones Traumáticas del Encéfalo , Veteranos , Apolipoproteína E4/genética , Lesiones Traumáticas del Encéfalo/genética , Cognición , Genotipo , Humanos , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: To examine the association between employment status and neuropsychological functioning in veterans with a history of remote mild traumatic brain injury (mTBI) using 2 approaches to assess cognitive performance: (a) standard, traditional mean cognitive performance; and (b) across-test intraindividual variability (IIV). SETTING: Outpatient Veterans Affairs (VA) hospital. PARTICIPANTS: Eligibility criteria included veterans with a history of mTBI who performed adequately on performance validity tests. Participants (N = 75; 37 employed, 38 unemployed) were evaluated, on average, about 5.5 years after their most recent mTBI. DESIGN: Observational cohort study; all participants completed a clinical interview and a comprehensive neuropsychological assessment. MAIN MEASURES: Primary outcomes of interest included mean cognitive composite test scores and IIV scores on tasks of memory, attention/processing speed, and executive functioning. RESULTS: Logistic regression models showed that mean cognitive performance was not predictive of employment status; however, IIV indices were ( = 7.88, P = .048) and accounted for 13% of the variance. Greater memory-IIV was significantly associated with being unemployed (ß = -.16, SE = .07, P = .020, Exp(B) = 0.85; 95% CI, 0.74-0.98). CONCLUSION: These findings build upon prior work showing that IIV, or cognitive dispersion, is associated with important functional outcomes following mTBI, including employment status. Future studies are needed to verify these findings, but the present study suggests that IIV indices offer a clinically meaningful marker of cognitive functioning and should be considered when evaluating functional outcomes following head trauma.
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Desempleo , Veteranos , Cognición , HumanosRESUMEN
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: n = 79 [single mTBI: n = 22, multiple mTBI: n = 57], military controls [MCs]: n = 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 that greater PCL-M scores significantly predicted elevated PRMQ-Total scores, accounting for 38% of the variance explained (P < .001). mTBI status predicted an additional 5% of variance in memory complaints (P < .01). The multiple-mTBI group endorsed more memory complaints than either MCs (P < .01) or the single-mTBI group (P < .05), who did not differ from MCs (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 that veterans with a history of multiple mTBIs may be a particularly vulnerable group in need of specialized interventions and/or psychoeducation.
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Conmoción Encefálica , Trastornos por Estrés Postraumático , Veteranos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/epidemiología , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
OBJECTIVE: To examine self-efficacy and coping style in combat-exposed Veterans with and without mild traumatic brain injury (mTBI) history and posttraumatic stress disorder (PTSD). METHODS: Veterans (N = 81) were categorized into four groups: comorbid mTBI and PTSD (n = 23), PTSD-only (n = 16), mTBI-only (n = 25), and combat-exposed controls (n = 17). Outcomes included the Self-Efficacy for Symptom Management Scale and the Brief Coping Orientation to Problems Experienced. RESULTS: Significant group effects were found on self-efficacy and coping style, even when adjusting for total mTBIs and psychiatric comorbidities. Post-hoc analyses revealed that the comorbid and PTSD-only groups generally had lower self-efficacy than the mTBI-only and control groups and that the PTSD-only group used less action-focused coping than the mTBI-only and control groups. CONCLUSION: Our results suggest that self-efficacy and coping style vary as a function of mTBI history and PTSD status and that it may be important to integrate these malleable factors into interventions for this population.