Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive f... more Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive functioning are vital tools in the early detection of HIV-associated NC impairment. The HIV Neurobehavioral Research Center’s International Neurobehavioral Battery (HNRC Battery) is one such diagnostic tool and has shown cultural validity in several international neuroHIV studies. However, no published norms are currently available for the full HNRC Battery in South Africa. To accurately interpret NC test results, appropriate reference norms are required. In light of this challenge, data were collected from 500 healthy, HIV-uninfected participants to develop demographically corrected South African norms. When demographically corrected United States of America (U.S.) norms were applied to the performance scores of our neurologically intact, HIV-negative sample, an impairment rate of 62.2% was observed compared to a 15.0% impairment rate when the newly generated South African norms were app...
Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a sign... more Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma...
HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-tak... more 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 relat...
The National Children's Study Cognitive Health Domain Team developed detailed plans for asses... more The National Children's Study Cognitive Health Domain Team developed detailed plans for assessing cognition longitudinally from infancy to early adulthood. These plans identify high-priority aspects of cognition that can be measured efficiently and effectively, and we believe they can serve as a model for future large-scale longitudinal research. For infancy and toddlerhood, we proposed several paradigms that collectively allowed us to assess six broad cognitive constructs: (1) executive function skills, (2) episodic memory, (3) language, (4) processing speed, (5) spatial and numerical processing, and (6) social cognition. In some cases, different trial sequences within a paradigm allow for the simultaneous assessment of multiple cognitive skills (e.g., executive function skills and processing speed). We define each construct, summarize its significance for understanding developmental outcomes, discuss the feasibility of its assessment throughout development, and present our pla...
Annals of Clinical and Translational Neurology, 2020
ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns... more ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact.MethodsAmbulatory, community‐dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co‐morbidities. Adjusted odds ratios were calculated for follow‐up neuropathy outcomes.ResultsOf 254 participants, 21.3% were women, 57.5% were non‐white. Mean baseline age was 43.5 years. Polyneuropathy prevalence increased from 25.7% to 43.7%. Of 173 participants initially pain‐free, 42 (24.3%) had incident neuropathic pa...
Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and ... more Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n = 20), HIV mono-infected (n = 48), HIV/HCV co-infected (n = 12), and HIV-/HCV-uninfected controls (n = 48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three...
The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency&q... more The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency", computerized assessment developed to measure the full spectrum of emotional health. Though comprehensive, the NIHTB-EB's 17 scales may be unwieldy for users aiming to capture more global indices of emotional functioning. NIHTB-EB was administered to 1,036 English-speaking and 408 Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and developed factor analysis-based summary scores. Census-weighted norms were presented for English speakers, and sample-weighted norms were presented for Spanish speakers. Exploratory factor analysis for both English- and Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory factor analysis supported similar factor structures for English- and Sp...
This study examined the influence of Hispanic ethnicity and language/cultural background on perfo... more This study examined the influence of Hispanic ethnicity and language/cultural background on performance on the NIH Toolbox Cognition Battery (NIHTB-CB). Participants included healthy, primarily English-speaking Hispanic (n = 93; Hispanic-English), primarily Spanish-speaking Hispanic (n = 93; Hispanic-Spanish), and English speaking Non-Hispanic white (n = 93; NH white) adults matched on age, sex, and education levels. All participants were in the NIH Toolbox national norming project and completed the Fluid and Crystallized components of the NIHTB-CB. T-scores (demographically-unadjusted) were developed based on the current sample and were used in analyses. Spanish-speaking Hispanics performed worse than English-speaking Hispanics and NH whites on demographically unadjusted NIHTB-CB Fluid Composite scores (ps < .01). Results on individual measures comprising the Fluid Composite showed significant group differences on tests of executive inhibitory control (p = .001), processing spee...
Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected pe... more Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be...
There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (H... more There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART). But the prevalence of milder forms of HAND still remains high. Data from systematically conducted studies on the effects of ART on cognition are scanty in India, where HIV-1 clade C is prevalent. The purpose of the present study was to assess the effect of antiretroviral therapy in HIV-seropositive (HIV+) individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and domain-specific levels of cognitive functioning were determined using a locally recruited normative sample, and a change in neurocognitive functioning at the 1-year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6 % of the HIV+ group at baseline. At the 1-year follow-up, the group showed significant improvement in the Learning domain (p < 0.05). HIV+ individuals showing improvement in the global cognitive scores had a signific...
Journal of acquired immune deficiency syndromes (1999), Jan 2, 2014
We tested our hypothesis that abdominal obesity when associated with increased levels of systemic... more We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Cross-sectional SETTING:: Six Academic Centers PARTICIPANTS:: 152 patients with plasma HIV RNA <1,000copies/ml had clinical evaluations and cognitive function quantified by global deficit scores (GDS). GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year of the index visit, GDS remained worse in patients with IL-6 levels in the high-versus-low tertile (p=0.02). Path an...
Journal of clinical and experimental neuropsychology, 2014
In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate ... more In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals' premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found that this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population. The Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants; a subset of 48 HIV+ individuals completed a second study visit (M = 14.4 months), in which the alternate version of the WRAT-4 was administered. Although HIV+ individuals evidenced worse current neur...
Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive f... more Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive functioning are vital tools in the early detection of HIV-associated NC impairment. The HIV Neurobehavioral Research Center’s International Neurobehavioral Battery (HNRC Battery) is one such diagnostic tool and has shown cultural validity in several international neuroHIV studies. However, no published norms are currently available for the full HNRC Battery in South Africa. To accurately interpret NC test results, appropriate reference norms are required. In light of this challenge, data were collected from 500 healthy, HIV-uninfected participants to develop demographically corrected South African norms. When demographically corrected United States of America (U.S.) norms were applied to the performance scores of our neurologically intact, HIV-negative sample, an impairment rate of 62.2% was observed compared to a 15.0% impairment rate when the newly generated South African norms were app...
Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a sign... more Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma...
HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-tak... more 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 relat...
The National Children's Study Cognitive Health Domain Team developed detailed plans for asses... more The National Children's Study Cognitive Health Domain Team developed detailed plans for assessing cognition longitudinally from infancy to early adulthood. These plans identify high-priority aspects of cognition that can be measured efficiently and effectively, and we believe they can serve as a model for future large-scale longitudinal research. For infancy and toddlerhood, we proposed several paradigms that collectively allowed us to assess six broad cognitive constructs: (1) executive function skills, (2) episodic memory, (3) language, (4) processing speed, (5) spatial and numerical processing, and (6) social cognition. In some cases, different trial sequences within a paradigm allow for the simultaneous assessment of multiple cognitive skills (e.g., executive function skills and processing speed). We define each construct, summarize its significance for understanding developmental outcomes, discuss the feasibility of its assessment throughout development, and present our pla...
Annals of Clinical and Translational Neurology, 2020
ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns... more ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact.MethodsAmbulatory, community‐dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co‐morbidities. Adjusted odds ratios were calculated for follow‐up neuropathy outcomes.ResultsOf 254 participants, 21.3% were women, 57.5% were non‐white. Mean baseline age was 43.5 years. Polyneuropathy prevalence increased from 25.7% to 43.7%. Of 173 participants initially pain‐free, 42 (24.3%) had incident neuropathic pa...
Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and ... more Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n = 20), HIV mono-infected (n = 48), HIV/HCV co-infected (n = 12), and HIV-/HCV-uninfected controls (n = 48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three...
The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency&q... more The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency", computerized assessment developed to measure the full spectrum of emotional health. Though comprehensive, the NIHTB-EB's 17 scales may be unwieldy for users aiming to capture more global indices of emotional functioning. NIHTB-EB was administered to 1,036 English-speaking and 408 Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and developed factor analysis-based summary scores. Census-weighted norms were presented for English speakers, and sample-weighted norms were presented for Spanish speakers. Exploratory factor analysis for both English- and Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory factor analysis supported similar factor structures for English- and Sp...
This study examined the influence of Hispanic ethnicity and language/cultural background on perfo... more This study examined the influence of Hispanic ethnicity and language/cultural background on performance on the NIH Toolbox Cognition Battery (NIHTB-CB). Participants included healthy, primarily English-speaking Hispanic (n = 93; Hispanic-English), primarily Spanish-speaking Hispanic (n = 93; Hispanic-Spanish), and English speaking Non-Hispanic white (n = 93; NH white) adults matched on age, sex, and education levels. All participants were in the NIH Toolbox national norming project and completed the Fluid and Crystallized components of the NIHTB-CB. T-scores (demographically-unadjusted) were developed based on the current sample and were used in analyses. Spanish-speaking Hispanics performed worse than English-speaking Hispanics and NH whites on demographically unadjusted NIHTB-CB Fluid Composite scores (ps < .01). Results on individual measures comprising the Fluid Composite showed significant group differences on tests of executive inhibitory control (p = .001), processing spee...
Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected pe... more Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be...
There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (H... more There has been a reduction in the most severe cases of HIV-associated neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART). But the prevalence of milder forms of HAND still remains high. Data from systematically conducted studies on the effects of ART on cognition are scanty in India, where HIV-1 clade C is prevalent. The purpose of the present study was to assess the effect of antiretroviral therapy in HIV-seropositive (HIV+) individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and domain-specific levels of cognitive functioning were determined using a locally recruited normative sample, and a change in neurocognitive functioning at the 1-year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6 % of the HIV+ group at baseline. At the 1-year follow-up, the group showed significant improvement in the Learning domain (p < 0.05). HIV+ individuals showing improvement in the global cognitive scores had a signific...
Journal of acquired immune deficiency syndromes (1999), Jan 2, 2014
We tested our hypothesis that abdominal obesity when associated with increased levels of systemic... more We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Cross-sectional SETTING:: Six Academic Centers PARTICIPANTS:: 152 patients with plasma HIV RNA <1,000copies/ml had clinical evaluations and cognitive function quantified by global deficit scores (GDS). GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year of the index visit, GDS remained worse in patients with IL-6 levels in the high-versus-low tertile (p=0.02). Path an...
Journal of clinical and experimental neuropsychology, 2014
In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate ... more In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals' premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found that this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population. The Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants; a subset of 48 HIV+ individuals completed a second study visit (M = 14.4 months), in which the alternate version of the WRAT-4 was administered. Although HIV+ individuals evidenced worse current neur...
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Papers by Robert Heaton