Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model.

The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.

HIV peripheral neuropathy-related degeneration of white matter tracts to sensorimotor cortex.

Human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) affects up to 50% of people with HIV and is associated with depression, unemployment, and generally worsened quality of life. Previous work on the cortical mechanism of HIV neuropathy found decreased gray matter volume in the bilateral midbrain, thalamus, and posterior cingulate cortex, but structural connectivity in this context remains under-studied. Here we examine alterations in white matter microstructure using diffusion imaging, hypothesizing that cortical white matter degeneration would be observed in continuation of the peripheral white matter atrophy previously observed in HIV-DSP. Male HIV seropositive patients (n = 57) experiencing varying degrees of HIV neuropathy underwent single-shell diffusion tensor imaging with 51 sampling directions. The scans were pooled using tractography and connectometry to create a quantitative map of white matter tract integrity, measured in generalized fractional anisotropy (GFA). The relationship between GFA and neuropathy severity was evaluated with linear regression. Correction for multiple comparisons was done using false discovery rate (FDR), a statistical method commonly used in genomics and imaging to minimize false positives when thousands of individual comparisons are made. Neuropathy severity was associated with decreased GFA along thalamocortical radiations leading along the lateral thalamus to sensorimotor cortex, with r = -0.405 (p < 0.001; FDR), as well as with the superior bilateral cingulum (r = -0.346 (p < 0.05; FDR)). Among a population of HIV neuropathy patients, greater neuropathy severity was correlated with lower white matter integrity running from midbrain to somatosensory cortex. This suggests ascending deafferentation extending from damaged peripheral nerves further downstream than seen previously, into the axons of third-order neurons. There is also evidence of cingulum degeneration, implying some more complex mechanism beyond the ascending atrophy observed here.

APOE modifies the interaction of entorhinal cerebral blood flow and cortical thickness on memory function in cognitively normal older adults.

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) gene increases risk for cognitive decline in normal and pathologic aging. However, precisely how APOE ε4 exerts its negative impact on cognition is poorly understood. The present study aimed to determine whether APOE genotype (ε4+ vs. ε4-) modifies the interaction of medial temporal lobe (MTL) resting cerebral blood flow (CBF) and brain structure (cortical thickness [CT], volume [Vo]) on verbal memory performance. METHODS: Multiple linear regression models were employed to investigate relationships between APOE genotype, arterial spin labeling MRI-measured CBF and FreeSurfer-based CT and Vo in four MTL regions of interest (left and right entorhinal cortex and hippocampus), and verbal memory performance among a sample of 117 cognitively normal older adults (41 ε4+, 76 ε4-) between the ages of 64 and 89 (mean age â€‹= â€‹73). RESULTS: Results indicated that APOE genotype modified the interaction of CBF and CT on memory in the left entorhinal cortex, such that the relationship between entorhinal CBF and memory was negative (lower CBF was associated with better memory) in non-carriers with higher entorhinal CT, positive (higher CBF was associated with better memory) in non-carriers with lower entorhinal CT, and negative (higher CBF was associated with worse memory) in ε4 carriers with lower entorhinal CT. CONCLUSIONS: Findings suggest that older adult APOE ε4 carriers may experience vascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect memory even in the absence overt clinical symptoms, providing potential insight into the mechanistic link between APOE ε4 and detriments in cognition. Moreover, findings suggest a distinct multimodal neural signature in ε4 carriers (higher CBF and lower CT in the entorhinal cortex) that could aid in the identification of candidates for future clinical trials aimed at preventing or slowing cognitive decline. Differential findings with respect to ε4 carriers and non-carriers are discussed in the context of neurovascular compensation.

Mild Traumatic Brain Injury Burden Moderates the Relationship Between Cognitive Functioning and Suicidality in Iraq/Afghanistan-Era Veterans.

OBJECTIVES: Suicidal ideation (SI) is highly prevalent in Iraq/Afghanistan-era veterans with a history of mild traumatic brain injury (mTBI), and multiple mTBIs impart even greater risk for poorer neuropsychological functioning and suicidality. However, little is known about the cognitive mechanisms that may confer increased risk of suicidality in this population. Thus, we examined relationships between neuropsychological functioning and suicidality and specifically whether lifetime mTBI burden would moderate relationships between cognitive functioning and suicidal ideation. METHODS: Iraq/Afghanistan-era Veterans with a history of mTBI seeking outpatient services (N = 282) completed a clinical neuropsychological assessment and psychiatric and postconcussive symptom questionnaires. RESULTS: Individuals who endorsed SI reported more severe post-traumatic stress disorder (PTSD), depression, and postconcussive symptoms and exhibited significantly worse memory performance compared to those who denied SI. Furthermore, mTBI burden interacted with both attention/processing speed and memory, such that poorer performance in these domains was associated with greater likelihood of SI in individuals with a history of three or more mTBIs. The pattern of results remained consistent when controlling for PTSD, depression, and postconcussive symptoms. CONCLUSIONS: Slowed processing speed and/or memory difficulties may make it challenging to access and use past experiences to solve current problems and imagine future outcomes, leading to increases in hopelessness and SI in veterans with three or more mTBIs. Results have the potential to better inform treatment decisions for veterans with history of multiple mTBIs. (JINS, 2019, 25, 79-89).

Subjective Cognitive Decline Modifies the Relationship Between Cerebral Blood Flow and Memory Function in Cognitively Normal Older Adults.

OBJECTIVES: Subjective cognitive decline (SCD), or self-reported cognitive decline despite normal neuropsychological test performance, is a risk factor for objective cognitive decline and Alzheimer's disease (AD). While brain mechanisms contributing to SCD are not well defined, studies show associations with vascular risk factors and altered cerebral blood flow (CBF), raising the hypothesis that those with SCD might be experiencing vascular dysregulation, or a disruption in the normal relationship between CBF and cognition. We examined whether the association between CBF and verbal memory performance differs between those with SCD (SCD+) and those without SCD (SCD-). METHODS: Linear mixed-effects models were used to investigate whether the voxel-wise relationship between arterial spin labeling (ASL) MRI-measured CBF and verbal memory performance was modified by SCD among a group of 70 cognitively normal older adults (35 SCD+, 35 SCD-; mean age=72) matched on age, gender, and symptoms of depression. RESULTS: Results indicated that the SCD- group exhibited positive associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, and inferior frontal gyrus, whereas the SCD+ group displayed negative associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, hippocampus, fusiform gyrus, and inferior frontal gyrus. CONCLUSIONS: Findings suggest that, while higher CBF is supportive of memory function in those without SCD, higher CBF may no longer support memory function in those presenting with SCD, perhaps reflecting neurovascular dysregulation. (JINS, 2018, 24, 213-223).

Correlates of employment and postsecondary education enrolment in Afghanistan and Iraq veterans with traumatic brain injuries.

PRIMARY OBJECTIVE: About 20% of Iraq and Afghanistan Veterans have sustained a traumatic brain injury (TBI), which can result in postconcussive symptoms and difficulty transitioning from the military to civilian employment and postsecondary education. To better inform programs help Veterans transition back into civilian life, we evaluated correlates of employment and postsecondary education enrolment among treatment-seeking Veterans with a history of TBI. RESEARCH DESIGN: A cross-sectional design, using an archival database of VA medical records, was used to answer these research questions. METHODS AND PROCEDURES: We examined demographic, TBI-related, postconcussive, psychiatric, and neuropsychological factors in 390 Veterans (86% with mild TBI) to determine what factors were associated with employment or enrolment in postsecondary education. Bivariate correlations and multivariate regression were used. MAIN OUTCOMES AND RESULTS: age, minority status, and service connected disability ratings were significantly associated with employment and postsecondary education enrolment in a multivariate context, whereas TBI-related factors and neurocognitive, postconcussive, and psychiatric symptom severity were not associated with employment or postsecondary education outcomes. CONCLUSIONS: Further research is needed to confirm these findings and to evaluate the contribution of age, minority status, and disability on successful return to work and/or school for Veterans with a history of TBI.

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer's Disease.

There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer's disease (AD), perhaps even before amyloid-ß accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.

Follow the liar: the effects of adult lies on children's honesty.

Recent research shows that most adults admit they lie to children. We also know that children learn through modeling and imitation. To date there are no published studies that examine whether lying to children has an effect on children's honesty. We aimed to bridge the gap in this literature by examining the effects of adults' lies on elementary and preschool-aged children's behavior using a modified temptation resistance paradigm, in which children are tempted to peek at a toy they have been told not to look at, and later given a chance to either admit peeking, or try to conceal their transgression by lying. Prior to being tested, half of the children were told a lie and half were not. We then measured both cheating (peeking) and lie-telling behaviors. We hypothesized that lying to a child would increase the likelihood that they would both peek at the toy and lie about having done so. Results showed that school-age children were more likely to peek if they had been lied to, and were also more likely to lie about peeking. In contrast with the school-age children, there was no difference in peeking or lying for preschoolers who were and were not lied to. These results have important implications for parenting and educational settings.

How the forebrain transitions to adulthood: developmental plasticity markers in a long-lived rodent reveal region diversity and the uniqueness of adolescence.

Maturation of the forebrain involves transitions from higher to lower levels of synaptic plasticity. The timecourse of these changes likely differs between regions, with the stabilization of some networks scaffolding the development of others. To gain better insight into neuroplasticity changes associated with maturation to adulthood, we examined the distribution of two molecular markers for developmental plasticity. We conducted the examination on male and female degus (Octodon degus), a rodent species with a relatively long developmental timecourse that offers a promising model for studying both development and age-related neuropathology. Immunofluorescent staining was used to measure perineuronal nets (PNNs), an extracellular matrix structure that emerges during the closure of critical plasticity periods, as well as microglia, resident immune cells that play a crucial role in synapse remodeling during development. PNNs (putatively restricting plasticity) were found to be higher in non-juvenile (>3 month) degus, while levels of microglia (putatively mediating plasticity) decreased across ages more gradually, and with varying timecourses between regions. Degus also showed notable variation in PNN levels between cortical layers and hippocampal subdivisions that have not been previously reported in other species. These results offer a glimpse into neuroplasticity changes occurring during degu maturation and highlight adolescence as a unique phase of neuroplasticity, in which PNNs have been established but microglia remain relatively high.

Cognitive control regions are recruited in bilinguals' silent reading of mixed-language paragraphs.

When switching languages, bilinguals recruit a language control network that overlaps with brain regions known to support general cognitive control, but it is unclear whether these same regions are recruited in passive comprehension of language switches. Using fMRI with a blocked design, 24 Spanish-English bilinguals silently read 36 paragraphs in which the default language was Spanish or English, and that had either (1) no switches, (2) function word switches or (3) content word switches. Relative to no switches, function switches activated the right IFG, bilateral MFG, and left IPL/SMG. In contrast, switching on content words produced limited neural switching costs observed only in the left IFG. Switching into the dominant language was more costly in the right SMG than switching into the nondominant language, and neural switching costs were correlated with switching costs in the dominant language in cued picture-naming. Seemingly passive reading comprehension involves brain regions known to support cognitive control in active switching during production, possibly reflecting the operation of a modality-general switch mechanism.

Anterior Cingulate Structure and Perfusion is Associated with Cerebrospinal Fluid Tau among Cognitively Normal Older Adult APOEɛ4 Carriers.

Evidence suggests the ɛ4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (ɛ4+, ɛ4-) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in ɛ4+, whereas these relationships were not evident in ɛ4-. In the rACC, higher CSF tau was associated with higher CTH for both ɛ4+ and ɛ4-, and with lower CBF only in ɛ4+. Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer's disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in ɛ4+ and a positive relationship in ɛ4-. Findings suggest the presence of an ɛ4-related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition.

Neurobehavioral symptom validity and performance validity in veterans: Evidence for distinct outcomes across data types.

Self-reported traumatic brain injury (TBI) is common in combat veterans, and identification of psychiatric and neuropsychological consequences following TBI has become a priority for veteran healthcare. Given the importance of accurately capturing symptoms potentially related to TBI in VA settings, validity metrics are frequently used to evaluate both neuropsychological testing validity and the validity of symptom self-reports. The Validity-10 of the Neurobehavioral Symptom Inventory is one such metric that was designed to evaluate symptom over-reporting and thus identify individuals who may produce inconclusive testing profiles. However, the Validity-10's ability to predict objective effort during neuropsychological testing has not been sufficiently explored in veterans. Clinical evaluation data were collected from 295 veterans seeking treatment in a VA TBI clinic. We examined whether the Validity-10 can predict invalid performance on a battery of neuropsychological tests. Validity-10 was a poor predictor of performance validity metrics. Results provide a conceptual replication of earlier work demonstrating that performance and symptom validity are divergent. As such, separate evaluation of these domains is warranted during evaluations conducted in veteran TBI populations.

Interaction of APOE, cerebral blood flow, and cortical thickness in the entorhinal cortex predicts memory decline.

The ε4 allele of the apolipoprotein E (APOE) gene, a risk factor for cognitive decline, is associated with alterations in medial temporal lobe (MTL) structure and function, yet little research has been dedicated to understanding how these alterations might interact to negatively impact cognition. To bridge this gap, the present study employed linear regression models to determine the extent to which APOE genotype (ε4+, ε4-) modifies interactive effects of baseline arterial spin labeling MRI-measured cerebral blood flow (CBF) and FreeSurfer-derived cortical thickness/volume (CT/Vo) in two MTL regions of interest (entorhinal cortex, hippocampus) on memory change in 98 older adults who were cognitively normal at baseline. Baseline entorhinal CBF was positively associated with memory change, but only among ε4 carriers with lower entorhinal CT. Similarly, baseline entorhinal CT was positively associated with memory change, but only among ε4 carriers with lower entorhinal CBF. Findings suggest that APOE ε4 carriers may experience concomitant alterations in neurovascular function and morphology in the MTL that interact to negatively affect cognition prior to the onset of overt clinical symptoms. Results also suggest the presence of distinct multimodal neural signatures in the entorhinal cortex that may signal relative risk for cognitive decline among this group, perhaps reflecting different stages of cerebrovascular compensation (early effective vs. later ineffective).

Dose-dependent association of accelerometer-measured physical activity and sedentary time with brain perfusion in aging.

INTRODUCTION: Age-related decreases in cerebral blood flow (CBF) may lead to cognitive decline, while physical activity (PA) can maintain CBF and cognition in aging. The intensity of PA needed to affect CBF in aging, and the independent effects of sedentary time on CBF are currently unknown. Moreover, research conducted in free-living environments with objective measures of PA (e.g., accelerometry) is lacking. METHODS: This cross-sectional study used accelerometry to objectively measure sedentary time, all light PA [AllLightPA], moderate-to-vigorous PA [MVPA], and total activity counts [TAC] in 52 cognitively healthy older adults. Robust linear regressions investigated the association of CBF (using arterial spin labeling magnetic resonance imaging) in frontal and medial temporal regions, with each PA intensity and sedentary time. RESULTS: Greater sedentary time was significantly associated with lower CBF in lateral and medial frontal regions after adjusting for MVPA, while higher AllLightPA (adjusted for MVPA), MVPA (adjusted for AllLightPA), and TAC were associated with greater CBF in lateral and medial frontal regions. DISCUSSION: Lighter activities, as well as MVPA, are beneficial to CBF in brain regions typically affected by the aging process and malleable to exercise interventions (i.e., the frontal lobes), whereas sedentary time is an independent risk factor for neurovascular dysregulation in normal aging.

Neurocognition, psychiatric symptoms, and lifetime homelessness among veterans with a history of traumatic brain injury.

We retrospectively investigated archival clinical data, including correlates of lifetime homelessness, in 503 Veterans with a history of traumatic brain injuries (86.5% mild) who completed neuropsychological evaluations and passed performance validity tests. The 471 never-homeless and 32 ever-homeless Veterans were compared on demographic factors, TBI severity, psychiatric diagnosis, subjective symptoms, and neuropsychological functioning. Homelessness history was significantly associated with unemployment, lower disability income, more severe depressive, anxiety, posttraumatic stress disorder, and postconcussive symptoms, and lower performances on two of fifteen neurocognitive tests. In a multiple logistic regression model, current unemployment and substance use disorder remained significantly associated with lifetime homelessness.

The potential of calibrated fMRI in the understanding of stress in eating disorders.

Eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED), are medically dangerous psychiatric disorders of unknown etiology. Accumulating evidence supports a biopsychosocial model that includes genetic heritability, neurobiological vulnerability, and psychosocial factors, such as stress, in the development and maintenance of ED. Notably, stress hormones influence appetite and eating, and dysfunction of the physiological stress response has been implicated in ED pathophysiology. Stress signals also appear associated with food reward neurocircuitry response in ED, providing a possible mechanism for the role of stress in appetite dysregulation. This paper provides a review of some of the interacting psychological, behavioral, physiological, and neurobiological mechanisms involved in the stress response among individuals with ED, and discusses novel neuroimaging techniques to address potential physiological confounds of studying neural correlates of stress in ED, such as calibrated fMRI.

Temporal gradient during famous face naming is associated with lower cerebral blood flow and gray matter volume in aging.

OBJECTIVE: Evidence suggests that famous face naming may be a cognitive ability especially sensitive to the early pathological processes of Alzheimer's disease (AD) and that those at risk for AD may demonstrate a Ribot temporal gradient (RTG), characterized by better performance for naming remote famous faces than for naming recent famous faces. Reductions in cerebral blood flow (CBF) and gray matter volume (GMV) have been implicated in the neuropathological cascade of AD and show utility as biomarkers of AD risk. We examined whether a RTG during famous face naming was associated with lower CBF and/or GMV among a group of cognitively normal older adults. METHODS: Voxel-wise independent samples t-tests were employed to contrast resting CBF values between those who exhibited a RTG (RTG+) during a famous face naming task and those who did not (RTG-) among a sample of 52 cognitively normal older adults (25 RTG-, 27 RTG+; mean age = 73). Groups were also compared on GMV using a voxel-wise general linear model. RESULTS: Significant group differences in CBF and GMV were found, whereby the RTG+ group demonstrated reduced CBF and GMV within medial temporal lobe regions (hippocampus, parahippocampal gyrus), relative to the RTG- group. CONCLUSIONS: This represents the first study to show that cognitively intact older adults who demonstrate a RTG during famous face naming exhibit vascular dysregulation and structural changes similar to that seen in AD risk. Findings suggest that famous face naming ability may be particularly sensitive to the very early brain changes associated with AD.

Multivariate assessment of subjective and objective measures of social and family satisfaction in Veterans with history of traumatic brain injury.

Approximately 20% of current-era Veterans have sustained a traumatic brain injury (TBI), which can result in persistent postconcussive symptoms. These symptoms may disrupt family and social functioning. We explored psychiatric, postconcussive, and cognitive factors as correlates of objective functioning and subjective satisfaction in family and social relationships. At entry into a supported employment study, 50 unemployed Veterans with a history of mild to moderate TBI and current cognitive impairment were administered baseline assessments. Multivariate stepwise regressions determined that higher levels of depressive symptomatology were strongly associated with less frequent social contact, as well as lower subjective satisfaction with family and social relationships. Worse verbal fluency predicted less frequent social contact, whereas worse processing speed and switching predicted higher levels of subjective satisfaction with family relationships. The pattern of results remained similar when examining those Veterans with only mild TBI. Depressive symptoms and cognitive functioning may impact Veterans' social contact and satisfaction with family and social relationships. Evidence-based interventions addressing depression and cognition may therefore aid in improving community reintegration and satisfaction with social and family relationships.

Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.

Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.

Postconcussive symptom overreporting in Iraq/Afghanistan Veterans with mild traumatic brain injury.

A comprehensive evaluation, including the assessment of neurobehavioral symptoms, has been instituted at the Department of Veterans Affairs (VA) healthcare system to address the large number of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans returning with mild traumatic brain injuries (mTBIs). The Validity-10 is measure of symptom overreporting embedded within the Neurobehavioral Symptom Inventory, a component of the comprehensive evaluation that assesses postconcussive symptom severity. The Validity-10 is composed of 10 unlikely/low-frequency items and a validated cutoff score to identify postconcussive symptom overreporting. We examined the items and cutoff used in the initial development and validation study of the Validity-10 through retrospective chart reviews of 331 treatment-seeking Veterans who sustained an mTBI. The Validity-10 exhibited significant relationships with psychiatric variables, VA service connection, and neuropsychological performance validity (all p < 0.01), but nonsignificant relationships with demographic and injury variables (all p > 0.05). Furthermore, the Validity-10 modestly predicted neuropsychological performance validity test failure over and above psychiatric comorbidities and VA service connection. The present study supports the use of the Validity-10 to assess symptom validity in treatment-seeking OIF/OEF Veterans with a history of mTBI.