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Despite considerable research documenting how stress affects brain and neurobehavioral outcomes, few studies have assessed stressor exposure occurring over the entire life span, and no studies have investigated these associations in people living with HIV (PLWH), despite the high stress and disease burden experienced by this population. To address this issue, we examined how cumulative lifetime chronic stressor exposure related to cognition and brain integrity (i.e., gray matter volume) in White and African American PLWH and HIV-uninfected (HIV-) adults.Participants were 91 community-dwelling adults (47.3% PLWH) who completed a comprehensive interview assessing lifetime stressor exposure using the Stress and Adversity Inventory and underwent neuropsychological testing and structural magnetic resonance imaging. Regional brain volumes were derived from T1-weighted images processed through Freesurfer.As hypothesized, greater lifetime chronic stressor exposure was related to worse global cognition ( b = -0.06, standard error [SE] = 0.03, p = .032), processing speed ( b = -0.04, SE = 0.14, p = .041), and executive functioning ( b = -0.06, SE = 0.02, p = .02), and smaller prefrontal cortex (PFC) volume ( b = -16.20, SE = 5.78, p = .007). HIV status did not moderate any of these associations. Moreover, results from mediation analyses demonstrated that the relationship between lifetime chronic stressor exposure and processing speed was fully mediated by PFC volume.These results highlight the critical role of the PFC in the maintenance of processing speed abilities and its vulnerability to cumulative stressor exposure. Specifically, the negative impact of lifetime chronic stressor exposure on cognition-particularly functions reliant on frontal lobe integrity-may be partly driven by smaller volumes in the PFC.

OBJECTIVE: The present study investigated the contribution of health risk factors (using the Charlson Comorbidity Index [CCI]) on cognitive outcomes in a sample of 380 HIV-positive (HIV+; n = 221) and HIV-seronegative (HIV−; n = 159) African American and European American adults aged 50+. METHODS: Participants were recruited from HIV clinics and community advertisements. HIV status was confirmed by serological testing. Self-report and chart history review was used to gather information about medical sss-comorbidities. The Charlson Comorbidity Index (CCI) was used to create a comorbidity score. Participants were administered a brief cognitive test battery. RESULTS: As expected, health risks were greater among those with HIV. There was a HIV × Race interaction on CCI scores, such that in the HIV + group, European Americans had significantly higher CCI scores (M = 3.74; SD = 2.1) than African American HIV + participants (M = 2.70; SD = 1.9). However, in the HIV − group, African Americans had significantly higher CCI scores (M = 2.20; SD = 1.1) than HIV − European American participants (M = 1.80; SD = 1.2). Also, consistent with hypotheses, across the entire sample CCI score was significantly associated with global cognition (β = −.24, p = .02). CONCLUSIONS: Study results underscore the importance of considering HIV serostatus in studies examining racial disparities in health, and how multiple medical risks relate to cognitive outcomes. Neuropsychologists evaluating patients living with HIV should consider how the presence of multiple medical comorbidities may contribute to the course of cognitive decline as people age.

Objective This cross-sectional study examined the effects of socioeconomic status (SES) mobility from childhood to adulthood on psychological and cognitive well-being in African American and non-Hispanic White HIV-positive (HIV+) and HIV-seronegative (HIV-) adults who are part of an ongoing study investigating psychosocial and neurobehavioral effects of HIV. Methods Participants (N = 174, 24.1% female, 59.2% African American, 67.8% HIV+) were categorized into four groups (upward mobility, downward mobility, stable-not-poor, chronic-poverty) based on self-reported childhood and current community SES (which were correlated with objective measures of SES and proxies of childhood SES). SES groups were compared on self-report measures of psychological well-being, subjective executive functioning ratings, and performance across six cognitive domains. Primary analyses were stratified by HIV status. Results For the HIV+ group, SES mobility was associated with psychological well-being (chronic burden of stress: F(7,101) = 3.17, mean squared error [MSE] = 49.42, p = .030, η2 = 0.14; depressive symptoms: F(7,101) = 4.46, MSE = 70.49, p = .006,η2 = 0.14), subjective ratings of executive dysfunction (F(7,101) = 6.11, MSE = 114.29, p = .001,η2 = 0.18), and objective performance in executive functioning (F(9,99) = 3.22, MSE = 249.52, p = .030, η2 = 0.15) and learning (F(9,99) = 3.01, MSE = 220.52, p = .034, η2 = 0.13). In the control group, SES mobility was associated with chronic stress burden (F(5,49) = 4.677, p = .025, η2 = 0.15); however, no other relationships between SES mobility and outcomes of interest were observed (all p values > .20). In general, downward mobility and chronic poverty were associated with worse ratings across psychological well-being measures and cognitive performance. Conclusions Findings within the HIV+ group are consistent with previous studies that report downward mobility to be associated with poor psychological outcomes. People living with HIV may be particularly vulnerable to the adverse effects of socioeconomic instability.

Objective: Memory problems are a frequent complaint in neuropsychological settings, particularly among individuals in mid-to-late adulthood and those who have experienced neurological insult (e.g., head trauma; Bay et al., 2012; Lezak et al., 2004; Wammes et al., 2017). Neuropsychiatric comorbidities that influence cognitive functioning (e.g., depression, anxiety, posttraumatic stress) are also common among neuropsychological patients, which can challenge interpreting etiology and predicting prognosis (Campbell et al., 2009; Reischies & Neu, 2000). Prolonged trauma exposure is associated with brain abnormalities in regions that subserve memory and executive functions (Daniels et al., 2016; Woon et al., 2010). Furthermore, a subgroup of individuals with trauma exposure experience dissociative symptoms, which can also interfere with memory and performing goal-directed behaviors (Bergouignan et al., 2014; Brewin et al., 2013; Ozdemir et al., 2015). Method: In this article, we focus on symptoms that are consistent with dissociation and present three case studies of trauma-exposed women who were referred for neuropsychological testing following complaints of memory decline. Results: Formal neuropsychological testing did not fully support the degree of amnestic symptoms reported. Based upon the complex pattern of results, we propose a potential hypothesis for consideration: the dissociative interference hypothesis. Conclusions: For all three women presented, dissociation was a common symptom that may have contributed to an exacerbation of memory failures and amnestic experiences. Thus, interventions targeted at increasing awareness, rather than withdrawal, during times of stress may lead to a reduction in their memory complaints. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The acceptance of racist practices in psychological assessment, like the use of racist stimuli in testing material, has gone unchallenged for far too long. Such practices are emblematic of the entrenched systems of structural racism and pernicious presence of anti-Black oppression within psychology and beyond. This article brings into focus one glaring example: the inclusion of a noose as an item in one of the most widely used standardized tests in neuropsychology-the Boston Naming Test. The deeply offensive nature of this item has gone publicly unaddressed in the psychological literature for decades despite over 27,000 published articles with this test as a primary keyword. Herein, we review the history of the racialized weaponization of the noose in the United States; the potential psychological harm and test performance degradation imposed by including racist stimuli in assessment materials; and the ethical and cultural competency implications of exposing examinees to racist stimuli during psychological assessments. Finally, we call out the professional complicity underlying this item's persistence in psychology, urging psychologists, test publishers, and members of editorial boards to put an end to the complicit support and take clear corrective action in response to this offense. We also charge our colleagues and community to critically review other psychological assessment measures, language, and procedures in their respective subdisciplines to make the changes that will align professional practice with the antiracist values required to undo the effects of structural racism in psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

BackgroundHuman immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure.MethodsData were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance.FindingsLower current CD4+ count was associated with smaller hippocampal (β= 20.3 mm3per 100 cells/mm3;p= 0.0001) and thalamic volumes (β= 29.3;p= 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes (β= 65.1;p= 0.0009). On average, a dVL was associated with smaller hippocampal (Cohen’sd= 0.24;p= 0.0003) and amygdala volumes (d= 0.18;p= 0.0058).InterpretationIn HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health.FundingThis work was supported, in part, by NIH grant U54 EB020403.Research in ContextEvidence before this studyHIV type-1 infection can be managed with antiretroviral therapy, however neurocognitive impairment persists even in treated HIV+ individuals. Given the challenges associated with standardized cognitive testing, there is a need to identify quantitative markers of central nervous system impairment. A number of neuroimaging studies have reported brain abnormalities in HIV-infected patients; however, prior studies investigating associations between CD4+ T-cell count or HIV viral load and subcortical brain volume report variable effect sizes and regional distributions of effects, limiting the generalizability of the conclusions drawn to date. We have conducted a literature search for reports in English language journals published until June 2019, using the following search terms: HIV AND subcortical AND neuroimaging AND brain AND viral load AND RNA AND CD4. After removing studies that were not applicable, there were 30 studies investigating CD4+ T-cell count and viral load associations with subcortical brain structure.Added value of the studyThe aim of the current study was to investigate structural brain associations with two biomarkers universally used to monitor immune function and treatment response, namely plasma RNA viral load and CD4+ T-cell counts. Prior analyses have been performed in smaller, heterogeneous cohorts, but by combining data across cohorts, we can identify consistent associations between brain volume and indicators of HIV infection across cohorts. The ENIGMA-HIV Working Group was established to identify common neurobiological signatures of the HIV-infected brain by harmonizing data analysis from HIV neuroimaging studies worldwide. The value of this dataset is that it is well-powered and representative of many HIV+ people living in the cART era.Implications of all the available evidenceOur results provide robust evidence that despite demographic and clinical heterogeneity among HIV-infected individuals, brain abnormalities are consistently linked to HIV viral load and immunosuppression. This supports the importance of achieving viral suppression and immune system restoration in maintaining brain health in people living with HIV. The vulnerability of limbic regions, found in this study, extends beyond the classically implicated regions of the basal ganglia; this suggests that these regions remain an important target of cART era HIV research, especially given their heightened vulnerability to age-associated atrophy and neurodegeneration.

Key Points Question Are HIV plasma markers that are universally used to monitor immune function and treatment response associated with subcortical brain volumes in clinically and demographically heterogeneous HIV-infected individuals? Findings In this cross-sectional study of 1203 HIV-infected adults, lower current CD4+ T-cell counts were associated with smaller hippocampal and thalamic volumes independent of treatment status, although in the subset of participants not receiving treatment, they were associated with smaller putamen volumes. Across all participants, detectable viral load was associated with smaller hippocampal volumes, but in the subset of participants receiving HIV treatment, detectable viral load was also associated with smaller amygdala volumes. Meaning In a heterogeneous population of HIV-infected individuals, volumes of structures in the limbic system were consistently associated with plasma markers., Importance Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P, This cross-sectional study examines structural brain associations with CD4+ T-cell count and viral load in HIV-positive individuals taking and not taking combination antiretroviral therapy.

BackgroundYouth living with HIV (YLHIV) in Sub-Saharan African (SSA) are less likely to adhere to antiretroviral therapy (ART) and other health-related regimens. As a consequence, YLHIV are not only at risk for health problems and mental health comorbidities, but are also at risk for cognitive deficits, including in areas of memory and executive functioning. The Suubi+Adherence study followed 702 adolescents (10-16 years of age) receiving bolstered standard of care and a family economic empowerment intervention comprising an incentivized youth financial savings account (YSA) augmented with financial literacy training (FLT) and peer mentorship. The study findings pointed to superior short-term viral suppression and positive adolescent health and mental health functioning among participants receiving the intervention. The original group of adolescents who received Suubi+Adherence are now transitioning into young adulthood. This paper presents a protocol for the follow-up phase titled Suubi+Adherence Round 2.MethodsThe original cohort in Suubi+Adherence will be tracked for an additional five years (2020-2025). Specifically, the long term follow-up will allow to: 1) ascertain the extent to which the short term outcomes identified in the first 6 years of the intervention are maintained as the same group transitions through young adulthood; and 2) address new scientific questions regarding ART adherence; HIV care engagement; protective health behaviors; and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. Additionally, the team examines the potential mechanisms through which the observed long-term outcomes happen. Moreover, the Suubi+Adherence-Round 2 adds a qualitative component and extends the cost effectiveness component.DiscussionGuided by asset and human development theories, Suubi+Adherence-R2 will build on the recently concluded Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA as they transition into young adulthood. The study will address new scientific questions regarding long-term ART adherence, HIV care engagement, protective health behaviors, and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. The findings may inform efforts to improve HIV care among Uganda’s YLHIV, with potential replicability in other low-resource countries.Trial registrationClinicalTrials.gov, ID:NCT01790373

Objectives:Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era.Methods:For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis (N = 11 studies) was performed and included data from 2139 PLWH.Results:In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables (p = .017). Analyses of individual VRFs demonstrated type 2 diabetes (p = .004), hyperlipidemia (p = .043), current smoking (p = .037), and previous CVD (p = .0005) were significantly associated with global neurocognitive impairment.Conclusions:VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.

Objectives: People living with HIV (PLWH) are more likely to report sleep difficulties and cognitive deficits. While cognitive impairment associated with sleep problems have been found in healthy and medical populations, less is known about the effects of poor sleep health (SH) on cognition among PLWH. This study examined differences in cognitive performance among participants classified based upon their HIV status and reported SH. Methods: One hundred sixteen (N=116) adults recruited from the Greater Los Angeles community were administered a comprehensive cognitive test battery and completed a questionnaire about SH. Participants were classified into the following HIV/SH groups: [HIV+/good sleep health (SH+; n=34); HIV−/SH+ (n=32); HIV−/poor sleep health (SH−; n=18) and HIV+/SH− (n=32)]. Results: For both HIV+ and HIV− individuals, poor SH was associated with lower cognitive performance, with the domains of learning and memory driving the overall relationship. The HIV+/SH− group had poorer scores in domains of learning and memory compared to the SH+ groups. Additionally, the HIV−/SH− group demonstrated poorer learning compared to the HIV−/SH+ group. Conclusions: Our findings suggest that sleep problems within medical populations are relevant to cognitive functioning, highlighting the clinical and scientific importance of monitoring sleep health and cognition to help identify individuals at greatest risk of poor health outcomes. Longitudinal investigations using both objective and subjective measures of sleep are needed to determine the robustness of the current findings and the enduring effects of poor SH in the context of chronic disease. (JINS, 2018, 24, 1038–1046)

The purpose of the current study was to examine the independent and interactive effects of social adversity (SA) and HIV infection on subcortical shape alterations and cognitive functions. Participants included HIV+ (n=70) and HIV- (n=23) individuals who underwent MRI, neurocognitive and clinical assessment, in addition to completing questionnaires from which responses were used to create an SA score. Bilateral amygdalae and hippocampi were extracted from T1-weighted images. Parametric statistical analyses were used to compare the radial distance of the structure surface to a median curve to determine the presence of localized shape differences as a function of HIV, SA and their interaction. Next, multiple regression was used to examine the interactive association between HIV and SA with cognitive performance data. An HIV*SA interactive effect was found on the shape of the right amygdala and left hippocampus. Specifically, HIV-infected participants (but not HIV-uninfected controls) who evidenced higher levels of SA displayed an inward deformation of the surface consistent with reduced volume of these structures. We found interactive effects of HIV and SA on learning/memory performance. These results suggest that HIV+ individuals may be more vulnerable to neurological and cognitive changes in the hippocampus and amygdala as a function of SA than HIV- individuals, and that SA indicators of childhood SES and perceived racial discrimination are important components of adversity that are associated with cognitive performance.

Background The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV + ) and HIV-negative (HIV–) individuals. Methods Participants (HIV+, n = 48; HIV–, n = 29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.

Racial disparities in health outcomes between African Americans and European Americans have been well-documented, but not fully understood. Chronic inflammation contributes to several of the diseases showing racial disparities (e.g., Human Immunodeficiency Virus [HIV]), and racial differences in stress exposure (e.g., experiences of racial discrimination) that stimulate pro-inflammatory processes that may contribute to differential health outcomes. We performed a cross-sectional bioinformatic analyses relating perceived discrimination (as measured by the Perceived Ethnic Discrimination Questionnaire [PED-Q]) to the activity of pro-inflammatory, neuroendocrine, and antiviral transcription control pathways relevant to the conserved transcriptional response to adversity (CTRA) in peripheral blood leukocytes. Subjects were 71 individuals (37 HIV-seropositive (HIV+); 34 HIV-seronegative (HIV-)) (mean age = 53 years, range 27-63), who self-identified either as African American/Black (n = 48) or European American/White (n = 23). This provided the opportunity to examine the independent effects of race and HIV, as well as the modifying role of perceived discrimination on pathways involved in CTRA. Exploratory analysis examined the interactive effects of HIV and race on pathways involved in CTRA. Relative to European Americans, African Americans showed increased activity of two key pro-inflammatory transcription control pathways (NF- кB and AP-1) and two stress-responsive signaling pathways (CREB and glucocorticoid receptor); these effects did not differ significantly as a function of HIV infection (HIV x Race interaction, all p > .10). Results suggested that differences in experiences of racial discrimination could potentially account for more than 50% of the total race-related difference in pro-inflammatory transcription factor activity. In sum, differential exposure to racial discrimination may contribute to racial disparities in health outcomes in part by activating threat-related molecular programs that stimulate inflammation and contribute to increased risk of chronic illnesses.

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

Background: Despite more widely accessible combination antiretroviral therapy (cART), the human immunodeficiency virus type-1 (HIV) infection remains a global public health challenge. Even in treated and chronically HIV-infected (HIV+) individuals, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in-vivo may delineate the neuropathological processes underlying these deficits. However, to date, neuroimaging findings are inconsistent. Methods: We established the ENIGMA-HIV Working Group to retrospectively pool and harmonize heterogeneous data from 12 HIV neuroimaging studies across Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1- weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72·4% on cART; 70·3% male; 41·6% with detectable viral load; dVL), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell counts) or dVL. Follow-up analyses stratified data by cART status and sex. Findings: After Bonferroni correction, lower current CD4+ counts were associated with smaller hippocampal (β=20·3 mm3 per 100 cells/mm3; p=0·0001) and thalamic volumes (β=29.3; p=0·003); in participants not on cART, they were associated with smaller putamen volumes (β=65·1; p=0·0009). dVLs were associated with smaller hippocampi (Cohen's d=0·24; p=0·0003) and amygdala (d=0·18; p=0·0058). Interpretation: In a globally representative population of HIV+ individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Deficits in these regions may represent a generalizable brain signature of HIV-infection in the cART era. Our findings support the role of viral suppression and immune restoration in maintaining brain health. Funding Statement: Funding for the ENIGMA Center for Worldwide Medicine Imaging and Genomics was provided by the NIH Big Data to Knowledge Program (BD2K; U54 EB020403). Additional funding for this work was provided by NIH grants R01AG059874 (NJ), R01MH117601 (NJ), T32AG058507 (TMN and CRKC), 5T32MH073526 (CRKC), MH083553 (CHH), MH19535 (CHH), R01HL095135 (KJK), MH095661 (TK), UL1RR033176 (TK), UL1TR000124 (TK), MH19535 (TK), NS080655 (BAN), K01AA025306 (ECP), R01HL095135 (CMS), U54MD007584 (CMS), K23MH095661 (ADT), K23AG032872 (VV), R01NS061696 (VV), K24MH098759 (VV), K01AG050707 (AJW), P01AA019072 (RAC), R01MH074368 (RAC), P30 AI042853 (RAC), and by R01MH085604 (RP). This study was also supported by the SA Medical Research Council (DJS), NHMRC APP568746 and APP1045400 (LAC), and the European Research Council Advanced Grant MedYMA 2011- 291080 (XP). Declaration of Interests: PMT, TMN, NJ, and CRKC received partial research support from Biogen, Inc., for work unrelated to the topic of this manuscript. BKN has received an honorarium from MedLink Neurology. VV has served as a consultant for Merck and ViiV Healthcare in the past 3 years, not related to this work. JA has received honoraria for participating in advisory meetings for ViiV Healthcare, Gilead, Merck, Roche and AbbVie. The remaining authors all declare no conflicts of interest. Ethics Approval Statement: Each study obtained approval from their local ethics committee or institutional review board; participants signed an informed consent form at each participating site.

Author(s): Watson, Caitlin Wei-Ming; Sundermann, Erin E; Hussain, Mariam A; Umlauf, Anya; Thames, April D; Moore, Raeanne C; Letendre, Scott L; Jeste, Dilip V; Morgan, Erin E; Moore, David J | Abstract: ObjectiveThe causes of neurocognitive and everyday functioning impairment among aging people living with HIV (PLWH) are multifactorial. Exposure to stress and trauma can result in neurocognitive deficits via activation of neurological and other biological mechanisms.MethodPLWH (n = 122) and persons without HIV (n = 95), 35-65 years of age, completed four questionnaires that were used to generate a trauma, economic hardship (food insecurity and low socioeconomic status), and stress composite variable (TES). Participants also completed a comprehensive neuropsychological battery and standardized self-reports of activities of daily living (ADLs). We examined the independent and interactive effects of TES and HIV status on neurocognitive performance and ADL declines.ResultsPLWH had more traumatic events, more food insecurity, lower socioeconomic status, and higher perceived stress compared with HIV- individuals (all ps l .0001). Among PLWH, a higher composite TES score was associated with worse executive functioning (p = .02), worse learning (p = .02), worse working memory (p = .02), and more ADL declines (p l .0001), even after controlling for relevant demographic, psychiatric, substance use, and HIV disease covariates. On their own, individual TES components did not predict these outcomes. Conversely, no significant relationships were observed between TES and cognitive domains nor ADL declines among HIV- individuals.ConclusionsA composite score of trauma, economic hardship, and stress was significantly associated with worse neurocognitive performance and functional declines among PLWH. These adverse experiences may contribute to neurocognitive and daily functioning difficulties commonly observed among PLWH. Longitudinal studies are needed to elucidate the relationships between economic/psychosocial adversities and cognitive/functional outcomes over time, and examine potential mediators, such as inflammatory biomarkers. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: Despite more widely accessible combination antiretroviral therapy (cART), the human immunodeficiency virus type-1 (HIV) infection remains a global public health challenge. Even in treated and chronically HIV-infected (HIV+) individuals, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in-vivo may delineate the neuropathological processes underlying these deficits. However, to date, neuroimaging findings are inconsistent. Methods: We established the ENIGMA-HIV Working Group to retrospectively pool and harmonize heterogeneous data from 12 HIV neuroimaging studies across Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1- weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72·4% on cART; 70·3% male; 41·6% with detectable viral load; dVL), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell counts) or dVL. Follow-up analyses stratified data by cART status and sex. Findings: After Bonferroni correction, lower current CD4+ counts were associated with smaller hippocampal (β=20·3 mm3 per 100 cells/mm3; p=0·0001) and thalamic volumes (β=29.3; p=0·003); in participants not on cART, they were associated with smaller putamen volumes (β=65·1; p=0·0009). dVLs were associated with smaller hippocampi (Cohen's d=0·24; p=0·0003) and amygdala (d=0·18; p=0·0058). Interpretation: In a globally representative population of HIV+ individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Deficits in these regions may represent a generalizable brain signature of HIV-infection in the cART-era. Our findings support the role of viral suppression and immune restoration in maintaining brain health. Funding Statement: Funding for the ENIGMA Center for Worldwide Medicine Imaging and Genomics was provided by the NIH Big Data to Knowledge Program (BD2K; U54 EB020403). Additional funding for this work was provided by NIH grants R01AG059874 (NJ), R01MH117601 (NJ), T32AG058507 (TMN and CRKC), 5T32MH073526 (CRKC), MH083553 (CHH), MH19535 (CHH), R01HL095135 (KJK), MH095661 (TK), UL1RR033176 (TK), UL1TR000124 (TK), MH19535 (TK), NS080655 (BAN), K01AA025306 (ECP), R01HL095135 (CMS), U54MD007584 (CMS), K23MH095661 (ADT), K23AG032872 (VV), R01NS061696 (VV), K24MH098759 (VV), K01AG050707 (AJW), P01AA019072 (RAC), R01MH074368 (RAC), P30 AI042853 (RAC), and by R01MH085604 (RP). This study was also supported by the SA Medical Research Council (DJS), NHMRC APP568746 and APP1045400 (LAC), and the European Research Council Advanced Grant MedYMA 2011- 291080 (XP). Declaration of Interests: PMT, TMN, NJ, and CRKC received partial research support from Biogen, Inc., for work unrelated to the topic of this manuscript. BKN has received an honorarium from MedLink Neurology. VV has served as a consultant for Merck and ViiV Healthcare in the past 3 years, not related to this work. JA has received honoraria for participating in advisory meetings for ViiV Healthcare, Gilead, Merck, Roche and AbbVie. The remaining authors all declare no conflicts of interest. Ethics Approval Statement: Each study obtained approval from their local ethics committee or institutional review board; participants signed an informed consent form at each participating site.

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV-seronegative controls. T1-weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

This article seeks to identify factors associated with HIV-transmission-related risk behavior among HIV+ African American men. We examined biological, psychological, cognitive, and social factors and recent HIV-transmission-related risk behavior (i.e., needle sharing, unprotected sex, exchange sex) among a sample of HIV+ African American men. A binary logistic regression showed that individuals under age 50 (OR = 4.2), with clinically-elevated masochism scores (OR = 3.9) on the Millon Clinical Multiaxial Inventory-III (MCMI-III), current substance abuse/dependence (OR = 2.6), and higher sensation-seeking (OR = 1.3) were more likely to report recent risk behavior. We conclude that reducing substance use, addressing self-defeating attitudes, and improving self-control may be avenues for future prevention and intervention research among HIV+ African American men engaging in HIV-transmission-related risk behavior.

Behavioral disorders are common in persons infected with human immunodeficiency virus (HIV). The differential includes preexisting psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection, and the adverse effects of medical therapies. Many patients have more than one contributing or comorbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the coadministration of antiretroviral therapy and the specific neurologic problems common in patients infected with HIV.

Provides an introduction to this special edition of Psychological Trauma. The papers included in this special section focus on aspects of trauma and the effects of trauma in a cultural context that pertains to the way of life in South Africa. These articles highlight the complexities of the effects of trauma and call for tailored interventions to address the lasting effects on health and mental health. (PsycINFO Database Record

Objective Adults aging with HIV face elevated rates of frailty than the general aging population and are frail at younger ages, but associations between frailty and cognition in HIV are not well understood. The study aimed to examine: 1) relationships between frailty index and age, and whether relationships differed by HIV status; 2) relationships between frailty index and cognitive performance, and whether relationships differed by HIV-status. It was hypothesized that 1) the frailty index would significantly predict age in non-infected (HIV-) controls but not HIV-infected (HIV+) adults; 2) higher frailty index scores would significantly predict worse cognitive functioning regardless of HIV-status. Method Participants included 109 (39.4% HIV+) participants aged ≥45 from a community-based sample in Los Angeles. HIV-status groups did not differ by age, education, or race (p’s > .10). Frailty was assessed using a deficit accumulation frailty index (DAFI) composed of 32 age-related health variables. A comprehensive neurocognitive battery was used to examine motor, processing speed, executive functioning, verbal fluency, learning, memory, and global functioning. Multivariate linear regression was used to assess relationships between the DAFI and age and cognitive performance, and HIV-by-frailty interaction. Results DAFI scores were higher in HIV+ adults compared to HIV- controls. The DAFI significantly predicted global, motor, and memory performance (p’s Conclusions Findings highlight that relationships between frailty and cognition may be complicated in patients with chronic health conditions. Frailty may not predict cognitive dysfunction in aging HIV+ adults.

In Los Angeles County, the rates of sexually transmitted infections and diseases among African Americans represent a significant public health disparity. Older African American women are at particular risk as they are more likely to engage in high-risk sexual behaviors and report social isolation and loneliness than their younger counterparts. However, the literature on the relationship between sexual health and mental health in this group is limited. The purpose of this study was to use a community-based participatory research (CBPR) approach to better understand sexual health behaviors and mental health among African American women over 50 years of age who reside in South Los Angeles.This project was divided into two phases. Phase I (January-March 2017) of the project consisted of four dialog/focus groups (N = 45) (ages: 50-80; MWomen reported that they did not feel comfortable discussing sexual practices with their physician, partners, and friends. Most women identified depression, loneliness, and self-esteem issues as reasons for engaging in high-risk sexual behaviors. During Phase II, potential intervention avenues emerged to address issues such as lack of physician-patient communication, lack of community support, and dialogs about sex.The use of CBPR greatly enhanced our knowledge of the core issues surrounding sexual health and mental health among older African American women.

Background There is evidence that regular cannabis use has negative effects on sleep health. Relative to HIV- populations, HIV + individuals consistently report greater sleep impairments. The number of HIV + individuals reporting frequent cannabis use, often to treat sleep issues, has significantly increased recently. It is unknown, however, if HIV status moderates the association between cannabis use and sleep health. The current study, therefore, examines these associations in a sample of HIV + and HIV- adults. Methods HIV + and HIV- (N = 107) individuals completed one laboratory visit. Participants completed a 30-day drug use history questionnaire quantifying consumption of cannabis, cigarettes, and alcohol, and a sleep health questionnaire. To verify substance use and HIV status, participants completed a urine toxicology screening and serology testing. Results HIV + individuals demonstrated lower sleep health than HIV- individuals. Linear regressions indicated that HIV status moderated the association between total 30-day cannabis consumption and sleep health; cannabis consumption was negatively associated with sleep health in HIV-, but not HIV + individuals. This interactive effect was significant after examining cigarette/alcohol use, depression symptoms, and demographic variables as covariates. Conclusions These results corroborate studies demonstrating an inverse relationship between sleep health and cannabis consumption. This study also suggests that factors other than cannabis may be associated with lower sleep health in HIV + individuals. Emerging studies suggest that inflammation may mediate effects of cannabis on HIV infection. Future studies examining this mechanism are warranted to understand cannabis further and sleep in HIV + individuals.

ObjectiveHIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear.MethodsHIV+ (n=70) and HIV-negative (HIV-, n=34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n=765, Cam-CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance.ResultsBAG was significantly higher in the HIV+ group than the HIV-groupF(1, 103) = 12.408, p = 0.001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2= 0.29, F(7, 70) = 2.66, p = 0.021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r = −0.26, p = 0.008; memory: r = −0.21, p = 0.034).ConclusionsHIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.

OBJECTIVES Recent studies suggest that intraindividual variability (IIV) of neuropsychological performance may be sensitive to HIV-associated neurologic compromise. IIV may be particularly dependent upon the integrity of frontal-subcortical systems, and therefore may be a meaningful phenotype in HIV. We examined the relationship between change in IIV and white matter integrity among HIV seropositive (HIV+) and HIV seronegative (HIV-) individuals. METHOD The sample consisted of 38 HIV+ participants and 26 HIV- control participants who underwent neuroimaging and a neuropsychological evaluation at baseline and at 2-year follow-up evaluation. RESULTS Among HIV+ participants, increases in IIV (greater dispersion) were related to lower fractional anisotropy (FA) values in the anterior thalamic radiations (ATR) and the superior longitudinal fasciculus (SLF). Changes in mean-level global cognitive functioning were not significantly related to white matter integrity. Additionally, there was a significant Group × IIV interaction effect in the SLF demonstrating that the relationship between IIV and white matter integrity was specific to HIV. CONCLUSIONS Overall, findings suggest that IIV may be more sensitive, relative to mean-level global cognitive functioning, in the detection of neurologic compromise among HIV+ individuals. (PsycINFO Database Record

Viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. It is questionable as to what extent the central nervous system (CNS) is an immune-privileged organ protected by the blood-brain barrier (BBB). Recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may alter the integrity of the blood-brain barrier, and lead to inflammation, swelling of the brain parenchyma and associated neurological syndromes. Here, we expand upon the recent “gateway theory”, by which viral infection and other immune activation states may disrupt the specialized tight junctions of the BBB endothelium making it permeable to immune cells and factors. The model we outline here builds upon the proposition that this process may actually be initiated by cytokines of the IL-17 family, and recognizing the intimate balance between TH17 and TH9 cytokine profiles systemically. We argue that immune surveillance events, in response to viruses such as the Human Immunodeficiency Virus (HIV), cause a TH17/TH9 induced gateway through blood brain barrier, and thus lead to characteristic neuroimmune pathology. It is possible and even probable that the novel TH17/TH9 induced gateway, which we describe here, opens as a consequence of any state of immune activation and sustained chronic inflammation, whether associated with viral infection or any other cause of peripheral or central neuroinflammation. This view could lead to new, timely and critical patient-centered therapies for patients with neuroimmune pathologies across a variety of etiologies. Abbreviations BBB - blood brain barrier, BDV - Borna disease virus, CARD - caspase activation and recruitment domains, CD - clusters of differentiation, CNS - central nervous system, DAMP - damage-associated molecular patterns, DENV - Dengue virus, EBOV - Ebola virus, ESCRT - endosomal sorting complex required for transport-I, HepC - Hepatitis C virus, HIV - human immunodeficiency virus, IFN - interferon, ILn - interleukin-n, IRF-n - interferon regulatory factor-n, MAVS - mitochondrial antiviral-signaling, MBGV - Marburg virus, M-CSF - macrophage colony-stimulating factor, MCP-1 - monocyte chemotactic protein 1 (aka CCL2), MHC - major histocompatibility complex, MIP-α β - macrophage inflammatory protein-1 α β (aka CCL3 & CCL4), MIF - macrophage migration inhibitory factor, NVE - Nipah virus encephalitis, NK - natural killer cell, NLR - NLR, NOD - like receptor, NOD - nucleotide oligomerization domain, PAMP - pathogen-associated molecular patterns, PtdIns - phosphoinositides, PV - Poliovirus, RIG-I - retinoic acid-inducible gene I, RIP - Receptor-interacting protein (RIP) kinase, RLR - RIG-I-like receptor, sICAM1 - soluble intracellular adhesion molecule 1, STAT-3 - signal tranducer and activator of transcription-3, sVCAM1 - soluble vascular cell adhesion molecule 1, TANK - TRAF family member-associated NF- . B activator, TBK1 - TANK-binding kinase 1, TLR - Toll-like receptor, TNF - tumor necrosis factor, TNFR - TNF receptor, TNFRSF21 - tumor necrosis factor receptor superfamily member 21, TRADD TNFR-SF1A - associated via death domain, TRAF TNFR - associated factor, Tregs - regulatory T cellsubpopulation (CD4/8+CD25+FoxP3+), VHF - viral hemorrhagic fever.

UnlabelledDengue, a leading cause of illness and death in the tropics and subtropics since the 1950׳s, is fast spreading in the Western hemisphere. Over 30% of the world׳s population is at risk for the mosquitoes that transmit any one of four related Dengue viruses (DENV). Infection induces lifetime protection to a particular serotype, but successive exposure to a different DENV increases the likelihood of severe form of dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Prompt supportive treatment lowers the risk of developing the severe spectrum of Dengue-associated physiopathology. Vaccines are not available, and the most effective protective measure is to prevent mosquito bites. Here, we discuss selected aspects of the syndemic nature of Dengue, including its potential for pathologies of the central nervous system (CNS). We examine the fundamental mechanisms of cell-mediated and humoral immunity to viral infection in general, and the specific implications of these processes in the regulatory control of DENV infection, including DENV evasion from immune surveillance. In line with the emerging model of translational science in health care, which integrates translational research (viz., going from the patient to the bench and back to the patient) and translational effectiveness (viz., integrating and utilizing the best available evidence in clinical settings), we examine novel and timely evidence-based revisions of clinical practice guidelines critical in optimizing the management of DENV infection and Dengue pathologies. We examine the role of tele-medicine and stakeholder engagement in the contemporary model of patient centered, effectiveness-focused and evidence-based health care.AbbreviationsBBB - blood-brain barrier, CNS - central nervous system, DAMP - damage-associated molecular patterns, DENV - dengue virus, DF - dengue fever, DHF - dengue hemorrhagic fever, DSS - dengue shock syndrome, DALYs - isability adjusted life years, IFN-g - interferon-gamma, ILX - interleukinX, JAK/STAT - janus kinase (JAK) / Signal transducer and activator of transcription (STAT), LT - Escherichia coli heat-labile enterotoxin formulations deficient in GM1 binding by mutation (LT[G33D]), MCP-1 - monocyte chemotactic protein 1, M-CSF - macrophage colony-stimulating fact, MHC - major histocompatibility complex, MIF - macrophage migration inhibitory factor, [MIP-1]-α / -β - macrophage inflammatory protein-1 alpha and beta, mAb - monoclonal antibody, NS1 - non-structural protein 1 of dengue virus, NK - natural killer cells, PAMP - pathogen-associated molecular patterns, PBMC - peripheral blood mononuclear cells, TBF-b - transforming growth factor-beta, TNF-α - tumor necrosis-alpha, VHFs - virus hemorrhagic fevers, WHO - World Health Organization.

OBJECTIVE Somatic symptoms are often reported among victims of trauma, and place a significant burden on primary care health providers. We examined the relationship between lifetime histories of trauma and adversity, including aspects not previously studied (i.e., perceived discrimination), and somatic symptoms, as well as the mediating role of posttraumatic stress symptoms (PTSS) and depressive symptoms. METHOD A multiethnic community sample of 500 male and female participants (230 African American and 270 Latino) completed measures of demographic characteristics, the University of California, Los Angeles Lifetime Adversities Screener (LADS), depressive symptoms, PTSS, and somatic symptoms. RESULTS An ordinary least-squares regression analysis controlling for age, gender, and race/ethnicity indicated that higher levels of lifetime adversity and trauma were significantly associated with more severe somatic symptoms (b = 6.95, p < .0001). Formal mediation tests indicated that there was a significant indirect effect of LADS on somatic symptoms via PTSS and depressive symptoms, indirect effect = 2.64 (95% confidence interval [CI] [1.2, 4.1]) and 2.19 (95% CI [1.3, 3.3]), respectively. Even after PTSS and depressive symptoms were taken into account, the LADS remained significantly associated with somatic symptoms (b = 2.13, p < .05), suggesting partial mediation. CONCLUSION Exposure to traumatic and adverse events (the LADS) was associated with somatic symptom severity. Furthermore, although PTSS and depressive symptoms partially accounted for the association between the LADS and somatic symptoms, the LADS remained significant, suggesting that both exposure to trauma and adversity and the resultant development of PTSS and depressive symptoms influence the development of somatic symptoms. (PsycINFO Database Record

Cumulative evidence suggests that cocaine use could alter the structure and function of different brain systems. However, the extent to which the altered brain structure and function possibly recover over time after cocaine abstinence remains less clear. The present study examines 39 male military veterans with different stages of cocaine addiction and long-term abstinence (from 1 year up to 30 years) and evaluates plausible changes in brain structure and function of specific brain regions that sub-serve addictions. These include the striatum that is involved in cocaine reward; the lateral prefrontal cortex (especially the dorsolateral PFC) that plays a major role in inhibitory control; the insula, which has been implicated in craving; and the medial orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) shown to play key roles in foresight and decision-making. The results suggest that there are differences in both brain structure (gray matter volume, GMV) and function between cocaine USERS and CONTROLS, with USERS showing plausible relative strengthening in neural systems for processing reward and craving, and relative weakening in neural systems involved in inhibitory control and decision-making. Examination of possible neural changes after abstinence suggests that presumed recovery occurs mostly in neural systems related to reward, craving, and inhibitory control, but to a lesser extent in neural systems related to decision-making. Given the limitations of the data in terms of a small sample size, as well as the lack of certainty about occasional use in the abstinent group, these results may be considered as preliminary. However, they are compelling in that they suggest that male military veterans cocaine USERS are indefinitely at a higher risk compared to CONTROLS for making lapses in judgment and decision-making leading to possible relapse, if reward salience and craving become more intense. Understanding the neurobiology of long-term cocaine abstinence in vulnerable populations and beyond could help devising better therapeutic strategies that prevent relapse.

Despite recent advances in treatment, hepatitis C remains a significant public health problem. The hepatitis C virus (HCV) is known to infiltrate the brain, yet findings from studies on associated neurocognitive and neuropathological changes are mixed. Furthermore, it remains unclear if HCV eradication improves HCV-associated neurological compromise. This study examined the longitudinal relationship between neurocognitive and neurophysiologic markers among healthy HCV- controls and HCV+ adults following successful HCV eradication. We hypothesized that neurocognitive outcomes following treatment would be related to both improved cognition and white matter integrity. Participants included 57 HCV+ participants who successfully cleared the virus at the end of treatment (sustained virologic responders [SVRs]) and 22 HCV- controls. Participants underwent neuropsychological testing and, for a nested subset of participants, neuroimaging (diffusion tensor imaging) at baseline and 12 weeks following completion of HCV therapy. Contrary to expectation, group-level longitudinal analyses did not reveal significant improvement in neurocognitive performance in the SVRs compared to the control group. However, a subgroup of SVRs demonstrated a significant improvement in cognition relative to controls, which was related to improved white matter integrity. Indeed, neuroimaging data revealed beneficial effects associated with clearing the virus, particularly in the posterior corona radiata and the superior longitudinal fasciculus. Findings suggest that a subgroup of HCV+ patients experienced improvements in cognitive functioning following eradication of HCV, which appears related to positive changes in white matter integrity. Future research should examine whether any additional improvements in neurocognition and white matter integrity among SVRs occur with longer follow-up periods.

Comorbid psychiatric disorders are common in HIV infection. Mood disorders (e.g., depression) have received the most attention in the literature; however, neuropsychiatric features of apathy and irritability and severe mental illnesses (e.g., schizophrenia, bipolar disorder) have also emerged as important comorbidities that warrant attention. While the former may develop secondary to infection, the latter are believed to place individuals at increased risk for contracting HIV and, once infected, poor HIV-related health outcomes. Psychiatric comorbidities have been linked to a host of adverse functional outcomes, such as increased suicide attempts, drug abuse, and failure to adhere to ARV medications. Differentiating neuropsychiatric features of HIV infection from pre-existing symptoms is particularly important for healthcare providers involved in making diagnostic decisions and treatment recommendations. The following chapter reviews historical and current literature on psychiatric disturbances commonly associated with HIV, with emphasis on assessment. We also provide a brief review of treatments, including non-pharmacological evidence-based treatments.

Objective Large-scale research consortium studies are increasingly used to help aid in early identification of age-related brain changes and neurodegenerative disease risk. Racial/ethnic minorities (REM) are severely underrepresented in publicly available datasets related to neurodegenerative disease. This is problematic given that the US older adult population will be comprised of 40% REM by 2050. As this population grows more diverse, it is crucial that Alzheimer’s disease (AD) risk factors are appropriately characterized and REM are represented in longitudinal research. The purpose of this study was to examine memory, Apolipoprotein E (APOE) status, and hippocampal volume (HV) data among REM participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Participants and Method We sampled 91 Latinx and Non-Hispanic Black (NHB) ADNI participants, which included 41 controls (CN; 39% Latinx) and 50 individuals with mild cognitive impairment (MCI; 52% Latinx). Measures included Logical Memory (LM) Delay, Rey Auditory Verbal Learning Test (RAVLT), Alzheimer’s Disease Assessment Cognitive 13-item Scale (ADAS13), APOE e4 and APOE e2 status, and HV. Groups did not differ by age, education, or memory performance. None of the Latinx sample were e2 carriers, whereas 32% of NHB were e2 carriers. Results For NHB and Latinx MCI groups, LM Delay scores positively predicted greater HV (NHB: R2 = .17, p = .04; Latinx: R2 = .16, p = .04). Better RAVLT performance predicted greater HV for the Latinx MCI group but not for the NHB MCI group (Latinx: R2 = .13, p = .06). For NHB CN, e4 status and ADAS13 were positively correlated (r = .59, p = .002) but negatively correlated for Latinx CN (r = -.58, p = .002). APOE e2 and RAVLT percent forgetting were negatively correlated for NHB MCI (r = -.49, p = .01). Conclusions There appears to be differential risk associated with heterozygous e4 status in Latinx and NHB. APOE e2 may have been protective in the context of e4 in NHB. The degree to which e2 is protective in Latinx is unknown. Results highlight the need for improved REM representation in large-scale studies to understand genetic risk and protective factors in REM.

This study developed and then cross-validated a novel weighting algorithm based on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C, HIV disease severity, cognitive reserve) to predict cognitive functioning among 366 HIV+ adults. The resultant “risk severity score” was used to differentially weight, as a function of age, the impact and magnitude of multiple risk factors on cognition. Among older adults (> 50 years) the risk severity index was differentially predictive of learning/memory and verbal fluency, whereas among younger adults it was linked to working memory and executive function. Cognitive reserve was found to be the most robust predictor of neurocognition.

As the stimulating articles in this Special Issue demonstrate, symptom validity tests (SVTs) are alive and well in neuropsychology and allied fields. At the same time, a number of key unresolved issues regarding the construct validity and clinical utility of SVTs remain. In this commentary, we address six largely unanswered questions regarding SVTs: (1) Do SVTs possess clinical validity?; (2) Is malingering taxonic?; (3) Is there an overarching dimension of malingering and low effort?; (4) How should be combine information from different SVTs?; (5) Can the assessment of psychopathy supplement information from SVTs?; and (6) How do ethnicity and culture affect the interpretation of SVTs? We conclude that SVTs play an indispensable role in the detection of aberrant response sets in neuropsychology, although the precise meaning of scores on many SVTs requires clarification.

© 2015 Elsevier Inc. Background: Deficits in lexical retrieval, present in approximately 40% of HIV. + patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. Objective: We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV. + individuals would demonstrate greater brain activity in frontal-subcortical regions despite minimal differences between groups on neuropsychological testing. Within the HIV. + sample, we examined associations between indices of immunosuppression (recent and nadir CD4. + count) and task-related signal change in frontostriatal structures.Method16 HIV. + participants and 12 HIV. - controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency. Results: HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV. + individuals demonstrating significantly greater activation in BG structures than HIV. - individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV. + group, current CD4. + count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. Conclusion: During phonemic fluency performance, HIV. + patients recruit subcortical structures to a greater degree than HIV. - controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV. + individuals, reduced activity in the frontal-subcortical structures was associated with lower CD4. + count.

Researchers often rely on self-report measures to assess sensitive health-risk behaviors in HIV+ individuals, yet the accuracy of self-report has been questioned, particularly when inquiring about behaviors that may be embarrassing, risky, and/or taboo. We compared an anonymous reporting method—the Unmatched Count Technique (UCT)—to direct self-report in order to assess reporting differences for several health-risk behaviors related to medication adherence and sexual risk. Contrary to hypotheses, the UCT only produced a significantly higher estimated base rate for one sensitive behavior: reporting medication adherence to one's physician, which may have been contextually-primed by our study design. Our results suggest that anonymous reporting methods may not increase disclosure compared to direct self-report when assessing several health-risk behaviors in HIV+ research volunteers. However, our results also suggest that contextual factors should be considered and investigated further, as they may influence perception of sensitive behavior.

© 2016 Informa UK Limited, trading as Taylor & Francis Group. The current study examined the independent and combined effects of HIV and marijuana (MJ) use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. MJ users consisted of individuals who reported regular use of MJ for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n = 55) and HIV- (n = 34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported MJ use. Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV- moderate-to-heavy users (MD= -8.34; 95% CI: -16.11 to -0.56) as well as all other comparison groups. In the domain of verbal fluency, HIV+ light users outperformed HIV- light users (MD= 7.28; 95% CI: 1.62-12.39), but no HIV group differences were observed at other MJ use levels. HIV+ MJ users demonstrated lower viral load (MD= -0.58; 95% CI: -1.30 to 0.14) and higher CD4 count than non-users (MD= 137.67; 95% CI: 9.48-265.85). The current study findings extend the literature by demonstrating the complex relationship between HIV status and MJ use on neurocognitive and clinical outcomes.

Although cognitive impairment has been shown to adversely affect antiviral medication adherence, a subset of cognitively impaired adults nonetheless are able to adequately adhere to their medication regimen. However, little is known about factors that serve as buffers against suboptimal adherence among the cognitively impaired. This study consisted of 160 HIV-positive, cognitively impaired adults (Global Deficit Score ≥ 0.50) whose medication adherence was monitored over 6-months using an electronic monitoring device (MEMS caps). Logistic regressions were run to determine psychosocial variables associated with medication adherence. Higher self-efficacy and treatment related support, a stable medication regimen, stable stress levels, and absence of current stimulant use were predictive of optimal adherence. A distinct array of psychosocial factors was found that buffer against the adverse effects of cognitive impairment on medication adherence. Assessment and interventions targeting these factors may improve adherence rates among cognitively impaired adults.

The Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog) is widely used in AD, but may be less responsive to change when used in people with mild cognitive impairment (MCI). Participants from the Alzheimer’s Disease Neuroimaging Initiative were administered a neuropsychological battery and 1.5 T MRI scans over 2–3 years. Informants were queried regarding functional impairments. Some participants had lumbar punctures to obtain cerebrospinal fluid (CSF). We added executive functioning (EF) and functional ability (FA) items to the ADAS-Cog to generate candidate augmented measures. We calibrated these candidates using baseline data (n = 811) and selected the best candidate that added EF items alone and that added EF and FA items. We selected candidates based on their responsiveness over three years in a training sample of participants with MCI (n = 160). We compared traditional ADAS-Cog scores with the two candidates based on their responsiveness in a validation sample of participants with MCI (n = 234), ability to predict conversion to dementia (n = 394), strength of association with baseline MRI (n = 394) and CSF biomarkers (n = 193). The selected EF candidate added category fluency (ADAS Plus EF), and the selected EF and FA candidate added category fluency, Digit Symbol, Trail Making, and five items from the Functional Assessment Questionnaire (ADAS Plus EF&FA). The ADAS Plus EF& FA performed as well as or better than traditional ADAS-Cog scores. Adding EF and FA items to the ADAS-Cog may improve responsiveness among people with MCI without impairing validity.

Background The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexico-semantic verbal fluency performance among older HIV infected adults. Method 20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted. Results Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume. Conclusions These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function.