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Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.
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Consumo Excesivo de Bebidas Alcohólicas , Veteranos , Sustancia Blanca , Humanos , Adulto , Adolescente , Encéfalo , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora , Consumo de Bebidas Alcohólicas , Consumo Excesivo de Bebidas Alcohólicas/diagnóstico por imagen , Etanol , AguaRESUMEN
PRIMARY OBJECTIVE: Despite a high prevalence of intimate partner violence (IPV) and its lasting impacts on individuals, particularly women, very little is known about how IPV may impact the brain. IPV is known to frequently result in traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). In this overview of literature, we examined literature related to neuroimaging in women with IPV experiences between the years 2010-2021. RESEARCH DESIGN: Literature overview. METHODS AND PROCEDURES: A total of 17 studies were included in the review, which is organized into each imaging modality, including magnetic resonance imaging (structural, diffusion, and functional MRI), Electroencephalography (EEG), proton magnetic resonance spectroscopy (pMRS), and multimodal imaging. MAIN OUTCOMES AND RESULTS: Research has identified changes in brain regions associated with cognition, emotion, and memory. Howeverto date, it is difficult to disentangle the unique contributions of TBI and PTSD effects of IPV on the brain. Furthermore, experimental design elements differ considerably among studies. CONCLUSIONS: The aim is to provide an overview of existing literature to determine commonalities across studies and to identify remaining knowledge gaps and recommendations for implementing future imaging studies with individuals who experience IPV.
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Lesiones Traumáticas del Encéfalo , Violencia de Pareja , Trastornos por Estrés Postraumático , Femenino , Humanos , Violencia de Pareja/psicología , Lesiones Traumáticas del Encéfalo/psicología , Emociones , Trastornos por Estrés Postraumático/epidemiología , Neuroimagen , Encéfalo/diagnóstico por imagenRESUMEN
RESEARCH QUESTION: Are semantic impairments in Alzheimer's disease (AD) partially due to deficits in spatial attention? METHODS AND RESULTS: In a target detection task, both older adults (OAs) and AD individuals were facilitated by valid spatial cues, but only OAs were impaired by invalid cues compared to neutral. In a reading task, spatial cues validly or invalidly cued the location of pictures, which were related or unrelated to subsequent, centrally presented, words. OAs showed semantic priming only after valid cues, whereas AD individuals showed priming after valid and invalid cues. DISCUSSION: Failure to inhibit uncued locations results in processing of potentially distracting semantic information in AD.
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Veterans who deployed in support of Operation Enduring Freedom (OEF), Iraqi Freedom (OIF), and New Dawn (OND) commonly experience severe psychological trauma, often accompanied by physical brain trauma resulting in mild traumatic brain injury (mTBI). Prior studies of individuals with posttraumatic stress disorder (PTSD) have revealed alterations in brain structure, accelerated cellular aging, and impacts on cognition following exposure to severe psychological trauma and potential interactive effects of military-related mTBI. To date, however, little is known how such deployment-related trauma changes with time and age of injury of the affected veteran. In this study, we explored changes in cortical thickness, volume, and surface area after an average interval of approximately 2 years in a cohort of 254 OEF/OIF/OND Veterans ranging in age from 19 to 67 years. Whole-brain vertex-wise analyses revealed that veterans who met criteria for severe PTSD (Clinician-Administered PTSD Scale ≥60) at baseline showed greater negative longitudinal changes in cortical thickness, volume, and area over time. Analyses also revealed a significant severe-PTSD by age interaction on cortical measures with severe-PTSD individuals exhibiting accelerated cortical degeneration with increasing age. Interaction effects of comorbid military-related mTBI within the severe-PTSD group were also observed in several cortical regions. These results suggest that those exhibiting severe PTSD symptomatology have accelerated atrophy that is exacerbated with increasing age and history of mTBI.
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Conmoción Encefálica , Enfermedades Neurodegenerativas , Trastornos por Estrés Postraumático , Veteranos , Adulto , Campaña Afgana 2001- , Anciano , Atrofia , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/epidemiología , Humanos , Guerra de Irak 2003-2011 , Persona de Mediana Edad , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/epidemiología , Veteranos/psicología , Adulto JovenRESUMEN
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood. METHOD: We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology. RESULTS: Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018-0.023, all p-values adjusted for multiple testing [padj ] < 0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß = -0.018, padj = 0.02) via AIM2 methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = -0.018, padj = 0.04) controlling for baseline IL-10. CONCLUSIONS: Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2 methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.
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Trastornos por Estrés Postraumático , Teorema de Bayes , Biomarcadores , Metilación de ADN/genética , Proteínas de Unión al ADN/genética , Epigénesis Genética , Humanos , Inflamación , Trastornos por Estrés Postraumático/complicacionesRESUMEN
OBJECTIVE: More than one-third of women in the United States experience intimate partner violence (IPV) in their lifetime, increasing their risk for traumatic brain injury (TBI). Despite the prevalence of TBI among IPV survivors, research is sparse in comparison with parallel populations (eg, military, accidents, sports). This pilot study aimed to provide a preliminary investigation of the effect of TBI on brain morphometry and resting-state functional connectivity in women who experience IPV. PARTICIPANTS: A total of 45 community-dwelling women survivors of IPV who screened positive for posttraumatic stress disorder (PTSD). DESIGN: Participants completed comprehensive assessments of trauma exposure, PTSD, TBI history, and brain neurological health. Twenty-three participants (51.1%) met diagnostic criteria for lifetime TBI. Of these, 15 participants experienced 1 or more TBIs resulting from IPV. The remaining participants experienced TBI from non-IPV exposures (eg, sports/motor vehicle accident). Surface-based neuroimaging analyses were performed to examine group differences in cortical thickness and in functional connectivity of amygdala and isthmus cingulate seeds to examine emotion regulation and the default mode network, respectively. MAIN MEASURES: Boston Assessment of Traumatic Brain Injury-Lifetime for Intimate Partner Violence (BAT-L/IPV); Clinician Administered PTSD Scale (CAPS); structural and functional neuroimaging. RESULTS: History of lifetime TBI in women IPV survivors was associated with differences in cortical thickness as well as functional connectivity between the isthmus cingulate seed and a variety of regions, including superior parietal and frontal cortices. Individuals with IPV-related TBI showed lower cortical thickness in the right paracentral gyrus than individuals with TBI from other non-IPV etiologies. CONCLUSION: Significant differences in brain structure and connectivity were observed in individuals with IPV and TBI. A lower mean cortical thickness of the paracentral gyrus was associated with TBI due to IPV than TBI from other etiologies. Although preliminary, findings from this pilot study present a step toward identifying potential mechanisms by which IPV and TBI secondary to IPV impact brain health in women.
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Lesiones Traumáticas del Encéfalo , Violencia de Pareja , Trastornos por Estrés Postraumático , Lesiones Traumáticas del Encéfalo/diagnóstico , Femenino , Neuroimagen Funcional/efectos adversos , Humanos , Violencia de Pareja/psicología , Proyectos Piloto , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/epidemiología , Sobrevivientes , Estados UnidosRESUMEN
The Clinician-Administered PTSD Scale (CAPS) is used to measure posttraumatic stress symptoms (PTSS) and diagnose posttraumatic stress disorder (PTSD). However, its use, particularly in settings involving longitudinal assessment, has been complicated by changes in the diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (i.e., DSM-IV and DSM-5, respectively). The current sample included trauma-exposed U.S. veterans who were deployed in support of military operations following the September 11, 2001, terrorist attacks (N = 371) and were enrolled in a longitudinal study focused on deployment-related stress and traumatic brain injury. A hybrid clinical interview using item wording from the CAPS for DSM-IV (CAPS-IV) with the addition of items unique to the CAPS for DSM-5 (CAPS-5) was used to assess both DSM-IV and DSM-5 PTSD diagnostic criteria, allowing for the calculation of separate total scores and diagnoses. Diagnostic agreement, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and interrater reliability between CAPS-IV and CAPS-5 were evaluated for the entire sample and stratified by gender. We found high diagnostic agreement (92.9%-95.4%), sensitivity (94.4%-98.2%), specificity (91.7%-92.8%), PPV (89.5%-93.0%), NPV (95.7%-98.1%), and interrater reliability,κ = 0.86-0.91,) for both men and women. The current study supports the use of a hybrid PTSD diagnostic interview assessing both DSM-IV and DSM-5 diagnostic criteria, particularly in situations such as longitudinal studies that may require a feasible method of incorporating changes in diagnostic criteria from the DSM-IV to the DSM-5.
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Trastornos por Estrés Postraumático , Veteranos , Femenino , Humanos , Masculino , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Estudios Longitudinales , Reproducibilidad de los Resultados , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
Recent-era U.S. veterans are clinically complex, with a high prevalence of co-occurring mild traumatic brain injury (mTBI), psychiatric conditions, and behavioral dysfunction. The current study examined the direct and indirect associations between mTBI and persistent neurobehavioral, psychiatric, and functional disability symptoms among recent-era U.S. veterans and service members (n = 648). We evaluated the postconcussive syndrome (PCS) potential causal model with two network analysis modeling approaches. Separate analyses were conducted for military mTBI and lifetime mTBI. An exploratory factor analysis was conducted to limit topological overlap in the network analysis. The most influential symptoms (i.e., the unique variables most strongly associated with the rest of the network) in the military mTBI network were behavioral disengagement, expected influence (EI) = 1.10; cognitive difficulties, EI = 1.08; agitation/irritability, EI = 1.05; and PTSD-related reexperiencing and avoidance symptoms, EI = 0.98. After accounting for other symptoms, mTBI was only minimally informative, EI = 0.34. Additionally, military mTBI did not moderate the association between symptoms or the overall connectivity of the network. The results for lifetime mTBI were consistent with those for military mTBI. The present analyses identified a variety of behavioral, cognitive, and emotional symptoms that play an important role in understanding comorbidity and daily functioning among recent-era U.S. veterans. Associations between cumulative mTBI that occurred in civilian or military settings were indirect and relatively small in magnitude. The current results add to a growing literature raising doubts about the PCS model.
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Conmoción Encefálica , Personal Militar , Síndrome Posconmocional , Trastornos por Estrés Postraumático , Veteranos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/epidemiología , Humanos , Síndrome Posconmocional/diagnóstico , Síndrome Posconmocional/epidemiología , Síndrome Posconmocional/etiología , Trastornos por Estrés Postraumático/psicología , Estados Unidos/epidemiología , Veteranos/psicologíaRESUMEN
Cross-sectional work suggests that deployment-related posttraumatic sequelae are associated with increased disability in U.S. veterans deployed following the September 11, 2001 (9/11), terrorist attacks. However, few studies have examined the psychiatric and somatic variables associated with changes in functional disability over time. A total of 237 post-9/11 veterans completed comprehensive assessments of psychiatric and cognitive functioning, as well as a disability questionnaire, at baseline and 2-year follow-up. At baseline, higher levels of PTSD, depressive, and pain-related symptoms were associated with baseline global functional disability, semipartial r2 = .036-.044. Changes in symptoms of PTSD, depression, pain, and sleep, but not anxiety or alcohol use, were independently associated with changes in functional disability, semipartial r2 = .017-.068. Baseline symptoms of these conditions were unrelated to changes in disability, and cognitive performance was unrelated to disability at any assessment point. Together, this suggests that changes in psychiatric and somatic symptoms are tightly linked with changes in functional disability and should be frequently monitored, and even subclinical symptoms may be a target of intervention.
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Personas con Discapacidad , Trastornos por Estrés Postraumático , Veteranos , Estudios Transversales , Humanos , Dolor , Trastornos por Estrés Postraumático/psicología , Veteranos/psicologíaRESUMEN
BACKGROUND: Post-9/11 veterans exhibit high prevalence of deployment stress, psychological conditions, and traumatic brain injury (TBI) which impact reintegration, especially among those with a history of interpersonal early life trauma (I-ELT). The relative importance of each risk factor is unclear. PURPOSE: We examined major deployment and clinical exposures of reintegration challenges among veterans with and without I-ELT. METHOD: We analyzed cross-sectional data of 155 post-9/11 veterans from the Translational Research Center for TBI and Stress Disorders study. FINDINGS: Depression severity had the strongest association with reintegration challenges, followed by posttraumatic stress disorder (PTSD) severity, post-deployment stress, and deployment safety concerns. Deployment safety concerns had a stronger, significant association among veterans with I-ELT. In nearly every model, PTSD and depression severities were weaker for veterans with I-ELT, compared to those without. DISCUSSION: Clinicians should consider the relative risk of concurrent clinical conditions and trauma histories when considering veterans' reintegration needs.
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Experiencias Adversas de la Infancia , Lesiones Traumáticas del Encéfalo , Trastornos por Estrés Postraumático , Veteranos , Campaña Afgana 2001- , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/psicología , Estudios Transversales , Depresión/epidemiología , Humanos , Guerra de Irak 2003-2011 , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Veteranos/psicologíaRESUMEN
Maladaptive anger and aggression are common in US military veterans and increase risk for impaired social relationships and functioning, justice-involvement and violence. Early life (before age 18) adversity predisposes veterans to later life psychopathology, though the link to increased later life anger is unclear. We analysed cross-sectional data of 158 post-9/11 veterans from the Translational Research Center for Traumatic Brain Injury and Stress Disorders study with and without a history of early life adversity (ns = 109 and 49, respectively). We explored the relationship among major clinical variables and current veteran anger (Dimensions of Anger Reactions) and whether the associations with these variables differed among participants with and without a history of retrospective self-reported early life adversity (Childhood Trauma Questionnaire). In the overall sample, posttraumatic stress disorder (PTSD) and depression severities had the strongest associations with current veteran anger (ßs = 0.261 and 0.263; p-values = 0.0022 and 0.0103, respectively). In the subsample without early life adversity, only PTSD severity was significantly associated with anger (ß = 0.577, p = 0.0004). In the early life adversity subsample, this strong association weakened and was no longer significant (ß = 0.168, p = 0.1007); instead, anxiety and depression severities showed moderate associations with anger (ßs = 0.243 and 0.287, p-values = 0.0274 and 0.0130, respectively). Findings suggest that clinicians should screen veterans with history of early life adversity for depression and anxiety when anger is present.
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Experiencias Adversas de la Infancia , Trastornos por Estrés Postraumático , Veteranos , Adolescente , Ira , Estudios Transversales , Humanos , Estudios Retrospectivos , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
BACKGROUND: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. METHODS: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. RESULTS: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. CONCLUSION: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
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Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (ß = -0.633), executive functioning (ß = -0.566), and global fractional anisotropy (ß = -0.470), such that elevated CRP was associated with worse cognition and white matter integrity in APOE ε4 carriers. Diffusion tensor imaging (DTI) was used to determine if CRP × APOE ε4 presence was associated with regionally specific fractional anisotropy in white matter tracts. Tract-based spatial statistics revealed CRP × APOE ε4 presence was associated with fractional anisotropy in the corpus callosum, right superior longitudinal fasciculus, right posterior corona radiata, as well as the bilateral anterior and superior corona radiatas. This suggests that APOE ε4 carriers may be uniquely vulnerable to the potentially negative impact of elevated systematic inflammation to cognition and microstructural white matter integrity.
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Apolipoproteína E4 , Proteína C-Reactiva , Cognición , Sustancia Blanca , Apolipoproteína E4/genética , Apolipoproteínas E , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Humanos , Pruebas Neuropsicológicas , Veteranos , Sustancia Blanca/diagnóstico por imagenRESUMEN
Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.
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Proteínas del Citoesqueleto/genética , Metilación de ADN , Cadenas beta de HLA-DP/genética , Trastornos por Estrés Postraumático , Epigénesis Genética , Epigenómica , Humanos , Trastornos por Estrés Postraumático/genéticaRESUMEN
BACKGROUND: Adolescence is a critical period for neural development and has been associated with high rates of alcohol abuse. This research examined potential long-term brain and behavioral effects of early versus late-onset adolescent binge drinking in an adult sample of post-9/11 Veterans. METHODS: We compared cortical thickness measures in Veterans with a history of binge drinking that began before the age of 15 (n = 50; mean age = 32.1 years) to those with a history of binge drinking with onset after the age of 15 (n = 300; mean age = 32.1 years). Data processing was conducted with FreeSurfer. A targeted neuropsychological battery (Digit Span test, Delis-Kaplan Executive Function System Color-Word Interference Test, California Verbal Learning Test-II) was used to examine the relationships between cortical thickness and attention, memory, and inhibition. A reference group of social drinkers with no history of early binge drinking (n = 31) was used to provide normative data. RESULTS: Early-onset adolescent binge drinkers (EBD) had greater cortical thickness in several regions than late-onset adolescent binge drinkers (LBD); both binge-drinking groups had greater cortical thickness than the reference group. There was a stronger negative association between cortical thickness and age in EBDs than LBDs in the (i) lateral orbitofrontal cortex, (ii) supramarginal gyrus, (iii) paracentral lobule, and (iv) anterior caudal cingulate. Poorer performance on the attention and inhibition tasks in the EBDs was also associated with thicker cortices. CONCLUSIONS: This study demonstrates greater cortical thickness across frontoparietal regions in adults who began binge drinking in early versus late adolescence. A stronger negative association between cortical thickness and age in the EBDs suggests that early-onset adolescent binge drinking may be associated with accelerated cortical thinning. Thicker cortex in these regions, which are known to mediate inhibitory control, may increase impulsive behavior and contribute to the risk of alcohol addiction.
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Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Grosor de la Corteza Cerebral , Corteza Cerebral/diagnóstico por imagen , Consumo de Alcohol en Menores/estadística & datos numéricos , Veteranos , Adolescente , Adulto , Edad de Inicio , Atención/fisiología , Consumo Excesivo de Bebidas Alcohólicas/diagnóstico por imagen , Consumo Excesivo de Bebidas Alcohólicas/fisiopatología , Corteza Cerebral/patología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/patología , Humanos , Inhibición Psicológica , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Tamaño de los Órganos , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/patología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiologíaRESUMEN
OBJECTIVE: Mobility limitation and cognitive decline are related. Metabolic syndrome (MetS), the clustering of three or more cardiovascular risk factors, is associated with decline in both mobility and cognition. However, the interrelationship among MetS, mobility, and cognition is unknown. This study investigated a proposed pathway where cognition moderates the relationship between MetS and Mobility. METHOD: Adults ages 45-90 years were recruited. MetS risk factors and mobility performance (Short Physical Performance Battery (SPPB) and gait speed) were evaluated. Cognition was assessed using a comprehensive neuropsychological battery. A factor analysis of neuropsychological test scores yielded three factors: executive function, explicit memory, and semantic/contextual memory. Multivariable linear regression models were used to examine the relationship among MetS, mobility, and cognition. RESULTS: Of the 74 participants (average age 61 ± 9 years; 41% female; 69% White), 27 (36%) participants manifested MetS. Mean SPPB score was 10.9 ± 1.2 out of 12 and gait speed was 1.0 ± 0.2 m/s. There were no statistically significant differences in mobility by MetS status. However, increase in any one of the MetS risk factors was associated with decreased mobility performance after adjusting for age and gender (SPPB score: ß (SE) -.17 (0.08), p < .05; gait speed: -.03 (.01), p < .01). Further adjusting for cognitive factors (SPPB score: explicit memory .31 (.14), p = .03; executive function 0.45 (0.13), p < .01; gait speed: explicit memory 0.04 (0.02), p = .03; executive function 0.06 (0.02), p < .01) moderated the relationships between number of metabolic risk factors and mobility. CONCLUSION: The relationship between metabolic risk factors and mobility may be moderated by cognitive performance, specifically through executive function and explicit memory.
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Síndrome Metabólico , Adulto , Anciano , Anciano de 80 o más Años , Cognición , Función Ejecutiva , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Limitación de la Movilidad , Pruebas NeuropsicológicasRESUMEN
OBJECTIVES: Recent studies suggest that close-range blast exposure (CBE), regardless of acute concussive symptoms, may have negative long-term effects on brain health and cognition; however, these effects are highly variable across individuals. One potential genetic risk factor that may impact recovery and explain the heterogeneity of blast injury's long-term cognitive outcomes is the inheritance of an apolipoprotein (APOE) ε4 allele, a well-known genetic risk factor for Alzheimer's disease. We hypothesized that APOE ε4 carrier status would moderate the impact of CBE on long-term cognitive outcomes. METHODS: To test this hypothesis, we examined 488 post-9/11 veterans who completed assessments of neuropsychological functioning, psychiatric diagnoses, history of blast exposure, military and non-military mild traumatic brain injuries (mTBIs), and available APOE genotypes. We separately examined the effects of CBE on attention, memory, and executive functioning in individuals with and without the APOE ε4 allele. RESULTS: As predicted, we observed a differential impact of CBE status on cognition as a function of APOE ε4 status, in which CBE ε4 carriers displayed significantly worse neuropsychological performance, specifically in the domain of memory. These results persisted after adjusting for clinical, demographic, and genetic factors and were not observed when examining other neurotrauma variables (i.e., lifetime or military mTBI, distant blast exposure), though these variables displayed similar trends. CONCLUSIONS: These results suggest APOE ε4 carriers are more vulnerable to the impact of CBE on cognition and highlight the importance of considering genetic risk when studying cognitive effects of neurotrauma.
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Apolipoproteína E4 , Cognición , Explosiones , Personal Militar , Veteranos , Apolipoproteína E4/genética , Genotipo , Humanos , Pruebas NeuropsicológicasRESUMEN
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.
Asunto(s)
Alcoholismo/epidemiología , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Conmoción Encefálica/epidemiología , Trastorno Depresivo/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Consumo de Alcohol en Menores/estadística & datos numéricos , Veteranos/estadística & datos numéricos , Adolescente , Adulto , Edad de Inicio , Alcoholismo/psicología , Conmoción Encefálica/psicología , Trastorno Depresivo/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/psicología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Adulto JovenRESUMEN
The human hippocampus is vulnerable to a range of degenerative conditions and as such, accurate in vivo measurement of the hippocampus and hippocampal substructures via neuroimaging is of great interest for understanding mechanisms of disease as well as for use as a biomarker in clinical trials of novel therapeutics. Although total hippocampal volume can be measured relatively reliably, it is critical to understand how this reliability is affected by acquisition on different scanners, as multiple scanning platforms would likely be utilized in large-scale clinical trials. This is particularly true for hippocampal subregional measurements, which have only relatively recently been measurable through common image processing platforms such as FreeSurfer. Accurate segmentation of these subregions is challenging due to their small size, magnetic resonance imaging (MRI) signal loss in medial temporal regions of the brain, and lack of contrast for delineation from standard neuroimaging procedures. Here, we assess the test-retest reliability of the FreeSurfer automated hippocampal subfield segmentation procedure using two Siemens model scanners (a Siemens Trio and Prismafit Trio upgrade). T1-weighted images were acquired for 11 generally healthy younger participants (two scans on the Trio and one scan on the Prismafit). Each scan was processed through the standard cross-sectional stream and the recently released longitudinal pipeline in FreeSurfer v6.0 for hippocampal segmentation. Test-retest reliability of the volumetric measures was examined for individual subfields as well as percent volume difference and Dice overlap among scans and intra-class correlation coefficients (ICC). Reliability was high in the molecular layer, dentate gyrus, and whole hippocampus with the inclusion of three time points with mean volume differences among scans less than 3%, overlap greater than 80%, and ICC >0.95. The parasubiculum and hippocampal fissure showed the least improvement in reliability with mean volume difference greater than 5%, overlap less than 70%, and ICC scores ranging from 0.78 to 0.89. Other subregions, including the CA regions, were stable in their mean volume difference and overlap (<5% difference and >75% respectively) and showed improvement in reliability with the inclusion of three scans (ICC â> â0.9). Reliability was generally higher within scanner (Trio-Trio), however, Trio-Prismafit reliability was also high and did not exhibit an obvious bias. These results suggest that the FreeSurfer automated segmentation procedure is a reliable method to measure total as well as hippocampal subregional volumes and may be useful in clinical applications including as an endpoint for future clinical trials of conditions affecting the hippocampus.
Asunto(s)
Hipocampo/anatomía & histología , Hipocampo/diagnóstico por imagen , Imagen por Resonancia Magnética/normas , Neuroimagen/normas , Reconocimiento de Normas Patrones Automatizadas/normas , Adulto , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Programas Informáticos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the association between traumatic brain injury (TBI) and nonfatal opioid overdose, and the role of psychiatric conditions as mediators of this association. SETTING: Post-9/11 veterans receiving care at national Department of Veterans Affairs (VA) facilities from 2007 to 2012. PARTICIPANTS: In total, 49 014 veterans aged 18 to 40 years receiving long-term opioid treatment of chronic noncancer pain. DESIGN: Longitudinal cohort study using VA registry data. MAIN MEASURES: TBI was defined as a confirmed diagnosis (28%) according to VA comprehensive TBI evaluation; no TBI was defined as a negative primary VA TBI screen (ie, no head injury). Nonfatal opioid overdose was defined using ICD-9 (International Classification of Diseases, Ninth Revision) codes. We performed demographic-adjusted Cox proportional hazards regression. We quantified the impact of co-occurring and individual psychiatric conditions (mood, anxiety, substance use, and posttraumatic stress disorder) on this association using mediation analyses. RESULTS: Veterans with TBI had more than a 3-fold increased risk of opioid overdose compared with those without (adjusted hazards ratio [aHR] = 3.22; 95% confidence interval [CI], 2.13-4.89). This association was attenuated in mediation analyses of any co-occurring psychiatric condition (aHR = 1.77; 95% CI, 1.25-2.52) and individual conditions (aHR range, 1.52-2.95). CONCLUSION: TBI status, especially in the context of comorbid conditions, should be considered in clinical decisions regarding long-term use of opioids in patients with chronic pain.