The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study.

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 38:1025-1037, 2017. © 2016 Wiley Periodicals, Inc.

Increased subcortical neural activity among HIV+ individuals during a lexical retrieval task.

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.

Comparing the unmatched count technique and direct self-report for sensitive health-risk behaviors in HIV+ adults.

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 (DSR) 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 DSR 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.

Mild test anxiety influences neurocognitive performance among African Americans and European Americans: identifying interfering and facilitating sources.

The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation.

Aging and HIV/AIDS: neurocognitive implications for older HIV-positive Latina/o adults.

In recent years, HIV/AIDS populations have become older and increasingly more ethnically diverse. Concurrently, the prevalence of HIV-related neurocognitive (NC) impairment remains high. This study examined the effects of age and ethnicity on NC function in HIV-positive adults. The sample (N = 126; 84 Latina/o and 42 Non-Hispanic White) completed a comprehensive NC battery. Global NC and domain average demographically-corrected t-scores were generated. There were no significant differences between Younger (<50 years) Latina/os and non-Hispanic Whites on Global NC function or NC domains (all p's >.10), with generally small effect sizes. Older Latina/os (≥50 years) were significantly more impaired than Older Non-Hispanic Whites on processing speed and learning, with trends in Global NC function and memory. Further, effect sizes fell within the medium to large range (Cohen's d's = .49-1.15). This study suggests that older Latina/os are at potentially greater risk for NC impairment, particularly in processing speed and learning, when compared to similarly-aged non-Hispanic whites.

Parental, caregiving, and family leave during clinical neuropsychology postdoctoral training: Recommendations and guidelines from the Women in Neuropsychology (WIN) committee and Education Advisory Committee (EAC) of the Society for Clinical Neuropsychology (SCN; APA division 40).

Objective: Parental and other caregiving leave is important to postdoctoral fellows, yet there is no field-wide recommendation for leave policies among clinical neuropsychology postdoctoral training programs, which is of particular relevance given the two-year requirement for eligibility for board certification. The aims of this manuscript are to (a) discuss general guidelines and recommendations for leave policies, both informed by prior empirical evidence as well as relevant existing policy guidelines from various academic and healthcare organizations, and (b) use vignettes to provide possible solutions for potential leave scenarios. Method: A critical review of literature on family leave from public policy and political science, industrial-organizational psychology, academic medicine, and psychology was conducted and findings were synthesized. Results and Conclusions: Fellowship training programs are encouraged to adopt a competency-based model that permits flexibility in leave during training without necessarily requiring an extended end date. Programs should adopt clear policies and make this information readily available to trainees and think flexibly about training options that best meet the training needs and goals of each individual. We also encourage neuropsychologists at all levels to engage in advocacy for broader systemic supports of trainees seeking equitable family leave.

Effects of stereotype threat, perceived discrimination, and examiner race on neuropsychological performance: simple as black and white?

The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = -.30, 95% confidence interval [CI] [-0.07, -0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = -1.19, 95% CI [-1.78, -.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [-0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups.

Neurocognitive, Sociocultural, and Psychological Factors Impacting Medication Beliefs Among HIV-Seropositive Latinx Adults.

Among Latinx people living with HIV (PLWH), neurocognitive (NC) function, culture, and mental health impact medication adherence. Similarly, health beliefs and attitudes play a role in health care barriers and health behaviors. Research has not examined the effect that compromised neurocognition, sociocultural factors, and mental health have on health beliefs and attitudes. This is especially relevant for Latinx PLWH who are disproportionately impacted by HIV, given that sociocultural factors may uniquely impact HIV-related NC and psychological sequelae. This study investigated the associations between neurocognition, sociocultural factors, mental health, health beliefs, and health attitudes among Latinx HIV-seropositive adults. Within a sample of 100 Latinx PLWH, better verbal learning and executive functioning abilities were associated with more positive attitudes about the benefits of medications and memory for medications. In terms of sociocultural factors, higher English language competence was related to better self-reported memory for medications, and overall, higher US acculturation was associated with more positive attitudes toward health professionals. Depressive symptomatology was negatively associated with attitudes toward medications and health professionals, as well as with self-reported memory for medications. These findings highlight the important interplay between NC, sociocultural, psychological factors, and health beliefs among Latinx PLWH. Adherence intervention strategies and suggestions for dispensing medical information are presented for clinicians and health care practitioners.

HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score.

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed.

The neurocognitive implications of depression and socioeconomic status in people with HIV.

OBJECTIVE: This cross-sectional study investigates the independent and interactive effects of depression and socioeconomic status (SES) on neurocognition in a diverse sample of people with HIV (PWH). METHOD: The sample of 119 PWH (71% Latinx, 27% female) completed comprehensive neurocognitive and psychosocial evaluations and were separated into two groups: those with a history of depression diagnosis (n = 47) and those without (n = 72). RESULTS: The results of regression analyses indicated that lifetime depression was not associated with lower SES nor with worse neurocognitive performance on any neurocognitive outcome. However, a significant main effect of SES was observed on the Hopkins Verbal Learning Test (total), indicating that higher SES was associated with better verbal learning performance (B= .11, SE = .05, p< .02). Lastly, the results revealed an interactive effect of lifetime depression and SES, such that individuals with depression and higher SES performed better on tests of attention/working memory (i.e., WAIS-III Letter-Number Sequencing, B= .08, SE = .04, p< .02; Paced Auditory Serial Addition Test, B= .39, SE = .16, p< .02). CONCLUSIONS: Depression and SES appear to play an important role in the neurocognitive performance of PWH. Specifically, higher SES appears to have a protective effect on attention/working memory among PWH only if they have co-morbid history of lifetime depression.

Disparities in Electronically Monitored Antiretroviral Adherence and Differential Adherence Predictors in Latinx and Non-Latinx White Persons Living with HIV.

Antiretroviral therapy (ART) adherence is vital for optimal HIV treatment. However, there is limited ART adherence research on the US Latinx population, who are at increased risk for HIV infection and worse HIV health outcomes. This study examined electronically measured ART adherence (Medication Event Monitoring System) and its association with demographic, clinical, neurocognitive, and sociocultural variables in Latinx and non-Latinx white (NLW) persons living with HIV [PLWH (N = 128)]. Latinx participants demonstrated worse adherence than NLW participants (p = 0.04). Linear regressions revealed different predictors of adherence. Among Latinx participants, recent cocaine use, stress, and, unexpectedly, higher US acculturation predicted worse adherence (ps < 0.05). Among NLW participants, recent cocaine use predicted worse adherence (p < 0.05). Intergroup comparisons within the Latinx group were not conducted due to subsample size. Thus, ethnicity, sociocultural variables, and cocaine use are important considerations for ART adherence, and poor ART adherence may be one pathway explaining worse outcomes in Latinx PLWH. Culturally tailored adherence interventions incorporating substance use treatment, acculturation, and stress management are warranted to improve health outcomes.

Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism.

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body's efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1-23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health.

Characterization and sociocultural predictors of neuropsychological test performance in HIV+ Hispanic individuals.

Hispanic individuals in the U.S. have been disproportionately impacted by HIV/AIDS, yet little is known regarding the neuropsychological sequelae of HIV within the Hispanic population. This study characterized neuropsychological (NP) test performance of HIV+ English-speaking Hispanic participants (n = 51) and investigated the combined roles of sociocultural factors (e.g., ethnicity, socioeconomic status [SES] proxy, and reading level) on NP test performance among our HIV+ Hispanic and non-Hispanic White participants (n = 49). Results revealed that the pattern of NP impairment in HIV+ Hispanic participants is consistent with the frontal-striatal pattern observed in HIV-associated CNS sequelae, and the overall prevalence of global NP impairment was high compared to previous reports with more ethnically homogeneous, non-Hispanic White cohorts. Multivariate prediction models that considered both sociocultural factors and CD4 count revealed that reading level was the only unique predictor of global NP functioning, learning, and attention/working memory. In contrast, ethnicity was the only unique predictor of abstraction/executive functioning. This study provides support for the use of neuropsychological evaluation in detecting HIV-associated NP impairment among HIV+ Hispanic participants and adds to the growing literature regarding the importance of considering sociocultural factors in the interpretation of NP test performance.

Effects of social adversity and HIV on subcortical shape and neurocognitive function.

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.

Hypothalamic-pituitary-adrenal axis dysregulation and memory impairments in type 2 diabetes.

CONTEXT: There is evidence of both hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the exact nature and the associations between these abnormalities remain unclear. OBJECTIVES: The aim of the study was to characterize the nature of the HPA dysregulation in T2DM and ascertain whether impaired cognition in T2DM could be attributed to these abnormalities. DESIGN: A cross-sectional study was performed, contrasting matched groups on HPA axis function and cognition by using the combined dexamethasone (DEX)/CRH test and a neuropsychological battery assessing declarative and working memory, attention, and executive function. SETTING: The study was conducted in a research clinic in an academic medical center. PARTICIPANTS: Participants were volunteers functioning in the cognitively normal range. We studied 30 middle-aged individuals with T2DM, on average 7.5 yr since diabetes diagnosis, and 30 age-, gender-, and education-matched controls. MAIN OUTCOME MEASURES: Basal cortisol levels, cortisol levels during the DEX/CRH test, and performance on neuropsychological tests were measured. RESULTS: Individuals with T2DM had elevated basal plasma cortisol levels, higher levels after DEX suppression, and a larger response to CRH (all P

HIV-transmission-related risk behavior in HIV+ African American men: Exploring biological, psychological, cognitive, and social factors.

OBJECTIVES: To identify factors associated with HIV-transmission-related risk behavior among HIV+ African American men. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

[Formula: see text]The Relative Utility of Three English Language Dominance Measures in Predicting the Neuropsychological Performance of HIV+ Bilingual Latino/a Adults.

OBJECTIVE: Given the disproportionate impact of neurologic disorders such as HIV on racial/ethnic minorities, neuropsychologists are increasingly evaluating individuals of diverse linguistic backgrounds. This study compares the utility of two brief and one comprehensive language measure to account for variation in English neuropsychological performance within a bilingual population. METHOD: Sixty-two HIV+ English/Spanish bilingual Latino adults completed three language measures in English and Spanish: Self-Reported Language Ability; Verbal Fluency (FAS/PMR); and the Woodcock Munoz Language Survey-Revised (WMLS-R). All participants also completed an English language neuropsychological (NP) battery. RESULTS: It was hypothesized that the comprehensive English/Spanish WMLS-R language dominance index (LDI) would be significantly correlated with NP performance, as well as the best predictor of NP performance over and above the two brief language measures. Contrary to our hypothesis, the WMLS-R LDI was not significantly correlated to NP performance, whereas the easily administered Verbal Fluency and Self-Report LDIs were each correlated with global NP performance and multiple NP domains. After accounting for Verbal Fluency and Self-Report LDI in a multivariate regression predicting NP performance, the WMLS-R LDI did not provide a unique contribution to the model. CONCLUSIONS: These findings suggest that the more comprehensive WMLS-R does not improve understanding of the effects of language on NP performance in an HIV+ bilingual Latino population.

Medication Adherence in HIV-Positive African Americans: The Roles of Age, Health Beliefs, and Sensation Seeking.

We examined how two critical constructs, health beliefs and sensation seeking, influence combination antiretroviral therapy adherence in HIV+ African Americans, and whether these factors mediate the association between age and adherence. Two-hundred-and-eighty-six HIV+ African Americans participated in this observational study. Path analyses revealed that higher levels of a specific health belief, perceived utility of treatment, and lower levels of a sensation-seeking component, Thrill and Adventure Seeking, directly predicted optimal adherence. The influence of age on adherence was partially mediated by lower Thrill and Adventure Seeking levels. Depression predicted adherence via perceived utility of treatment and Thrill and Adventure Seeking, whereas current substance abuse and dependence did via Thrill and Adventure Seeking. Poorer neurocognitive function had a direct, adverse effect on adherence. Our findings suggest that supporting the development of more positive perceptions about HIV treatment utility may help increase medication adherence among African Americans. This may be particularly relevant for those with higher levels of depression symptoms, which was directly associated with negative perceptions about treatment. Additionally, clinicians can assess sensation-seeking tendencies to help identify HIV+ African Americans at risk for suboptimal adherence. Compensatory strategies for medication management may help improve adherence among HIV+ individuals with poorer neurocognitive function.

Increased neurocognitive intra-individual variability is associated with declines in medication adherence in HIV-infected adults.

OBJECTIVE: There is cross-sectional evidence that neurocognitive intra-individual variability (IIV), or dispersion, is elevated in human immunodeficiency virus (HIV) disease and is associated with declines in activities of daily living, including medication adherence. METHODS: This longitudinal study extends this literature by examining whether increased neurocognitive IIV in HIV-positive persons over time predicts declines in medication adherence above and beyond changes in mean level of performance over a 6-month observation. RESULTS: After controlling for drug use, declines in mean performance, and changes in depressive symptoms, results confirmed that increases in IIV were associated with overall poorer antiretroviral medication adherence. HIV-positive individuals with the greatest increases in dispersion demonstrated marked reductions in adherence by the third month that exceeded what was observed in less variable individuals. CONCLUSIONS: Our results indicate that increases in dispersion are associated with poorer declines in medication adherence in HIV disease, which may have implications for the early detection and remediation of suboptimal antiretroviral adherence.

Socioeconomic Status and Neuropsychological Functioning: Associations in an Ethnically Diverse HIV+ Cohort.

OBJECTIVE: There is limited research examining the relationship between socioeconomic status (SES) and neuropsychological functioning, particularly in racial/ethnic minority and HIV+ populations. However, there are complex associations between poverty, education, HIV disease, race/ethnicity, and health outcomes in the US. METHOD: We explored these relationships among an ethnically diverse sample of 134 HIV+ adults using a standardized SES measure (i.e., the Hollingshead scale), a comprehensive NP test battery, and a functional evaluation (i.e., Patient's Assessment of Own Functioning Inventory and Modified Instrumental Activities of Daily Living Scale). RESULTS: Bivariate analyses showed that adult SES was significantly, positively correlated with neuropsychological performance on specific tests within the domains of verbal fluency, attention/concentration, learning, memory, processing speed, and executive functioning, and childhood SES was significantly linked to measures of verbal fluency, processing speed, and executive functioning. In a series of linear regressions, controlling for SES significantly attenuated group differences in NP test scores between racial/ethnic minority individuals and non-Hispanic White individuals. Finally, SES scores significantly differed across HIV-Associated Neurocognitive Disorder (HAND) diagnoses. In a binary logistic regression, SES was the only independent predictor of HAND diagnosis. CONCLUSIONS: HIV+ individuals with lower SES may be more vulnerable to HIV-associated neuropsychological sequelae due to prominent health disparities, although the degree to which this is influenced by factors such as test bias remains unclear. Overall, our results suggest that SES is significantly linked to neuropsychological test performance in HIV+ individuals, and is an important factor to consider in clinical practice.