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The present paper describes the methodology and sample characteristics of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project, which aimed to generate demographically-adjusted norms for a battery of neuropsychological tests in this population. The sample consisted of 254 healthy Spanish-speakers, ages 19-60 years, recruited from the U.S.-Mexico border regions of Arizona (n = 102) and California (n = 152). Participants completed a comprehensive neuropsychological test battery assessing multiple domains (verbal fluency, speed of information processing, attention/working memory, executive function, learning and memory, visual-spatial skills and fine motor skills). Fluency in both Spanish and English was assessed with performance-based measures. Other culturally-relevant data on educational, social, and language background were obtained via self-report. Demographic influences on test performances were modeled using fractional polynomial equations that allow consideration of linear and non-linear effects. There were no significant demographic differences between participants tested in Arizona and California. Age and gender were similar across education ranges. Two thirds of the sample were Spanish dominant and the remainder were considered bilingual. Individual articles in this Special Issue detail the generation of demographically adjusted T-scores for the various tests in the battery as well as an exploration of bilingualism effects. Norms developed through the NP-NUMBRS project stand to improve the diagnostic accuracy of neuropsychological assessment in Spanish-speaking young-to-middle-aged adults living in the U.S.-Mexico border region. Application of the present norms to other groups should be done with caution. [ABSTRACT FROM AUTHOR]

• People with HIV (PWH) report higher levels of depression than HIV- individuals. • Depression is higher in PWH only at low levels of CSF dopaminergic (DA) biomarkers. • Lower CSF homovanillic acid (HVA) relates to higher depression in PWH, but not HIV-. • Lower CSF HVA relates to higher CSF inflammation in PWH, but not HIV-. • PWH may show a greater response to DA agonist treatments for depression than HIV-. HIV-related neuroinflammation has been proposed as a catalyst for dopaminergic dysregulation in mesocortical pathways, which may contribute to the pathogenesis of depression. Abnormalities in dopaminergic neurotransmission and depression are common in people with HIV (PWH), however the link between dopamine (DA) and depression in PWH is poorly characterized. This study investigated CSF dopaminergic biomarkers, specifically DA and its metabolite, homovanillic acid (HVA), and examined their relationship with depressive symptoms and CSF neuroinflammatory markers in PWH and HIV-seronegative (HIV-) individuals. Participants were 102 HIV- individuals and 123 PWH (mean age = 42) who underwent neuropsychiatric evaluations and lumbar puncture. Current depression severity was classified using the Beck Depression Inventory-II (BDI-II). CSF was assayed for DA and HVA using high performance liquid chromatography and neuroinflammatory markers using immunoassays. Linear regressions modelled BDI-II scores as a function of HIV, dopaminergic biomarker z-scores, and their interaction, controlling for psychosocial factors. Correlational analyses examined dopaminergic and neuroinflammatory relationships. PWH had significantly higher BDI-II scores than HIV- participants. DA and HVA were not associated with HIV status but both significantly moderated the effect of HIV on BDI-II scores, such that PWH exhibited higher depressive symptoms than HIV- participants only at lower concentrations of HVA (z ≤ 0.06) and DA (z ≤ 0.11). In PWH only, lower HVA significantly correlated with higher BDI-II scores and higher neuroinflammation, including higher MCP-1 and IP-10. Results suggest that the pathophysiology of depression in PWH differs from that in HIV- individuals. Specifically, lower central dopaminergic activity was selectively associated with greater depressive symptoms and neuroinflammation in PWH. With the rise in consideration of DA agonists for the treatment of depression, these results suggest that PWH may show a greater response to these agents than their HIV- peers. [ABSTRACT FROM AUTHOR]

Objective: HIV disease and methamphetamine (METH) dependence share overlapping mechanisms of neurotoxicity that preferentially compromise monoamine-rich frontostriatal circuitry. However, norepinephrine (NE) function is poorly understood in HIV and METH dependence. We evaluated associations between cerebrospinal fluid (CSF) NE and HIV, METH dependence, and neurocognition. Methods: Participants included 125 adults, stratified by HIV serostatus (HIV+/HIV2) and recent METH dependence (METH+/ METH2), who underwent comprehensive neurocognitive testing and lumbar puncture. CSF NE was assayed using high-performance liquid chromatography. Multivariable regression modelled NE as a function of HIV, METH, and their interaction, adjusting for demographic and clinical factors. Pearson correlations examined relationships between NE and demographically-adjusted neurocognitive domain scores. Results: HIV significantly interacted with METH (P, 0.001) such that compared with HIV2/METH2, CSF NE was markedly elevated in the single risk-groups (HIV+/METH2: d = 0.96; HIV2/METH+: d = 0.79) and modestly elevated in the dual-risk group (HIV+/METH+: d = 0.48). This interaction remained significant after adjustment for lifetime depression, antidepressant use, and race/ethnicity. In the full sample, higher NE levels significantly correlated with worse global function (r = 20.19), learning (r = 20.23), and delayed recall (r = 20.18). Similar relationships between higher NE and worse neurocognition were detected in the METH2 groups (ie, HIV2/METH2 and HIV+/ METH2) and in the virally-suppressed persons HIV+ subgroup, but not in the METH+ groups (ie, HIV2/METH+, HIV+/METH+). Discussion: HIV and METH independently, but not additively, relate to noradrenergic excess in the central nervous system, and perturbations to noradrenergic function may represent a pathophysiological mechanism of HIV-related neurocognitive dysfunction. Consistent with prior reports that noradrenergic excess compromises hippocampal and prefrontal function, higher NE related to worse neurocognition, even among successfully treated persons with HIV. Pharmacological and psychosocial interventions that stabilize NE function may improve neurocognition in persons with HIV. [ABSTRACT FROM AUTHOR]

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes. [ABSTRACT FROM AUTHOR]

In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health–sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting. [ABSTRACT FROM AUTHOR]

With the introduction of combination antiretroviral therapy, many human immunodeficiency virus-positive (HIV+) individuals are reaching advanced age. The proportion of people living with HIV older than 50 years already exceeds 50% in many communities, and is expected to reach this level nationally by 2015. HIV and aging are independently associated with neuropathological changes, but their concurrence may have a more deleterious effect on the central nervous system (CNS). Published data about neurocognitive and neuroimaging markers of HIV and aging are reviewed. Putative factors contributing to neurocognitive impairment and neuroimaging changes in the aging HIV+ brain, such as metabolic disturbances, cardiovascular risk factors, immune senescence, and neuroinflammation, are described. The possible relationship between HIV and some markers of Alzheimer's disease is presented. Current research findings emphasize multiple mechanisms related to HIV and combination antiretroviral therapy that compromise CNS structure and function with advancing age. [ABSTRACT FROM AUTHOR]

In Nigeria, the incidence and prevalence of human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore, studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. A total of 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky performance status scale. Fifteen HIV-infected patients and 11 controls were also administered a detailed NP battery. Blood samples from eight infected subjects, three with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8 % of the HIV-1 seropositive and 16.0 % of seropositive individuals scored abnormally. Results from testing using the full NP battery showed that, overall, the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the trail making test A) to large (0.82 on action fluency), and an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Sequencing of partial pol amplicons from viral isolates revealed that two of three patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF)02_AG; all four individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of the IHDS in identifying cognitive impairment among HIV infected individuals in Nigeria. Future studies aimed at examining the burden of NCI among the population of individuals with HIV-1 infection in Nigeria and which assess the virologic correlates will contribute to the evolving understanding of the pathogenetic factors that underlie this disorder. [ABSTRACT FROM AUTHOR]

Abstract: Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH−) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n =32) and impaired (n =22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine. [Copyright &y& Elsevier]

Spanish speakers commonly use two versions of the alphabet, one that includes the sound “Ch” between C and D and another that goes directly to D, as in English. Versions of the Trail Making Test Part B (TMT-B) have been created accordingly to accommodate this preference. The pattern and total number of circles to be connected are identical between versions. However, the equivalency of these alternate forms has not been reported. We compared the performance of 35 healthy Spanish speakers who completed the “Ch” form (CH group) to that of 96 individuals who received the standard form (D group), based on whether they mentioned “Ch” in their oral recitation of the alphabet. The groups had comparable demographic characteristics and overall neuropsychological performance. There were no significant differences in TMT-B scores between the CH and D groups, and relationships with demographic variables were comparable. The findings suggest that both versions are equivalent and can be administered to Spanish speakers based on their preference without sacrificing comparability. [ABSTRACT FROM AUTHOR]

Neurocognitive disturbances associated with HIV infection may be modulated or confounded by coexisting and comorbid conditions that reflect the changing populations affected by the disease. HIV infection is often accompanied by substance dependence and/or hepatitis C co-infection. Both of these cofactors that may lead to brain dysfunction on their own, and therefore can affect the nature and course neurocognitive functioning in HIV. Improvements in antiretroviral therapies translate into greater longevity for people infected with HIV, many of whom are now entering their 6th and 7th decade of life and beyond. The increasing proportion of older persons with HIV is also the result of new infections in this age group. As aging confers additional metabolic, neurologic, and neuropsychiatric vulnerability, it is important to understand how this constellation of changes affects neurocognitive functioning in the context of HIV. [ABSTRACT FROM AUTHOR]

Research findings have suggested a need for modifications to the original nomenclature for human immunodeficiency virus (HIV)-associated neurocognitive disorders issued in 1991 by the American Academy of Neurology (AAN). The HIV Neurobehavioral Research Center (HNRC) proposed a diagnostic scheme that departs from the AAN 1991 criteria primarily in the inclusion of an asymptomatic neurocognitive impairment (ANI) category that relies on cognitive disturbances as a necessary criterion for diagnosis, without requiring declines in daily functioning, motor, or other behavioral abnormalities. In order to test the predictive validity of these two nomenclatures, the authors compared the correspondence between antemortem neurocognitive diagnoses resulting from AAN and HNRC criteria to a neuropathological diagnosis of HIV encephalitis (HIVE) made at autopsy. Agreement between the two sets of definitional criteria was 79% regarding the classification of cases as either neurocognitively normal or impaired, and 54% with regard to specific neurocognitive diagnoses. When pathological evidence of HIVE was considered as the external indicator of HIV-related brain involvement, 64% of cases were correctly classified by AAN criteria, compared to 72% by HNRC criteria. HNRC criteria had better positive predictive power (95% versus 88%), sensitivity (67% versus 56%), and specificity (92% versus 83%). Three cases with HIVE and were correctly identified by HNRC criteria for ANI but called normal by AAN criteria, supporting inclusion of an asymptomatic neurocognitive condition. The modifications to the AAN 1991 criteria proposed by the HNRC and others in the field have served as a point of departure for a recently revised consensus nomenclature. [ABSTRACT FROM AUTHOR]

While the standard 200-item version of the Paced Auditory Serial Task (PASAT) is a sensitive neuropsychological instrument, it can be quite aversive to some patients due to its length and progressively increasing difficulty. We present demographically-corrected norms for 50 and 100-item short-form versions in a sample of 560 neurologically normal adults. Age, education, and ethnicity (but not gender) were found to be significant predictors of performance. In a clinical sample of 786 HIV-infected adults, diagnostic accuracy of the 50, 100, and 200-item versions was essentially equivalent (using clinical ratings of a comprehensive neuropsychological battery as the gold standard, overall classification rates of the three PASAT versions were 71%, 74%, and 73%, respectively), with better specificity (89-92%) than sensitivity (45-53%). The 50-item version showed moderate ceiling effects, but the 100-item test did not. In a mixed clinical sample of 40 subjects, the 50-item version was administered more than twice as fast as the 200-item version, and was tolerated better (discomfort rating of 4.0 vs. 5.9 on a 10-point scale, p < .05). We conclude that in many cases the PASAT-50 and PASAT-100 provide equivalent diagnostic accuracy with a significant reduction in administration time and patient discomfort. [ABSTRACT FROM AUTHOR]

Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluated English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessmenets included the following domains: Medication Management, Cooking, Finances, Shopping and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p<.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers. [ABSTRACT FROM AUTHOR]

Background Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immunomodulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH. Methods Cross-sectional single-center (United States) analysis in 184 PWH on ART with plasma HIV RNA < 200 copies/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and clinical conditions. Results Participants were mostly middle-aged men, with median CD4+ T cells of 620/µL. In adjusted models, SSRI use was associated with 3 PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=.14, P =.040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=−.12, P =.042); and higher plasma sCD14 with lower sCD40L (aβ=.15, P =.042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=.22, P =.004). Statins and ACEIs showed no association. Conclusions SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation, and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH. [ABSTRACT FROM AUTHOR]

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50–75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = −3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = −3.39, SE = 1.31, p = 0.01) and MetS (B = −2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH. [ABSTRACT FROM AUTHOR]

• Methamphetamine (METH) alters dopamine (DA) integrity and executive function (EF). • METH-related EF deficits are greatest in Met/Met-carriers of COMT val158met gene. • METH+ have lower CSF DA levels than METH- only in Met/Met, but not Val-carriers. • CSF DA is highest in METH- Met/Met-and only correlates with better EF in this group. • Slow DA clearance conferred by Met/Met-exacerbates METH-related DA injury. The Met-allele of the COMT Val158Met polymorphism slows metabolism and increases bioavailability of dopamine (DA) in the prefrontal cortex compared to the Val-allele. Healthy Met-carriers outperform Val-carriers on executive function (EF) tests, yet this 'advantage' disappears in methamphetamine (METH) dependence. Met-carriers may be disproportionately vulnerable to METH-related perturbations of DA, yet it is unknown whether COMT modulates METH effects on CSF DA biomarkers. Participants were 75 METH+ and 47 METH- men who underwent neurocognitive testing, COMT genotyping, and lumbar puncture. CSF was assayed for DA and its metabolite, homovanillic acid (HVA). Separate linear models regressed DA, HVA, and HVA/DA ratios on COMT , METH and their interaction. Pearson correlations examined associations between DA and EF. Significant interactions indicated that METH+ had lower DA and higher HVA/DA ratios among Met/Met, but not Val/Met-or Val/Val. Met/Met-exhibited the highest DA levels among METH-, whereas DA levels were comparable between Met/Met-and Val-carriers among METH+. Higher DA correlated with better EF in METH- Met/Met, but did not predict EF in the entire sample. DA was expectedly higher in METH- Met/Met, yet a discordant genotype-phenotype profile emerged in METH+ Met/Met, consistent with the notion that slow DA clearance exacerbates METH-associated DA dysregulation. [ABSTRACT FROM AUTHOR]

Introduction: The Val allele of the Val158Met single-nucleotide polymorphism of the catechol-o-methyltransferase gene (COMT) confers greater catabolism of dopamine (DA) in the prefrontal cortex (PFC) than the Met allele. Met/Met homozygotes typically outperform Val-carriers on tests of executive function (EF), perhaps resulting from increased DA bioavailability. Methamphetamine (METH) causes large releases of DA, which is associated with neurotoxicity and executive dysfunction in chronic METH users. We hypothesized that, contrary to its effect in non-METH-using populations, slower DA clearance conferred by Met/Met will relate to worse EF in METH users.Methods: 149 non-Hispanic White men, stratified by METH dependence (METH+/-) and COMT (Val/Val, Val/Met, Met/Met), completed three tests of EF: Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test (Stroop), and Trail Making Test Part B (Trails B). Demographically-adjusted test scores were averaged to create an EF composite T-score. We examined the interaction of METH and COMT on the EF composite and individual test T-scores, controlling for premorbid functioning and alcohol use.Results: METH group differences in EF were evident only among Met/Met carriers (beta = -9.36, p < .001) but not among Val carriers: Val/Met (beta = -1.38, p = .44) and Val/Val (beta = -4.34, p = .10). These effects were most salient on the WCST.Conclusions: In the pre-frontal hyperdopaminergic state triggered by methamphetamine, greater DA inactivation conferred by the Val allele may protect against METH-related executive dysfunction, suggesting genetically-driven differences in vulnerability to METH. [ABSTRACT FROM AUTHOR]

AbstractObjective: HIV/AIDS disproportionately affects Black and Latino people in the United States, yet there is a lack of research on predictors of neurocognitive outcomes in these groups. We examined neurocognitive performance and its key predictors across White, Black, and Latino people with HIV (PWH). Method: Participants included 586 PWH of White, Black, and Latino (English- and Spanish-speaking) background. Neurocognition was assessed via demographically-adjusted Fluid Cognition Composite T-scores from the NIH-Toolbox cognition battery, and individual tests comprising this composite. Predictors examined included sociodemographic and HIV disease characteristics, and medical, psychiatric and substance comorbidities. Results: Compared to White PWH, English-speaking Latino PWH had lower T-scores on the Fluid Cognition Composite, as well as Flanker Inhibition and Picture Sequence Memory tests. While there were no other significant group differences on Fluid Cognition, both Latino PWH language groups performed worse than Black PWH on Flanker Inhibition, and Black PWH performed worse than White PWH on List Sorting. Separate multivariable linear regression models by ethnic/racial/language group showed that significant correlates of worse Fluid Cognition included depressive symptoms among White PWH; hepatitis C co-infection among Black PWH; hypertension among English-speaking Latino PWH; and higher estimated duration of HIV disease and depressive symptoms in Spanish-speaking Latino PWH. Conclusions: Findings suggest worse neurocognition among English-speaking Latino PWH compared to Whites. Predictors of neurocognitive function among PWH differ across ethnic/racial and language groups. Consideration of these HIV disease characteristics and comorbidities may be valuable in developing targeted culturally-relevant interventions aimed at ameliorating neurocognitive dysfunction among diverse PWH. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection leads to blood–brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. Methods We studied persons with HIV (PWH) and HIV-negative (HIV−) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay. Results Participants were 45 PWH and 30 HIV− individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r  = 0.47, P  < .001). PWH had higher (more abnormal) BBB index values than HIV− individuals (mean ± SD, 0.361 ± 1.20 vs −0.501 ± 1.11; P  = .0214). HIV serostatus interacted with cannabis use frequency, such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV− individuals. Worse BBB index values were associated with higher NFL in CSF (r  = 0.380, P  = .0169). Conclusions Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity. [ABSTRACT FROM AUTHOR]

We developed demographically-corrected norms for Spanish-speakers from the U.S.-Mexico border regions of California and Arizona on two tests of motor skills - the Grooved Pegboard Test (Pegboard) and Finger Tapping Test (Tapping) - as part of a larger normative effort. Participants were native Spanish-speakers from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project (Pegboard: N = 254; Tapping: N = 183; age: 19–60 years; education: 0–20 years; 59% women). We examined the association of demographics (age, education and gender) with raw scores. Raw test scores were then converted to demographically-corrected T-scores via fractional polynomial equations. We also examined rates of impairment (T-score < 40) based on the current norms and on previously published norms for English-speaking non-Hispanic Whites and Blacks. Having more years of education was associated with better raw test score performance on both tests (p <.001), and increased age was associated with worse performance on Pegboard (p <.001). Men outperformed women on Tapping, and older age was associated with lower raw scores in men only on the Tapping non-dominant hand trial (p =.02). The normed T-scores were confirmed to be normally distributed and free from demographic influences, and resulted in expected rates of impairment. Applying existing norms for English-speaking non-Hispanic Whites and Blacks to the raw scores of Spanish-speakers generally yielded lower than expected impairment rates (2–13%), with one exception: non-dominant Pegboard, for which non-Hispanic White norms overestimated impairment (23%). Present findings underscore the importance of appropriate, population-specific normative data, even for tests of motor ability. [ABSTRACT FROM AUTHOR]

Objective: Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders. Method: 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition. Results: Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory. Conclusions: Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity. [ABSTRACT FROM AUTHOR]

Objective: Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH. Methods: Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery. Results: 27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05). Conclusion: Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH. [ABSTRACT FROM AUTHOR]

Objective: Due to decades of structural and institutional racism, minoritized individuals in the US are more likely to live in low socioeconomic neighborhoods, which may underlie the observed greater risk for neurocognitive impairment as they age. However, these relationships have not been examined among people aging with HIV. To investigate neurocognitive disparities among middle- and older-aged Latino and non-Latino White people living with HIV (PWH), and whether neighborhood socioeconomic deprivation may partially mediate these relationships. Participants and Methods: Participants were 372 adults ages 40-85 living in southern California, including 186 Latinos (94 PWH, 92 without HIV) and 186 non-Latino (NL) Whites (94 PWH, 92 without HIV) age-matched to the Latino group (for the overall cohort: Age M=57.0, SD=9.1, Education: M=12.7, SD=3.9, 38% female; for the group of PWH: 66% AIDS, 88% on antiretroviral therapy [ART]; 98% undetectable plasma RNA [among those on ART]). Participants completed psychiatric and neuromedical evaluations and neuropsychological tests of verbal fluency, learning and memory in person or remotely. Neuropsychological results were converted to demographically-unadjusted global scaled scores for our primary outcome. A neighborhood socioeconomic deprivation variable (SESDep) was generated for census tracts in San Diego County using American Community Survey 2013-2017 data. Principal components analysis was used to create one measure using nine variables comprising educational (% with high school diploma), occupational (% unemployed), economic (rent to income ratio, % in poverty, (% female-headed households with dependent children, % with no car, % on public assistance), and housing (% rented housing, % crowded rooms) factors. Census tract SESDep values were averaged for a 1km radius buffer around participants' home addresses. Results: Univariable analyses (independent samples t-tests and Chi-square tests) indicated Latinos were more likely to be female and had fewer years of formal education than NL-Whites (ps<.05). Latino PWH had higher nadir CD4 than White PWH (p=.02). Separate multivariable regression models in the overall sample, controlling for demographics and HIV status, showed Latinos had significantly lower global scaled scores than Whites (b=-0.59; 95%CI-1.13, -0.06; p=.03) and lived in more deprived neighborhoods (b=0.62; 95%CI=0.36, 0.88; p<.001). More SES deprivation was significant associated with worse global neurocognition in an unadjusted linear regression (b=-0.55; 95%CI=-0.82, -0.28; p<.001), but similar analyses controlling for demographics and HIV status, showed SESDep was not significantly related to global scaled scores (b=-0.11; 95%CI= -0.36, 0.14; p=.40). Exploratory analyses examined primary language (i.e., English vs Spanish) as a marker of Hispanic heterogeneity and its association with neurocognition and SESDep. Controlling for demographics and HIV status, both English-speaking (b=0.33; 95%CI=0.01. 0.64; p=.04) and Spanish-speaking Latinos (b=0.88; 95%CI=0.58, 1.18; p<.001) lived in significantly greater SESDep neighborhoods than Whites, with SESDep greater for Spanish-speakers than English-speakers (p<.001). However, only English-speaking Latinos had significantly lower neurocognition than Whites (b=-0.91; 95%CI=0-1.57, -0.26; p<.01; Spanish-speakers: b=-0.27; 95%CI=-0.93, 0.38; p=.41). Conclusions: Among our sample of diverse older adults living with and without HIV, English-speaking Latinos showed worse neurocognition than Whites. Though SES neighborhood deprivation was worse among Latinos (particularly Spanish-speakers) it was not associated with neurocognitive scores after adjusting for demographics. Further studies investigating other neighborhood characteristics and more nuanced markers of Hispanic heterogeneity (e.g., acculturation) are warranted to understand factors underlying aging and HIV-related neurocognitive disparities among diverse older adults. [ABSTRACT FROM AUTHOR]

There is a significant overlap between HIV infection and substance-use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are the targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 h, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic rate compared to DRD1. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase in p24 levels following DA stimulation. Conversely, DA increased the expression of these genes' transcripts at the protein level, MRP8 and MRP14, respectively, which form a complex also known as calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding of the complex to the receptor for an advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface, in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanism for the delayed effect via DRD4 on the p24 increase. To cross-validate MRP8/14 as a DA signature with a biomarker value, we tested its expression in HIV+ Meth users' postmortem brain specimens and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as the basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in specimens from participants with a detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth. [ABSTRACT FROM AUTHOR]

Neurocognitive impairment (NCI) in HIV infection occurs as a frequent complication of HIV infection and, among HIV infected individuals in Nigeria, can be detected during the early stages of infection. The presence and severity of NCI can correlate with elevation of plasma levels of monocyte activation markers. In this study was examined the potential role of gender in the occurrence of NCI and associations between NCI and levels markers of HIV disease activity.One hundred thirty-three antiretroviral-naive seropositive (SP; 94 women and 59 men) and 56 seronegative (SN; 38 women and 18 men) participants received neuropsychological testing in 7 ability domains with calculation of demographically adjusted domain scores and a global deficit score (GDS). Also measured were plasma HIV RNA levels and plasma levels of the monocyte activation markers soluble CD163 and soluble CD14.SP women in the study were younger than SP men, and SP women and men were less educated than their SN counterparts. CD4+ T cell counts, which were lower SP than for SN individuals, were higher for SN woman and SP women than for their male counterparts. Within the various ability domains, SP women scored worse than SN women with respect to verbal fluency and motor function and had higher overall mean GDS scores. In addition, SP women scored worse than SP men with respect to learning and memory. Mean log HIV viral load was higher and the frequency of non-detectable virus was lower for SP women than for SP men. Among SP women there was a borderline statistically significant correlation between sCD163 levels and GDS, and sCD14 levels were higher for impaired SP women than for non-impaired SP women. Viral load was higher for impaired SP men than non-impaired men and did not differ for impaired versus non-impaired SP women.Gender can have a significant impact on the occurrence of NCI among HIV infected individuals in Nigeria. This association appears to be linked to specific immune and viral factors, which require further study. [ABSTRACT FROM AUTHOR]

Neurocognitive impairment (NCI) in HIV infection occurs as a frequent complication of HIV infection and, among HIV infected individuals in Nigeria, can be detected during the early stages of infection. The presence and severity of NCI can correlate with elevation of plasma levels of monocyte activation markers. In this study was examined the potential role of gender in the occurrence of NCI and associations between NCI and levels markers of HIV disease activity.One hundred thirty-three antiretroviral-naive seropositive (SP; 94 women and 59 men) and 56 seronegative (SN; 38 women and 18 men) participants received neuropsychological testing in 7 ability domains with calculation of demographically adjusted domain scores and a global deficit score (GDS). Also measured were plasma HIV RNA levels and plasma levels of the monocyte activation markers soluble CD163 and soluble CD14.SP women in the study were younger than SP men, and SP women and men were less educated than their SN counterparts. CD4+ T cell counts, which were lower SP than for SN individuals, were higher for SN woman and SP women than for their male counterparts. Within the various ability domains, SP women scored worse than SN women with respect to verbal fluency and motor function and had higher overall mean GDS scores. In addition, SP women scored worse than SP men with respect to learning and memory. Mean log HIV viral load was higher and the frequency of non-detectable virus was lower for SP women than for SP men. Among SP women there was a borderline statistically significant correlation between sCD163 levels and GDS, and sCD14 levels were higher for impaired SP women than for non-impaired SP women. Viral load was higher for impaired SP men than non-impaired men and did not differ for impaired versus non-impaired SP women.Gender can have a significant impact on the occurrence of NCI among HIV infected individuals in Nigeria. This association appears to be linked to specific immune and viral factors, which require further study. [ABSTRACT FROM AUTHOR]

Objective: Methamphetamine and cannabis are two widely used substances among people living with HIV (PLWH). Whereas methamphetamine use has been found to worsen HIV-associated neurocognitive impairment, the effects of combined cannabis and methamphetamine use disorder on neurocognition in PLWH are not understood. In the present study, we aimed to determine the influence of these substance use disorders on neurocognition in PLWH and to explore if methamphetamine-cannabis effects interacted with HIV status. Method and Participants: After completing a comprehensive neurobehavioral assessment, PLWH (n = 472) were stratified by lifetime methamphetamine (M−/M+) and cannabis (C−/C+) DSM-IV abuse/dependence disorder into four groups: M−C− (n = 187), M−C+ (n = 68), M+C−, (n = 82), and M+C+ (n = 135). Group differences in global and domain neurocognitive performances and impairment were examined using multiple linear and logistic regression, respectively, while holding constant other covariates that were associated with study groups and/or cognition. Data from participants without HIV (n = 423) were added, and mixed-effect models were used to examine possible interactions between HIV and substance use disorders on neurocognition. Results: Compared with M+C+, M+C− performed worse on measures of executive functions, learning, memory, and working memory and were more likely to be classified as impaired in those domains. M−C− performed better than M+C+ on measures of learning and memory but worse than M−C+ on measures of executive functions, learning, memory, and working memory. Detectable plasma HIV RNA and nadir CD4 < 200 were associated with lower overall neurocognitive performance, and these effects were greater for M+C+ compared with M−C−. Conclusions: In PLWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. There was no evidence of an HIV × M+ interaction across groups, but neurocognition was most impacted by HIV among those with polysubstance use disorder (M+C+). Better performance by C+ groups is consistent with findings from preclinical studies that cannabis use may protect against methamphetamine's deleterious effects. [ABSTRACT FROM AUTHOR]

Objectives: The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia, but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND. Methods: A total of 108 participants (including 60 HIV-infected persons) completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible 3-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated. Results: Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75%, respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared with the gold standard NP battery, were Trail Making Test A, Wechsler Adult Intelligence Scale III Digit Symbol and Hopkins Verbal Learning Test—Revised Total Recall (sensitivity 91%, specificity 96%), and Digit Symbol, Brief Visuospatial Memory Test—Revised Total Recall and Grooved Pegboard Test—dominant hand (sensitivity 94%, specificity 91%). Conclusions: Both test combinations can be administered in less than 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination. [ABSTRACT FROM AUTHOR]

Introduction: HIV is frequently associated with deficits in brain function, including memory, psychomotor speed, executive function and attention. Early life stress (ELS) has also been shown to have a direct influence on neurocognitive performance. However, little is known about the combined impact of ELS and HIV on neurocognitive function over time. The aim of the present study was to follow a cohort of affected women, allowing us to assess the effects of HIV and childhood trauma on cognition and the change in cognition over time.Method: A battery of neurocognitive tests was administered to 117 women at baseline and then a year later. The sample included a total of 67 HIV+and 50 HIV−women, 71 with ELS and 46 without ELS. Controlling for age, education and antiretroviral therapy (ART) at baseline and 12-month follow-up, raw scores were compared across groups using a repeated-measures analysis of covariance.Results: More women were on ART at follow-up compared to baseline. Results revealed a significant combined HIV and childhood trauma effect over time on the Wisconsin Card Sorting Test (p = .003) and Category Fluency Test (p = .006). A significant individual HIV effect over time was evident on the WAIS-III Digit Symbol Test (p = .03) and the Controlled Oral Word Association Test (p = .003).Conclusion: Findings suggest better performance in abstract reasoning, speed of information processing and verbal fluency over time. While all groups showed improvements that may correspond to practice effects, effects of HIV and childhood trauma remained evident at 12-month follow-up despite greater ART uptake and improved HIV disease status. This is the first study to assess the combined impact of HIV and trauma on neurocognitive function over time in an all-female cohort with more advanced disease. [ABSTRACT FROM PUBLISHER]

Objectives: We investigated the impact of culturally relevant social, educational, and language factors on cognitive test performance among Spanish speakers living near the US–Mexico border. Methods: Participants included 254 healthy native Spanish speakers from the Neuropsychological Norms for the US–Mexico Border Region in Spanish (NP-NUMBRS) project (Age: M = 37.3, SD = 10.4; Education: M = 10.7, SD = 4.3; 59% Female). A comprehensive neuropsychological battery was administered in Spanish. Individual test scaled scores and T-scores (based on region-specific norms adjusted for age, education, and sex) were averaged to create Global Mean Scaled and T-scores. Measures of culturally relevant factors included a self-reported indicator of educational quality/access (proportion of education in Spanish-speaking country, quality of school/classroom setting, stopped attending school to work), childhood socioeconomic environment (parental education, proportion of time living in Spanish-speaking country, childhood socioeconomic and health status, access to basic resources, work as a child), and Spanish/English language use and fluency. Results: Several culturally relevant variables were significantly associated with unadjusted Global Scaled Scores in univariable analyses. When using demographically adjusted T-scores, fewer culturally relevant characteristics were significant. In multivariable analyses, being bilingual (p =.04) and working as a child for one's own benefit compared to not working as a child (p =.006) were significantly associated with higher Global Mean T-score, accounting for 9% of variance. Conclusions: Demographically adjusted normative data provide a useful tool for the identification of brain dysfunction, as these account for much of the variance of sociocultural factors on cognitive test performance. Yet, certain culturally relevant variables still contributed to cognitive test performance above and beyond basic demographics, warranting further investigation. [ABSTRACT FROM AUTHOR]

Objective: Poor sleep quality is related to worse neurocognition in older adults and in people with HIV (PWH); however, many previous studies have relied only on self-report sleep questionnaires, which are inconsistently correlated with objective sleep measures. We examined relationships between objective and subjective sleep quality and neurocognition in persons with and without HIV, aged 50 and older. Method: Eighty-five adults (PWH n = 52, HIV-negative n = 32) completed comprehensive neuropsychological testing to assess global and domain-specific neurocognition. Objective sleep quality was assessed with wrist actigraphy (total sleep time, efficiency, sleep fragmentation) for five to 14 nights. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. Results: Objective and subjective sleep measures were unrelated (p's > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%, p = 0.05) and were more likely to be using prescription and/or over the counter sleep medication (p = 0.04). In the whole sample, better sleep efficiency (p < 0.01) and greater total sleep time (p = 0.05) were associated with better learning. Less sleep fragmentation was associated with better learning (p < 0.01) and recall (p = 0.04). While PWH had slightly stronger relationships between total sleep time and sleep fragmentation, it is not clear if these differences are clinically meaningful. Better subjective sleep quality was associated with better executive function (p < 0.01) and working memory (p = 0.05); this relationship was primarily driven by the HIV-negative group. Conclusions: Objective sleep quality was associated with learning and recall whereas subjective sleep quality was associated with executive function and working memory. Therefore, assessing objective and subjective sleep quality could be clinically useful, as they are both related to important domains of cognition frequently impacted in HIV-associated neurocognitive disorders as well as neurodegenerative disorders associated with aging. Future studies should evaluate if behavioral sleep interventions can improve neurocognition. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: To investigate joint contributions of cognitive and physiologic reserve to neurocognitive SuperAging in older persons with HIV (PWH). Methods: Participants included 396 older PWH (age range: 50–69 years) who completed cross-sectional neuropsychological and neuromedical evaluations. Using published criteria, participants exhibiting global neurocognition within normative expectations of healthy 25-year-olds were classified as SuperAgers (SA; n = 57). Cognitively normal (CN; n = 172) and impaired (n = 167) participants were classified with chronological age-based norms. Cognitive reserve was operationalized with an estimate of premorbid verbal intelligence, and physiologic reserve was operationalized with a cumulative index of 39 general and HIV-specific health variables. Analysis of variance with confirmatory multinomial logistic regression examined linear and quadratic effects of cognitive and physiologic reserve on SA status, adjusting for chronological age, depression, and race/ethnicity. Results: Univariably, SA exhibited significantly higher cognitive and physiologic reserve compared with CN and cognitively impaired (d s ≥ 0.38, p s < 0.05). Both reserve factors independently predicted SA status in multinomial logistic regression; higher physiologic reserve predicted linear increases in odds of SA, and higher cognitive reserve predicted a quadratic "J-shaped" change in odds of SA compared with CN (ie, odds of SA > CN only above 35th percentile of cognitive reserve). Conclusions: Each reserve factor uniquely related to SA status, which supports the construct validity of our SA criteria and suggests cognitive and physiologic reserve reflect nonoverlapping pathways of neuroprotection in HIV. Incorporation of proxy markers of reserve in clinical practice may improve characterization of age-related cognitive risk and resilience among older PWH, even among PWH without overt neurocognitive impairment. [ABSTRACT FROM AUTHOR]

Benzodiazepine use is linked to neurocognitive impairment (NCI) in the general population and people with HIV (PWH); however, this relationship may depend on age-related factors such as medical comorbidities, which occur at an elevated rate and manifest earlier in PWH. We retrospectively examined whether chronological age or medical burden, a clinical marker for aging, moderated the relationship between benzodiazepine use and NCI in PWH. Participants were 435 PWH on antiretroviral therapy who underwent neurocognitive and medical evaluations, including self-reported current benzodiazepine use. A medical burden index score (proportion of accumulated multisystem deficits) was calculated from 28 medical deficits. Demographically corrected cognitive deficit scores from 15 neuropsychological tests were used to calculate global and domain-specific NCI based on established cut-offs. Logistic regressions separately modeled global and domain-specific NCI as a function of benzodiazepine x age and benzodiazepine x medical burden interactions, adjusting for current affective symptoms and HIV disease characteristics. A statistically significant benzodiazepine x medical burden interaction (p =.006) revealed that current benzodiazepine use increased odds of global NCI only among those who had a high medical burden (index score > 0.3 as indicated by the Johnson–Neyman analysis), which was driven by the domains of processing speed, motor, and verbal fluency. No age x benzodiazepine interactive effects on NCI were present. Findings suggest that the relationship between BZD use and NCI among PWH is specific to those with greater medical burden, which may be a greater risk factor for BZD-related NCI than chronological age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon [gamma]-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S). Methods: A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and [beta]2 microglobulin ([beta]2m) in the CSF and serum were quantified using different immunoassays. Results: Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum [beta]2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and [beta]2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum [beta]2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024). Discussion: We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B. [ABSTRACT FROM AUTHOR]

Background: To examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline. Methods: Four hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6-12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics. Results: In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline. Conclusions: Latino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities. [ABSTRACT FROM AUTHOR]

Detailed neuropsychological testing was performed on 133 human immunodeficiency virus (HIV) seropositive (SP) and 77 HIV seronegative (SN) individuals, 86 % with early stage HIV infection in Nigeria, to determine the frequency of HIV-related neurocognitive impairment among the HIV-infected group. The tests were administered to assess the following seven ability domains: speed of information processing, attention/working memory, executive functioning, learning, memory, verbal fluency, and motor function motor. Demographically corrected individual test scores and scores for each domain or reflecting a global deficit (a global deficit score, or GDS) were compared for the SP and SN groups. SP participants were older, had fewer years of education, were more likely to be married, differed in ethnicity, and had higher depression scores than SN individuals. Within the seven ability domains, SP performed worse than SN with respect to speed of information processing, executive function, learning, memory, and verbal fluency and also on the global measure. SP were also more frequently impaired on tests of SIP, and there was a borderline increase in the frequency of global impairment. On the individual tests, SP performed worse than SN on four tests that assessed learning, verbal fluency, memory, and motor function (the Timed Gait). SP subjects, however, performed better than SN on the Finger-tapping test, also a motor task. Performance by SP subjects was not associated on the timed gait which showed a borderline statistically significant correlation with CD4 counts. However, there were significant correlations between viral load measurements and individual tests of speed of information processing, executive function, learning, and verbal fluency and with overall executive function and a borderline correlation with the GDS. Depression scores for SP were associated with impairment on only a single test of executive function. These results demonstrate the ability of these assessments to identify areas of impairment that may be specifically linked to a history of HIV infection among individuals in Nigeria. Confirmation of these findings awaits analyses using data from a larger number of control subjects. [ABSTRACT FROM AUTHOR]

Objective: Rates of HIV are disproportionately high among Black individuals in the United States (CDC, 2020). Black individuals are at increased risk for neurocognitive impairment due to HIV (Marquine et al., 2016) and experience health disparities including increased morbidity and mortality (Asari, 2018; Manly et al., 1998). We sought to examine the relationship between perceived quality of healthcare and neuropsychological functioning among people living with HIV (PLWH) who identify as Black compared to those who are non-Black. Participants and Methods: 151 PLWH in the Los Angeles area (52% Black, age = 49.85 ± 10.54, education = 13.23 ± 2.11; 87% cisgender men, 8% cisgender women, 1% transgender men, 3% transgender women) completed comprehensive neuropsychological (NP) assessments (from which demographically-corrected domain and global T-scores were derived), psychiatric and sociodemographic interviews, and self-report questionnaires, including a measure of perceived healthcare quality (i.e., QUOTE-HIV). Statistical analyses included chi-square, t-test, ANOVA, and stepwise linear regression. Results: Only 14% of Black PLWH had private healthcare insurance (versus Medicare/Medicaid) compared to 33% of nonBlack PLWH (x2=11.33, p<.01). Black participants were significantly older than nonBlack participants (p<.01), but did not differ on gender, education, income, CD4 count, or HIV viral load. Younger Black participants (based on a median split for age; n = 23) reported the lowest perceived quality of healthcare (i.e., QUOTE-HIV total performance score), while older Black participants (n = 56) reported the highest perceived care (F = 3.80, p =.01), but the same relationship was not observed in nonBlack participants. In a stepwise multivariate regression model, including demographic and virological factors as well as healthcare quality, only household income and overall perceived healthcare quality (i.e., QUOTE-HIV total performance score) were significantly associated with Global NP T-scores among Black PLWH (R2=.12, F(1, 66)=4.46, p=.02). Conclusions: When assessing healthcare quality and healthcare experiences among people living with HIV, race and age are important to consider. Private healthcare coverage may be less accessible to people of color, and in a multivariate model, only income and healthcare quality significantly predicted neuropsychological functioning in Black PLWH. When examining HIV and health outcomes, the complex relationships among quality of healthcare and health disparities, neuropsychological functioning, and structural racism warrant further investigation. [ABSTRACT FROM AUTHOR]

HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV −) and lifetime MDD (MDD + /MDD −), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV − /MDD − , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD +. Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: Research into the biological processes that increase susceptibility to methamphetamine dependence has been conducted primarily in Asian populations. Using a case–control design this study''s purpose was to explore, among a population of methamphetamine-dependent Caucasians, six putative single nucleotide polymorphisms previously found to be associated with methamphetamine dependence in Asian populations. A total of 193 non-psychotic males (117 methamphetamine-dependent and 76 controls) were genotyped for variants located in six genes (AKT1, ARRB2, BDNF, COMT, GSTP1, OPRM1). Genotypic and allelic frequencies, odds ratios, and 95% confidence intervals were calculated. None of the putative gene associations was significantly replicated in our sample of Caucasian men. Effect size comparisons suggest a trend toward allelic divergence for arrestin beta 2 (ARRB2) and glutathione S-transferase P1 (GSTP1) and allelic convergence for brain-derived neurotrophic factor (BDNF). Results provide preliminary support for further exploration and validation of candidate single nucleotide polymorphisms (SNPs) for methamphetamine (METH) dependence reported among Asian populations across other ethnic/ancestral groups. [Copyright &y& Elsevier]

Abstract: Background: When antiretroviral therapy does not fully suppress HIV replication, suboptimal levels of antiretrovirals can select for antiretroviral resistant variants of HIV. These variants may exhibit reduced replication capacity and result in lower viral loads in blood. Our study evaluated whether antiretroviral resistance was associated with viral loads in the cerebrospinal fluid (CSF) and better neuropsychological (NP) performance. Methods: We enrolled 94 participants and each participant underwent a comprehensive neuromedical evaluation that used structured clinical assessments of medical history, ART and other medication use, comprehensive NP testing, and neurological and general physical signs of disease. Blood was collected by venipuncture, and all participants were offered lumbar puncture. Univariate and multivariate statistical methods were used to analyze the relationship between antiretroviral resistance, blood and CSF HIV RNA levels, substance use, and NP performance. Results: Antiretroviral resistance, detected in blood, was associated with lower CSF viral loads (p <0.01) and better NP performance (p =0.04) in multivariate analyses, independent of past and current ARV use and blood viral loads (model: p <0.01). However, HIV RNA levels in CSF did not independently correlate with NP performance. Low viral loads in the CSF limited our ability to investigate the relationship between antiretroviral resistance detected in CSF and NP performance. Conclusions: Even in the absence of ART, antiretroviral resistance-associated mutations correlate with better NP performance possibly because these mutations reflect reduced neurovirulence compared with wild-type HIV. [Copyright &y& Elsevier]

The article presents a study which highlights the importance of evaluating beliefs on HIV infection, prevention and risk perception in the Ethiopian immigrant population in San Diego, California. The study was conducted among Ethiopians over the age of 18. The results show that even well educated individuals hold basic misconceptions about HIV transmission therefore, there is a need for focused HIV education programs in the community. It states that although most participants viewed HIV as a fatal disease, nearly one third of them assumed that HIV was curable. In addition, the results have provided information on specific areas justifying further investigation.

Background: Cognitive complications persist in persons with HIV during suppressive antiretroviral therapy (ART). Low levels of HIV during ART could contribute to these complications. In this study, we measured cerebrospinal fluid (CSF) HIV using a single-copy assay (SCA) to investigate a possible relationship between low-level HIV and cognition. Design/Methods: SCA data were analyzed from 3 consecutively paired CSF-plasma specimens collected over a mean of 456 days from 96 participants on suppressive ART. Using mixed models, the presence of CSF HIV by SCA as a risk factor for worse neurocognitive performance was examined. Results: At baseline on the SCA, 45.8% of participants had detectable plasma HIV RNA (median 8 copies/mL and interquartile range = 3-17 among detectable values) and 17.7% had detectable CSF HIV RNA (median CSF concentration= 3 copies/mL and interquartile range= 2-13 among detectable values). The frequency of CSF HIV RNA detection declined over time in CSF (P = 0.018) with a trend toward decline in plasma (P = 0.064). Detectable CSF HIV RNA during the study was associated with worse performance in the domains of recall (P = 0.014) and motor (P = 0.040) and a trend with worse overall global performance (P = 0.078). Integrase inhibitor use, although very infrequent in this cohort, was associated with better performance in 2 domains. Conclusions: Low-level CSF HIV RNA declines with time but is associated with worse cognitive performance in 2 domains. Addi Additional research is needed to better understand the relationship between HIV RNA persistence during long-term ART and central nervous system complications in persons with HIV. [ABSTRACT FROM AUTHOR]

Studies whether methamphetamine (METH) increases HIV replication in humans. Evaluation of HIV loads in HIV-positive METH users and non-users; Background on the groups studied; Plasma virus loads; Cerebrospinal fluid virus loads; Stratification by use of highly active antiretroviral therapy; Results suggesting that abstinence programs are a key component of effective treatment of HIV in METH-abusing population.

The directions specified in our first contrast codes appear to have caused parameter estimation issues, though both sets of contrasts below produce the same model-fitted values, and other model estimates appear to remain unchanged. After re-examining the analysis syntax and implementing another contrast coding strategy with the same comparisons (backward deviance coding), but which are specified in different directions (see below), estimates matched the fitted values displayed in the profile plots. Models examining interactions between the substance use group and HIV status/characteristics were not impacted by the contrast codes operationalization error, as contrasts were comparison coded vs. [Extracted from the article]

Background: Even in the era of suppressive antiretroviral therapy, people with HIV (PWH) suffer greater exposure to inflammation than their uninfected peers. Although poor social support and social isolation have been linked to systemic inflammation in the general population, it is not known whether this is true also among PWH. Methods: People with and without HIV infection were enrolled in a community-based, single-center study. Primary predictors were the Medical Outcomes Study Social Support Survey, and outcomes were a panel of inflammatory biomarkers (ICAM-1, MCP-1, IL-6, IL-8, IP-10, C-reactive protein, D-dimer, VEGF, sCD14, and uPAR) in blood plasma and cerebrospinal fluid (CSF). Results: PWH had worse positive social support (P = 0.0138) and affectionate support (P = 0.0078) than did HIV- individuals. A factor analysis was used to group the biomarkers into related categories separately for each fluid. Levels of 3 of the 4 plasma factors were significantly higher in PWH than HIV- (ps = 0.007, 0.001, and 0.0005, respectively). Levels of 1 of the 3 CSF factors also were significantly higher in PWH than HIV- (P = 0.0194). In the combined PWH and HIV- cohort, poorer social support was associated with higher levels of a factor in plasma loading on MCP-1, IL-8, and VEGF (P = 0.020) and with a CSF factor loading on MCP-1 and IL-6 (P = 0.006). Conclusion: These results suggest that enhancing social support might be an intervention to reduce inflammation and its associated adverse outcomes among PWH. [ABSTRACT FROM AUTHOR]

The Wisconsin Card Sorting Test (WCST) is among the most commonly used tests of executive functioning. We aimed to generate normative data on the 64-item version of this test (WCST-64) for Spanish-speakers living in the U.S.–Mexico Border region. Participants included 189 native Spanish-speakers (Age: 19–60; Education: 0–20; 59.3% female) from the Neuropsychological Norms for the U.S.–Mexico Border Region in Spanish (NP-NUMBRS) project who completed the WCST-64. Univariable and interactive associations between demographic variables and raw scores were examined via Spearman correlations, Wilcoxon Rank-sum tests and linear regressions. T-scores for various WCST-64 measures (Total Errors, Perseverative Responses, Perseverative Errors, Conceptual Level Responses and Number of Categories) were obtained using fractional polynomial equations with weights for age, education, and gender. Percentile scores were reported for Failures to Maintain Set. Rates of impairment (T-score < 40) were calculated by applying the newly developed norms and published norms for non-Hispanic English-speaking Whites and Blacks. Older age was associated with worse performance and education was linked to better performance on most WCST-64 raw scores, with stronger education effects among females than males. The norms developed here resulted in expected rates of impairment (14–16% across measures). Applying published norms for non-Hispanic Blacks resulted in generally comparable impairment rates. In contrast, applying previously published norms for non-Hispanic Whites overestimated impairment (38–52% across measures). These data will enhance interpretation performance on the WCST-64 for Spanish-speakers living in the U.S.–Mexico Border region. Future work will need to examine the generalizability of these norms to other Hispanic/Latino groups. [ABSTRACT FROM AUTHOR]