Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI.

ObjectiveCerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI.Methods37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI.ResultsRegression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI.ConclusionsOur results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury

Blast-Exposed Veterans With Mild Traumatic Brain Injury Show Greater Frontal Cortical Thinning and Poorer Executive Functioning

Objective: Blast exposure (BE) and mild traumatic brain injury (mTBI) have been independently linked to pathological brain changes. However, the combined effects of BE and mTBI on brain structure have yet to be characterized. Therefore, we investigated whether regional differences in cortical thickness exist between mTBI Veterans with and without BE while on deployment. We also examined whether cortical thickness (CT) and cognitive performance differed among mTBI Veterans with low vs. high levels of cumulative BE.Methods: 80 Veterans with mTBI underwent neuroimaging and completed neuropsychological testing and self-report symptom rating scales. Analyses of covariance (ANCOVA) were used to compare blast-exposed Veterans (mTBI+BE, n = 51) to those without BE (mTBI-BE, n = 29) on CT of frontal and temporal a priori regions of interest (ROIs). Next, multiple regression analyses were used to examine whether CT and performance on an executive functions composite differed among mTBI Veterans with low (mTBI+BE Low, n = 22) vs. high (mTBI+BE High, n = 26) levels of cumulative BE.Results: Adjusting for age, numer of TBIs, and PTSD symptoms, the mTBI+BE group showed significant cortical thinning in frontal regions (i.e., left orbitofrontal cortex [p = 0.045], left middle frontal gyrus [p = 0.023], and right inferior frontal gyrus [p = 0.034]) compared to the mTBI-BE group. No significant group differences in CT were observed for temporal regions (p's > 0.05). Multiple regression analyses revealed a significant cumulative BE × CT interaction for the left orbitofrontal cortex (p = 0.001) and left middle frontal gyrus (p = 0.020); reduced CT was associated with worse cognitive performance in the mTBI+BE High group but not the mTBI+BE Low group.Conclusions: Findings show that Veterans with mTBI and BE may be at risk for cortical thinning post-deployment. Moreover, our results demonstrate that reductions in CT are associated with worse executive functioning among Veterans with high levels of cumulative BE. Future longitudinal studies are needed to determine whether BE exacerbates mTBI-related cortical thinning or independently negatively influences gray matter structure

Greater subjective cognitive decline severity is associated with worse memory performance and lower entorhinal cerebral blood flow in healthy older adults

ObjectiveSubjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.MethodsFifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).ResultsHigher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.ConclusionsOur preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline

Executive Functioning in Participants Over Age of 50 with Hoarding Disorder.

ObjectivesThe current investigation utilized mid-life and late-life participants diagnosed with hoarding disorder (HD) to explore the relationship between executive functioning and hoarding severity.DesignCorrelational analyses were used to investigate the associations between executive functioning and hoarding severity in nondemented participants. Multiple regression was used to determine if executive functioning had a unique association with HD severity when accounting for depressive symptoms.SettingParticipants were recruited from the San Diego area for HD intervention studies.ParticipantsParticipants were 113 nondemented adults aged 50-86 years who met DSM-5 criteria for HD. The mean age of the sample utilized in the analyses was 63.76 years (SD, 7.2; range, 51-85 years). The sample was mostly female (72%), Caucasian (81.4%), and unmarried (78%).MeasurementsHoarding severity was assessed using the Saving Inventory-Revised and the Clutter Image Rating and depression was assessed using the Hospital Anxiety and Depression Scale. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST-128) and the Trail Making and Verbal Fluency subtests of the Delis-Kaplan Executive Function System.ResultsExecutive function (operationalized as perseveration on the WCST-128) was significantly associated with Clutter Image Ratings. In a multivariate context, executive function and depressive symptom severity were both significant predictors of variance in Clutter Image Rating.ConclusionsOur results suggest that executive function is related to severity of HD symptoms and should be considered as part of the conceptualization of HD

Executive Functioning in Participants Over Age of 50 with Hoarding Disorder.

ObjectivesThe current investigation utilized mid-life and late-life participants diagnosed with hoarding disorder (HD) to explore the relationship between executive functioning and hoarding severity.DesignCorrelational analyses were used to investigate the associations between executive functioning and hoarding severity in nondemented participants. Multiple regression was used to determine if executive functioning had a unique association with HD severity when accounting for depressive symptoms.SettingParticipants were recruited from the San Diego area for HD intervention studies.ParticipantsParticipants were 113 nondemented adults aged 50-86 years who met DSM-5 criteria for HD. The mean age of the sample utilized in the analyses was 63.76 years (SD, 7.2; range, 51-85 years). The sample was mostly female (72%), Caucasian (81.4%), and unmarried (78%).MeasurementsHoarding severity was assessed using the Saving Inventory-Revised and the Clutter Image Rating and depression was assessed using the Hospital Anxiety and Depression Scale. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST-128) and the Trail Making and Verbal Fluency subtests of the Delis-Kaplan Executive Function System.ResultsExecutive function (operationalized as perseveration on the WCST-128) was significantly associated with Clutter Image Ratings. In a multivariate context, executive function and depressive symptom severity were both significant predictors of variance in Clutter Image Rating.ConclusionsOur results suggest that executive function is related to severity of HD symptoms and should be considered as part of the conceptualization of HD

REM Sleep Behavior Disorder in Parkinson’s Disease: Effects on Cognitive, Psychiatric, and Functional outcomes

ObjectiveRapid eye movement sleep behavior disorder (RBD) affects 33-46% of patients with Parkinson's disease (PD) and may be a risk factor for neuropsychological and functional deficits. However, the role of RBD on neuropsychological functioning in PD has yet to be fully determined. We, therefore, examined differences in neurocognitive performance, functional capacity, and psychiatric symptoms among nondemented PD patients with probable RBD (PD/pRBD+) and without (PD/pRBD-), and healthy comparison participants (HC).MethodsTotally, 172 participants (58 PD/pRBD+; 65 PD/pRBD-; 49 HC) completed an RBD sleep questionnaire, psychiatric/clinical questionnaires, performance-based and self-reported functional capacity measures, and underwent a comprehensive neuropsychological battery assessing attention/working memory, language, visuospatial function, verbal and visual learning and memory, and executive function.ResultsControlling for psychiatric symptom severity, the PD/pRBD+ group had poorer executive functioning and learning performance than the PD/pRBD- group and poorer neuropsychological functioning across all individual cognitive domains than the HCs. In contrast, PD/pRBD- patients had significantly lower scores than HCs only in the language domain. Moreover, PD/pRBD+ patients demonstrated significantly poorer medication management skills compared to HCs. Both PD groups reported greater depressive and anxiety severity compared to HCs; PD/pRBD+ group also endorsed greater severity of apathy compared to HCs.ConclusionsThe presence of pRBD is associated with poorer neuropsychological functioning in PD such that PD patients with pRBD have poorer cognitive, functional, and emotional outcomes compared to HC participants and/or PD patients without pRBD. Our findings underscore the importance of RBD assessment for improved detection and treatment of neuropsychological deficits (e.g., targeted cognitive interventions)

Psychometric Characteristics of the Insomnia Severity Index in Veterans With History of Traumatic Brain Injury

Objective/backgroundThe Insomnia Severity Index (ISI) is a widely used self-report measure of insomnia symptoms. However, to date this measure has not been validated or well-characterized in veterans who have experienced traumatic brain injury (TBI). This study assessed the psychometric properties and convergent, divergent, construct, and discriminate validity of the ISI in veterans with a history of TBI.ParticipantsEighty-three veterans with history of TBI were seen in the VA San Diego Healthcare System as part of a research protocol.MethodsMeasures included the ISI, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Neurobehavioral Symptom Inventory, Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version.ResultsThe ISI demonstrated moderate to strong or excellent convergent and divergent validity. A principal component analysis indicated a single construct with excellent internal consistency (Cronbach's alpha = 0.92). In exploratory analyses, the ISI discriminated well between those with (73%) and without (27%) sleep disturbance based on the PSQI.ConclusionsResults from this study indicate validity of the ISI in assessing insomnia in veterans with history of TBI and suggest a cutoff score not dissimilar from non-TBI populations. Findings from this study can help inform clinical applicability of the ISI, as well as future studies of insomnia in TBI

Dissociation of BDNF Val66Met polymorphism on neurocognitive functioning in military veterans with and without a history of remote mild traumatic brain injury

ObjectiveSince 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.MethodParticipants 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.ResultsANCOVAs 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; ηp 2 = .039) and executive functioning (p = .010; ηp 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; ηp 2 < .001).ConclusionsThese 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