Cognitive Impairment in Tuberculous Meningitis.

BACKGROUND: Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described. METHODS: A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. RESULTS: Of 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19). CONCLUSIONS: Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.

Cognitive Performance, as well as Depression, Alcohol Use, and Gender, predict Anti-Retroviral Therapy Adherence in a South African Cohort of People with HIV and Comorbid Major Depressive Disorder.

Depression and cognitive impairment, which commonly coexist in people with HIV (PWH), have been identified as potential barriers to optimal antiretroviral therapy (ART) adherence. We investigated associations between cognitive performance, depression (as well as other sociodemographic, psychosocial and psychiatric variables) and ART adherence in a South African cohort of PWH with comorbid major depressive disorder (MDD). Cognitive performance and ART adherence were assessed at two time points 8 months apart (Nbaseline = 105, Nfollow-up = 81). Adherence was indicated by self-report, objective measures (Wisepill usage and plasma tenofovir-diphosphate levels), and HIV viral suppression. Mixed-effects regression models examined associations across both time points. Univariate models detected no significant associations between cognitive performance (globally and within-domain) and ART adherence. Multivariate modelling showed increased depression severity (ß = - 0.54, p < 0.001) and problematic alcohol use (ß = 0.73, p = 0.015) were associated with worse adherence as measured subjectively. Being female (OR 0.27, p = 0.048) and having better global cognitive performance (OR 1.83, p = 0.043) were associated with better adherence as indicated by viral suppression. This study identifies poor global cognitive performance, as well as depression and problematic alcohol use, as potential barriers to optimal ART adherence in PWH and comorbid MDD. Hence, clinicians could consider assessing for cognitive deficits, depression, and problematic alcohol use, and should endeavour to provide the appropriate support so as to improve adherence.

Mental and cognitive healthcare training targeting primary healthcare workers providing HIV services in Africa: a scoping review.

Mental health and neurocognitive functioning remain a concern among people living with HIV. Symptomatic neurocognitive impairment (NCI) and mental illness can cause difficulties in daily functioning, including problems adhering to treatment. However, many healthcare workers in resource-limited settings have limited knowledge about the relationship between HIV and NCI. A synthesis of available literature on mental health and NCI training provided to healthcare workers delivering HIV services in Africa, is lacking. We conducted a scoping review of published literature to identify training interventions which targeted healthcare workers providing careto people with HIV in Africa. Ten studies met the inclusion criteria. One study focused on NCI, two studies mentioned HIV-associated dementia and seven studies were centred on common mental health disorders. Most studies used a multi-method training approach, with pre-and post-testing as the main evaluation technique. This review highlights the gap in training interventions addressing NCI in Africa. Although there is some commitment to building capacity for mental health and NCI assessment among healthcare workers in this setting, this review suggests that there is a need for research to develop and evaluate training interventions for healthcare workers delivering HIV services in Africa.

Cognitive performance in a South African cohort of people with HIV and comorbid major depressive disorder.

Cognitive performance in people with HIV (PWH) may be affected by brain injury attributable to the infection itself, by other medical and psychiatric comorbidities (including major depressive disorder; MDD), and by psychosocial factors (e.g., education, food insecurity). We investigated effects of these variables on cognitive performance in a South African cohort of PWH with comorbid MDD and incomplete adherence to antiretroviral therapy (ART). We also examined (a) associations of depression severity with cognitive performance, and (b) whether improvement in depression led to improved cognitive performance. Participants (N = 105) completed baseline neuropsychological, psychiatric, and sociodemographic assessments. Subsequently, 33 were assigned to a cognitive-behavioural therapy for ART adherence and depression (CBT-AD) and 72 to standard-of-care treatment. Eight months post-baseline, 81 (nCBT-AD = 29) repeated the assessments. We investigated (a) baseline associations between sociodemographic, medical, and psychiatric variables and cognitive performance, (b) whether, from baseline to follow-up, depression and cognitive performance improved significantly more in CBT-AD participants, and (c) associations between post-intervention improvements in depression and cognitive performance. At baseline, less education (ß = 0.62) and greater food insecurity (ß = -0.20) predicted poorer overall cognitive performance; more severe depression predicted impairment in the attention/working memory domain only (ß = -0.25). From baseline to follow-up, depression decreased significantly more in CBT-AD participants (p = .017). Improvement over time in depression and cognitive performance was not significantly associated except in the attention/working memory domain (p = .026). Overall, factors associated with cognitive performance were unrelated to brain injury. We conclude that clinicians examining PWH presenting with cognitive difficulties must assess depression, and that researchers investigating cognitive impairment in PWH must collect information on psychosocial factors.

Moving on From HAND: Why We Need New Criteria for Cognitive Impairment in Persons Living With Human Immunodeficiency Virus and a Proposed Way Forward.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) criteria are frequently used to describe cognitive impairment in persons living with HIV (PLWH) across diverse populations globally. These criteria typically find 20-60% of PLWH meet criteria for HAND, which does not tally with clinical observations in the modern era that cognitive disorders present relatively infrequently. Most with HAND have asymptomatic neurocognitive impairment; however, the significance of low cognitive test performance without symptoms is uncertain. Methods underlying HAND criteria carry a false-positive rate that can exceed 20%. Comorbidities, education, and complex socioeconomic factors can influence cognitive test performance, further increasing the potential for misclassification. We propose a new framework to characterize cognitive impairment in PLWH that requires a clinical history and acknowledges the multifactorial nature of low cognitive test performance. This framework is intended to be applicable across diverse populations globally, be more aligned with clinical observations, and more closely represent HIV brain pathology.

Rates of cognitive impairment in a South African cohort of people with HIV: variation by definitional criteria and lack of association with neuroimaging biomarkers.

There is wide variation in the reported prevalence of cognitive impairment in people with HIV (PWH). Part of this variation may be attributable to different studies using different methods of combining neuropsychological test scores to classify participants as either cognitively impaired or unimpaired. Our aim was to determine, in a South African cohort of PWH (N = 148), (a) how much variation in reported rates was due to method used to define cognitive impairment and (b) which method correlated best with MRI biomarkers of HIV-related brain pathology. Participants completed detailed neuropsychological assessment and underwent 3 T structural MRI and diffusion tensor imaging (DTI). We used the neuropsychological data to investigate 20 different methods of determining HIV-associated cognitive impairment. We used the neuroimaging data to obtain volumes for cortical and subcortical grey matter and total white matter and DTI metrics for several white matter tracts. Applying each of the 20 methods to the cognitive dataset resulted in a wide variation (20-97%) in estimated rates of impairment. Logistic regression models showed no method was associated with HIV-related neuroimaging abnormalities as measured by structural volumes or DTI metrics. We conclude that for the population from which this sample was drawn, much of the variation in reported rates of cognitive impairment in PWH is due to the method of classification used, and that none of these methods accurately reflects biological effects of HIV in the brain. We suggest that defining HIV-associated cognitive impairment using neuropsychological test performance only is insufficient; pre-morbid functioning, co-morbidities, cognitive symptoms, and functional impairment should always be considered.

Sex Differences in the Cognitive Performance of a South African Cohort of People With HIV and Comorbid Major Depressive Disorder.

Women with HIV (WWH) may be more vulnerable to cognitive impairment than men with HIV (MWH), which may be explained by the direct effects of HIV or by sociodemographic and psychiatric characteristics. We recruited 105 people with HIV (PWH; 76 women) with incomplete antiretroviral therapy adherence, comorbid major depressive disorder, and socioeconomically disadvantaged backgrounds. Participants completed neuropsychological testing and measures gathering sociodemographic, medical, and psychiatric information. We compared WWH and MWH cognitive performance using unadjusted and adjusted regressions, and within each respective group, we explored predictors of cognitive performance. Results showed no significant between-sex differences in cognitive performance, both globally and within domains. Fewer years of education (ß = 0.94), illiteracy (ß = 4.55), and greater food insecurity (ß = -0.28) predicted lower cognitive performance in WWH but not MWH. We conclude that sex differences in PWH are likely due to sample characteristics representing broader inequalities, rather than true biological differences.

Cognitive impairment in people living with HIV: consensus recommendations for a new approach.

Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. The 2007 criteria for HIV-associated neurocognitive disorders (HAND), sometimes called the Frascati criteria, can falsely classify over 20% of cognitively healthy individuals as having cognitive impairment. Minimum criteria for HAND are met on the basis of performance on cognitive tests alone, which might not be appropriate for populations with diverse educational and socioeconomic backgrounds. Imprecise phenotyping of cognitive impairment can limit mechanistic research, biomarker discovery and treatment trials. Importantly, overestimation of cognitive impairment carries the risk of creating fear among people living with HIV and worsening stigma and discrimination towards these individuals. To address this issue, we established the International HIV-Cognition Working Group, which is globally representative and involves the community of people living with HIV. We reached consensus on six recommendations towards a new approach for diagnosis and classification of cognitive impairment in people living with HIV, intended to focus discussion and debate going forward. We propose the conceptual separation of HIV-associated brain injury - including active or pretreatment legacy damage - from other causes of brain injury occurring in people living with HIV. We suggest moving away from a quantitative neuropsychological approach towards an emphasis on clinical context. Our recommendations are intended to better represent the changing profile of cognitive impairment in people living with HIV in diverse global settings and to provide a clearer framework of classification for clinical management and research studies.

Risky Decision Making Under Stressful Conditions: Men and Women With Smaller Cortisol Elevations Make Riskier Social and Economic Decisions.

Men often make riskier decisions than women across a wide range of real-life behaviors. Whether this sex difference is accentuated, diminished, or stable under stressful conditions is, however, contested in the scientific literature. A critical blind spot lies amid this contestation: Most studies use standardized, laboratory-based, cognitive measures of decision making rather than complex real-life social simulation tasks to assess risk-related behavior. To address this blind spot, we investigated the effects of acute psychosocial stress on risk decision making in men and women (N = 80) using a standardized cognitive measure (the Iowa Gambling Task; IGT) and a novel task that simulated a real-life social situation (an online chatroom in which participants interacted with other men and women in sexually suggestive scenarios). Participants were exposed to either an acute psychosocial stressor or an equivalent control condition. Stressor-exposed participants were further characterized as high- or low-cortisol responders. Results confirmed that the experimental manipulation was effective. On the IGT, participants characterized as low-cortisol responders (as well as those in the Non-Stress group) made significantly riskier decisions than those characterized as high-cortisol responders. Similarly, in the online chatroom, participants characterized as low-cortisol responders (but not those characterized as high-cortisol responders) were, relative to those in the Non-Stress group, significantly more likely to make risky decisions. Together, these results suggest that at lower levels of cortisol both men and women tend to make riskier decisions in both economic and social spheres.

Cognitive Differences between Men and Women with HIV: A Systematic Review and Meta-Analysis.

OBJECTIVE: Although many studies report that women with HIV (WWH) are more vulnerable to cognitive impairment than men with HIV (MWH), this trend is not described consistently in the literature. In this systematic review and meta-analysis, we investigated whether the weight of evidence supports the existence of a significant sex difference in cognitive functioning among people with HIV and, if so, whether specific domains are affected. METHOD: A systematic literature search retrieved 4,062 unique articles published between January 2000 and June 2019. Eligibility criteria were that studies directly compared adult WWH and MWH using a neuropsychological test battery. After extensive screening, we included 11 studies in the systematic review (N = 3,333) and 6 in the meta-analysis (N = 2,852). RESULTS: Six studies included in the systematic review found WWH performed significantly more poorly on measures of cognitive performance than MWH; the other five found no sex differences. Meta-analytic results indicated that WWH performed significantly more poorly than MWH in three cognitive domains (psychomotor coordination, visuospatial learning, and memory), but magnitudes of effect sizes were small (d = -.16, -.43, and - .30, respectively). Analyses detected no sex differences in global cognitive functioning and in the other cognitive domains. CONCLUSIONS: Sex differences in cognitive performance are small, and sociodemographic and psychiatric characteristics of WWH and MWH differ between studies. Cognitive differences between WWH and MWH may be explained by sex-based variation in these characteristics, the impact of which seems to outweigh that of HIV-related clinical variables (e.g., CD4 count and viral load).

Prevalence of HIV-1 Infection in an elderly rural population and associations with neurocognitive impairment.

OBJECTIVE: We explored the prevalence of HIV infection in older rural South Africans and its associations, as well as the point prevalence of dementia and its associations with HIV and aging. DESIGN: We utilized a cross-sectional analytic design. METHODS: Using the brief Community Screening Instrument for Dementia together with a rapid HIV test, we conducted a home-based screening survey among 1150 older South Africans. We explored the prevalence of HIV and dementia, and their associations using descriptive statistics and logistic regression analysis. RESULTS: The HIV prevalence was 4.78%. Overall, participants were on average 71.3 years old, with nearly 70% having no primary school education. HIV+ participants were significantly younger, more likely to be single and had lower BMI. The overall dementia prevalence was 11.04%. HIV+ participants had higher rates of dementia compared with HIV- participants (18.18 vs. 10.68%) but the difference was NS. In adjusted analysis, screened dementia was associated with older age, the presence of self-reported depression and HIV+ status. Participants were also more likely to self-report cognitive impairment if they were older, depressed and had objective evidence of dementia. CONCLUSION: Infection with HIV in rural older South Africans is a prevalent problem, and together with older age, is a significant contributor to cognitive impairment. It is possible that HIV infection contributes to dementia on the basis of an acceleration of degeneration - because our HIV-infected participants were younger - AND an accentuation of aging - because of the higher rates of impairment for similar age groups.