Publications by authors named "Robert K Heaton"

270 Publications

Reduced Gut Microbiome Diversity in People With HIV Who Have Distal Neuropathic Pain.

J Pain 2021 Sep 13. Epub 2021 Sep 13.

Department of Pediatrics, University of California, San Diego, California.

Objective: Gut dysbiosis, defined as pathogenic alterations in the distribution and abundance of different microbial species, is associated with neuropathic pain in a variety of clinical conditions, but this has not been explored in the context of neuropathy in people with HIV (PWH).

Methods: We assessed gut microbial diversity and dysbiosis in PWH and people without HIV (PWoH), some of whom reported distal neuropathic pain (DNP). DNP was graded on a standardized, validated severity scale. The gut microbiome was characterized using 16S rRNA sequencing and diversity was assessed using phylogenetic tree construction. Songbird analysis (https://github.com/mortonjt/songbird) was used to produce a multinomial regression model predicting counts of specific microbial taxa through metadata covariate columns.

Results: Participants were 226 PWH and 101 PWoH, mean (SD) age 52.0 (13.5), 21.1% female, 54.7% men who have sex with men, 44.7% non-white. Among PWH, median (interquartile range, IQR) nadir and current CD4 were 174 (21, 302) and 618 (448, 822), respectively; 90% were virally suppressed on antiretroviral therapy. PWH and PWoH did not differ with respect to microbiome diversity as indexed by Faith's phylogenetic diversity (PD). More severe DNP was associated with lower alpha diversity as indexed by Faith's phylogenetic diversity in PWH (Spearman's ρ = .224, P = 0.0007), but not in PWoH (Spearman's ρ = .032, P = .748). These relationships were not confounded by demographics or disease factors. In addition, the log-ratio of features identified at the genus level as Blautia to Lachnospira was statistically significantly higher in PWH with DNP than in PWH without DNP (t-test, P = 1.01e-3). Furthermore, the log-ratio of Clostridium features to Lachnospira features also was higher in PWH with DNP than in those without (t-test, P = 6.24e-5).

Conclusions: Our results, in combination with previous findings in other neuropathic pain conditions, suggest that gut dysbiosis, particularly reductions in diversity and relative increases in the ratios of Blautia and Clostridium to Lachnospira, may contribute to prevalent DNP in PWH. Two candidate pathways for these associations, involving microbial pro-inflammatory components and microbially-produced anti-inflammatory short chain fatty acids, are discussed. Future studies might test interventions to re-establish a healthy gut microbiota and determine if this prevents or improves DNP.

Perspective: The association of neuropathic pain in people with HIV with reduced gut microbial diversity and dysbiosis raises the possibility that re-establishing a healthy gut microbiota might ameliorate neuropathic pain in HIV by reducing proinflammatory and increasing anti-inflammatory microbial products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpain.2021.08.006DOI Listing
September 2021

Influence of Educational Background, Childhood Socioeconomic Environment, and Language Use on Cognition among Spanish-Speaking Latinos Living Near the US-Mexico Border.

J Int Neuropsychol Soc 2021 Sep 6:1-15. Epub 2021 Sep 6.

Department of Psychiatry, HIV Neurobehavioral Research Program, University of California, San Diego, CA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617721001028DOI Listing
September 2021

The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid.

Viruses 2021 07 1;13(7). Epub 2021 Jul 1.

Division of Infectious Disease and Global Public Health, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

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 ( < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = -0.49, = 0.010), which was worst in the HIV+/METH+ group ( = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13071287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310127PMC
July 2021

Higher comorbidity burden predicts worsening neurocognitive trajectories in people with HIV.

Clin Infect Dis 2021 Jul 30. Epub 2021 Jul 30.

Department of Psychiatry, University of California, San Diego, UCSD HNRC, San Diego, CA, United States.

Background: Age-related comorbidities accumulate faster in people with HIV (PWH) than in those without (PWoH). We evaluated whether a validated multimorbidity scale, the Charlson Index, predicted neurocognitive trajectories in PWH.

Methods: Scaled scores a comprehensive neuropsychological battery were averaged across all visits. Multilevel modeling examined between- and within-person predictors of global neurocognition. At the between-person level, averaged Charlson scores were examined as a predictor of neurocognitive change rate, covarying for HIV disease characteristics. Within-persons, visit-specific Charlson Index was used to predict fluctuations in global neurocognition at the same and next visit, covarying for disease measures.

Results: Participants were 1195 PWH (mean baseline age 43·0; SD 9·7 years) followed for a mean of 7·1 years (range 0·5-20·5). At the between-person level, more rapid neurocognitive worsening correlated with higher (worse) average Charlson scores (standardized β -0·062, SE 0·015; p=0·001) and lower CD4 nadir (standardized β 0·055, SE 0·021; p=0·011), but not viral suppression or average CD4+ lymphocytes (ps > 0·05). At the within-person level, poorer visit-specific neurocognition was related to worse concurrent, but not preceding, Charlson scores (standardized β-0·046, SE 0·015; p = 0·003), detectable HIV viral load (standardized β0·018, SE 0·006; p = 0·001) and higher CD4+ (standardized β0·043, SE 0·009; p < 0·001).

Conclusion: The impact of comorbidities on neurocognitive decline exceeded that of HIV disease factors. Although correlative, the temporal relationships suggested that treatment of comorbidities might improve neurocognitive prognosis for PWH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab655DOI Listing
July 2021

Binge Drinking Relates to Worse Neurocognitive Functioning Among Adults Aging with HIV.

J Int Neuropsychol Soc 2021 Jul 26:1-11. Epub 2021 Jul 26.

UC San Diego, Department of Psychiatry, San Diego, CA, USA.

Objective: Given the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.

Method: Participants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.

Results: HIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).

Conclusions: Results showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617721000783DOI Listing
July 2021

Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV.

J Int Neuropsychol Soc 2021 07;27(6):661-672

Department of Psychiatry, University of California, San Diego, USA.

Objective: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.

Methods: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.

Results: HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).

Conclusions: Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617720001447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288448PMC
July 2021

Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV.

Mol Neurobiol 2021 Oct 30;58(10):4842-4855. Epub 2021 Jun 30.

Genomic Medicine Institute, Cleveland Clinic/Lerner Research Institute, 9500 Euclid Ave/Mail Code R4-008, Cleveland, OH, 44195, USA.

HIV-associated neurocognitive disorder (HAND) remains prevalent despite antiretroviral therapy and involves white matter damage in the brain. Although iron is essential for myelination and myelin maintenance/repair, its role in HAND is largely unexplored. We tested the hypotheses that cerebrospinal fluid (CSF) heavy-chain ferritin (Fth1) and transferrin, proteins integral to iron delivery and myelination, are associated with neurocognitive performance in people with HIV (PWH). Fth1, transferrin, and the pro-inflammatory cytokines TNF-α and IL-6 were quantified in CSF at baseline (entry) in 403 PWH from a prospective observational study who underwent serial, comprehensive neurocognitive assessments. Associations of Fth1 and transferrin with Global Deficit Score (GDS)-defined neurocognitive performance at baseline and 30-42 months of follow-up were evaluated by multivariable regression. While not associated with neurocognitive performance at baseline, higher baseline CSF Fth1 predicted significantly better neurocognitive performance over 30 months in all PWH (p < 0.05), in PWH aged < 50 at 30, 36, and 42 months (all p < 0.05), and in virally suppressed PWH at all three visit time-points (all p < 0.01). Higher CSF transferrin was associated with superior neurocognitive performance at all visits, primarily in viremic individuals (all p < 0.05). All associations persisted after adjustment for neuro-inflammation. In summary, higher CSF Fth1 is neuroprotective over prolonged follow-up in all and virally suppressed PWH, while higher CSF transferrin may be most neuroprotective during viremia. We speculate that higher CSF levels of these critical iron-delivery proteins support improved myelination and consequently, neurocognitive performance in PWH, providing a rationale for investigating their role in interventions to prevent and/or treat HAND.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-021-02433-7DOI Listing
October 2021

Measurement of Cognition for the National Children's Study.

Front Pediatr 2021 31;9:603126. Epub 2021 May 31.

Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

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 plan for measuring specific skills at different ages. Given the need for well-validated, direct behavioral measures of cognition that can be used in large-scale longitudinal studies, especially from birth to age 3 years, we also initiated three projects focused on the development of new measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.603126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200393PMC
May 2021

Mitochondrial DNA haplogroups and domain-specific neurocognitive performance in adults with HIV.

J Neurovirol 2021 Aug 8;27(4):557-567. Epub 2021 Jun 8.

Vanderbilt University Medical Center, Nashville, TN, USA.

Neurocognitive (NC) impairment (NCI) is an important cause of morbidity in persons with HIV (PWH). In the high-energy environment of the central nervous system, mitochondria contribute to neuroinflammation and aging, which may ultimately drive the pathogenesis of neurodegenerative diseases. Mitochondrial DNA (mtDNA) haplogroups are associated with health outcomes in PWH. For example, we previously observed less global NCI in Hispanic ancestry PWH having mtDNA haplogroup B. Another study reported increased NCI among PWH having African subhaplogroup L2a. We therefore analyzed NC domains in relation to these haplogroups in CNS HIV Antiretroviral Therapy Effects Research (CHARTER), a multi-site observational neuro-HIV study. Haplogroups were assigned using mtDNA sequence in 1016 PWH. Outcomes were NCI, defined by domain deficit score and mean T-scores (TS) for seven NC domains. Ancestry-stratified analyses of NC performance included Wilcoxon rank sum, χ, and Fisher's exact tests. Multivariable regression adjusted for NC comorbidity, antiretroviral therapy use, and nadir CD4 T cells. Among 98 Hispanic ancestry PWH, executive function, learning, and recall performance were better with haplogroup B (N = 17) than other haplogroups. With adjustment for covariates, haplogroup B remained associated with better executive function (p = 0.04) and recall TS (p = 0.03). PWH with haplogroup B had fewer impaired domains than other haplogroups (p < 0.01). Subhaplogroup L2a (N = 89) was associated with greater NCI in learning, recall, and working memory among 478 PWH of African ancestry, and had more impaired domains than other subhaplogroups (p < 0.01). These findings may inform risk stratification for NCI and studies to define mechanisms by which mtDNA variation may influence NCI in PWH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-021-00989-7DOI Listing
August 2021

Gut microbiota dysbiosis is associated with worse emotional states in HIV infection.

J Neurovirol 2021 04 2;27(2):228-238. Epub 2021 Mar 2.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV-) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV-) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = - 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-020-00933-1DOI Listing
April 2021

Apathy is associated with poorer abstinence self-efficacy in individuals with methamphetamine dependence.

Addict Behav Rep 2021 Jun 19;13:100331. Epub 2021 Jan 19.

University of California San Diego, School of Medicine, Department of Psychiatry, 220 Dickinson Street # B, San Diego, CA 92103, USA.

Background: Confidence in one's ability to achieve and maintain drug abstinence (i.e., abstinence self-efficacy) is a strong predictor of substance use treatment outcomes. Neurobehavioral factors that may interfere with abstinence self-efficacy are less well established, particularly in methamphetamine (METH). This study investigated whether apathy, which is highly prevalent during active METH use and periods of abstinence, influences abstinence self-efficacy among METH dependent individuals.

Methods: Sixty-six participants with lifetime METH dependence and METH abuse/METH dependence diagnoses within the last 18 months (mean age [SD] = 39.5 years [10.7]), and no severe psychiatric or neurological diseases, completed the Methamphetamine Self-Efficacy Scale (MSES), alongside a comprehensive neurobehavioral evaluation. The MSES presents six situations that may lead to relapse and collects self-report ratings for two subscales: "Confidence" (i.e., confidence in one's ability to abstain from using METH, or METH abstinence self-efficacy) and "Temptation" (i.e., how tempted one is to use METH) with regard to each situation. Apathy was measured using a composite -score comprised of items and scales from three well-validated, self-report assessments.

Results: Multivariable linear regression found that higher Apathy -scores were significantly associated with lower Confidence ratings (i.e., poorer METH abstinence self-efficacy;  < .05), independent of potentially relevant factors (e.g., Temptation to use METH, comorbid HIV disease, and neurocognitive impairment).

Conclusions: Elevated apathy may adversely impact one's confidence to abstain from METH use. Findings highlight the importance of addressing apathy in order to improve METH abstinence self-efficacy, which may subsequently increase the likelihood of successful METH treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abrep.2020.100331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820030PMC
June 2021

Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV.

J Neurovirol 2021 02 6;27(1):160-167. Epub 2021 Jan 6.

Department of Psychiatry, University of California, La Jolla, San Diego, CA, USA.

We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-020-00925-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284079PMC
February 2021

Updated demographically adjusted norms for the Brief Visuospatial Memory Test-revised and Hopkins Verbal Learning Test-revised in Spanish-speakers from the U.S.-Mexico border region: The NP-NUMBRS project.

Clin Neuropsychol 2021 02 30;35(2):374-395. Epub 2020 Dec 30.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

Objective: We generated demographically adjusted norms for the Brief Visuospatial Memory Test-revised (BVMT-R) and the Hopkins Verbal Learning Test-revised (HVLT-R) for Spanish-speakers from the U.S.-Mexico border region as part of a larger normative project. Healthy native Spanish-speakers ( = 203; Age: 19-60 years; Education: 0-20 years, 59% women) living in Arizona ( = 63) and California ( = 140) completed the BVMT-R and the HVLT-R as part of the larger Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project. Raw scores were converted to T-scores utilizing fractional polynomial equations, which considered linear and non-linear effects of demographic variables (age, education, sex). To demonstrate the benefit of employing our population-specific norms, we computed the proportion of our participants whose test performance fell below one standard deviation (T-score < 40) when applying published norms from non-Hispanic English-speakers, compared to the base rate derived from the new normative sample. The resulting demographically adjusted T-scores showed the expected psychometric properties and corrected the misclassification in rates of impairment that were obtained when applying norms based on the English-speaking sample. Unexpectedly, participants in Arizona obtained slightly lower HVLT-R T-scores than those in California. This site effect was not explained by available sociodemographic or language factors. Supplementary formulas were computed adjusting for site in addition to demographics. These updated norms improve accuracy in identification of learning and memory impairment among Spanish-speaking adults living in the U.S.-Mexico border region. It will be important to generate additional data for elders, as the present norms are only applicable to adults age 60 and younger.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1861329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218787PMC
February 2021

Sex Differences in the Patterns and Predictors of Cognitive Function in HIV.

Front Neurol 2020 23;11:551921. Epub 2020 Nov 23.

Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.

Despite advancements in antiretroviral therapy, mild cognitive deficits persist in nearly half of people with HIV (PWH). The profile of impairment in HIV is highly variable with deficits observed in a range of cognitive domains. Despite evidence of greater cognitive impairment among women with HIV (WWH) vs. men with HIV (MWH), it is unclear how MWH and WWH differ in the type of cognitive impairment and in risk factors associated with cognitive impairment profiles. In a large and well-characterized sample of PWH, we used machine learning to identify profiles of cognitive functioning and their associated factors overall and within sex. Participants included 1,666 PWH (201 WWH; 1,465 MMH) from the HIV Neurobehavioral Research Program who completed a neuropsychological test battery at their baseline visits. Using demographically-adjusted T-scores from 13 test outcomes assessing motor skills, executive functioning, attention/working memory, episodic learning and memory, verbal fluency, and processing speed, we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores (MCLUST R package). Random forest models were used to determine how sociodemographic (e.g., age, education), clinical (e.g., depressive symptoms, substance use disorder), and biological (e.g., HIV disease characteristics) factors differentially related to membership within a cognitive profile. All analyses were repeated within sex. Three cognitive profiles were identified overall and within each sex. Overall and within MWH, there were unimpaired and global weakness profiles. The third profile in the total sample demonstrated relatively weak auditory attention whereas in MWH showed relative strengths in attention and processing speed. Conversely, there was no unimpaired profile among WWH. Rather, WWH demonstrated separate profiles reflecting weakness in motor skills, a relative weakness in learning and delayed recall, and global weaknesses with spared recognition memory. Despite different cognitive profiles by sex, the most discriminative factors were similar between men and women and included reading level (cognitive reserve), current and nadir CD4 count, plasma HIV viral load, duration of HIV disease, age, depressive symptoms, and race/ethnicity. Findings fill a knowledge gap concerning sex differences in cognitive impairment in PWH and inform personalized risk reduction and therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.551921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732436PMC
November 2020

Social Isolation Is Linked to Inflammation in Aging People With HIV and Uninfected Individuals.

J Acquir Immune Defic Syndr 2021 04;86(5):600-606

Psychiatry; and.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933098PMC
April 2021

Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV.

Neurol Neuroimmunol Neuroinflamm 2020 11 14;7(6). Epub 2020 Oct 14.

From the Departments of Neurosciences and Psychiatry, University of California (R.J.E.), San Diego; Department of Psychiatry, University of California (D.J.M., E.E.S., R.K.H.), San Diego; Department of Medicine, University of California (S.M., T.H.), San Diego; Vanderbilt University (D.S., J.A.F.), Nashville, Tennessee; and Departments of Medicine and Psychiatry, University of California (S.L.L.), San Diego.

Objective: To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aβ-42, and elevated CSF total tau and neurofilament light (NFL).

Methods: This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusions included significant CNS confounding conditions. Measurements of total tau and Aβ-42 were performed by bead suspension array. NFL and 8-oxo-dG were measured using ELISA.

Results: Participants were 53 PWH, mean age 55 (±9.3) years, 19% women, and 48% non-Hispanic White. Higher 8-oxo-dG correlated with markers of AD-related neurodegeneration including lower CSF Aβ-42 (r = -0.34; = 0.012) and higher CSF NFL (r = 0.39; = 0.0091) and total tau (r = 0.6696; < 0.0001). Relationships remained after adjusting for demographic variables. Levels of protein carbonyls, a marker of protein oxidation, were not related to neurodegeneration markers.

Conclusions: Among virologically suppressed PWH, nucleic acid oxidation was associated with standard CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, mitochondrial dysfunction, and specific antiretroviral drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration.

Classification Of Evidence: This study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577534PMC
November 2020

Objective and subjective sleep measures are associated with neurocognition in aging adults with and without HIV.

Clin Neuropsychol 2020 Sep 30:1-20. Epub 2020 Sep 30.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

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. Eighty-five adults (PWH  = 52, HIV-negative  = 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. Objective and subjective sleep measures were unrelated ('s > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%,  = 0.05) and were more likely to be using prescription and/or over the counter sleep medication ( = 0.04). In the whole sample, better sleep efficiency ( < 0.01) and greater total sleep time ( = 0.05) were associated with better learning. Less sleep fragmentation was associated with better learning ( < 0.01) and recall ( = 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 ( < 0.01) and working memory ( = 0.05); this relationship was primarily driven by the HIV-negative group. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1824280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007669PMC
September 2020

Demographically adjusted norms for the Trail Making Test in native Spanish speakers: Results from the neuropsychological norms for the US-Mexico border region in Spanish (NP-NUMBRS) project.

Clin Neuropsychol 2021 02 27;35(2):308-323. Epub 2020 Sep 27.

Department of Psychiatry, HIV Neurobehavioral Research Program, University of California, San Diego, San Diego, CA, USA.

Objective: Despite the wide use of the Trail Making Test (TMT), there is a lack of normative data for Spanish speakers living in the USA. Here we describe the development of regional norms for the TMT for native Spanish speakers residing in the Southwest Mexico-Border Region of the USA.

Method: Participants were 252 healthy native Spanish speakers, 58% women, from ages 19 to 60, and ranging in education from 0 to 20 years, recruited in San Diego, CA and Tucson, AZ. All completed the TMT in Spanish along with a comprehensive neuropsychological test battery as part of their participation in the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project. Univariable and interactive effects of demographics on test performance were examined. T-scores were calculated using fractional polynomial equations to account for linear and any non-linear effects of age, education, and sex.

Results: Older age and lower education were associated with worse scores on both TMT A and B. No sex differences were found. The newly derived T-scores showed no association with demographic variables and displayed the expected 16% rates of impairment using a -1 cut point based on a normal distribution. By comparison, published norms for English-speaking non-Hispanic Whites applied to the current data yielded significantly higher impairment for both TMT A and B with more comparable rates using non-Hispanic African Americans norms.

Conclusions: Population-specific, demographically adjusted regional norms improve the utility and diagnostic accuracy of the TMT for use with native Spanish speakers in the US-Mexico Border region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1800099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240160PMC
February 2021

Daily Activities Related to Mobile Cognitive Performance in Middle-Aged and Older Adults: An Ecological Momentary Cognitive Assessment Study.

JMIR Mhealth Uhealth 2020 09 24;8(9):e19579. Epub 2020 Sep 24.

Department of Psychiatry, University of California San Diego, San Diego, CA, United States.

Background: Daily activities have been associated with neurocognitive performance. However, much of this research has used in-person neuropsychological testing that requires participants to travel to a laboratory or clinic, which may not always be feasible and does not allow for the examination of real-time relationships between cognition and behavior. Thus, there is a need to understand the real-time relationship between activities in the real world and neurocognitive functioning to improve tracking of symptoms or disease states and aid in the early identification of neurocognitive deficits among at-risk individuals.

Objective: We used a smartphone-based ecological momentary cognitive assessment (EMCA) platform to examine real-time relationships between daily activities and neurocognitive performance (executive functioning and verbal learning) in the everyday environment of middle-aged and older adults with and without HIV.

Methods: A total of 103 adults aged 50-74 years (67 persons with HIV; mean age 59 years, SD 6.4) were recruited from the University of California, San Diego HIV Neurobehavioral Research Program and the San Diego community. Participants completed our EMCA protocol for 14 days. Participants reported their current daily activities 4 times per day; following 2 of the 4 daily ecological momentary assessment (EMA) surveys, participants were administered the mobile Color-Word Interference Test (mCWIT) and mobile Verbal Learning Test (mVLT), each once per day. Activities were categorized into cognitively stimulating activities, passive leisure activities, and instrumental activities of daily living (IADLs). We used multilevel modeling to examine the same-survey and lagged within-person and between-person effects of each activity type on mobile cognitive performance.

Results: On average, participants completed 91% of the EMA surveys, 85% of the mCWIT trials, and 80% of the mVLT trials, and they reported engaging in cognitively stimulating activities on 17% of surveys, passive leisure activities on 33% of surveys, and IADLs on 20% of surveys. Adherence and activity percentages did not differ by HIV status. Within-persons, engagement in cognitively stimulating activities was associated with better mCWIT performance (β=-1.12; P=.007), whereas engagement in passive leisure activities was associated with worse mCWIT performance (β=.94; P=.005). There were no lagged associations. At the aggregate between-person level, a greater percentage of time spent in cognitively stimulating activities was associated with better mean mVLT performance (β=.07; P=.02), whereas a greater percentage of time spent in passive leisure activities was associated with worse mean mVLT performance (β=-.07; P=.01). IADLs were not associated with mCWIT or mVLT performance.

Conclusions: Smartphones present unique opportunities for assessing neurocognitive performance and behavior in middle-aged and older adults' own environment. Measurement of cognition and daily functioning outside of clinical settings may generate novel insights on the dynamic association of daily behaviors and neurocognitive performance and may add new dimensions to understanding the complexity of human behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/19579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545331PMC
September 2020

Lower CSF homovanillic acid relates to higher burden of neuroinflammation and depression in people with HIV disease.

Brain Behav Immun 2020 11 20;90:353-363. Epub 2020 Sep 20.

Department of Psychiatry, University of California, San Diego, HIV Neurobehavioral Research Program, San Diego, CA, USA; Department of Neurosciences, University of California, San Diego, San Diego, CA, USA.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544671PMC
November 2020

Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.

J Acquir Immune Defic Syndr 2020 12;85(5):617-625

Psychiatry, and.

Background: Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH).

Methods: We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time.

Results: At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease.

Conclusion: Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002484DOI Listing
December 2020

Both HIV and Tat expression decrease prepulse inhibition with further impairment by methamphetamine.

Prog Neuropsychopharmacol Biol Psychiatry 2021 03 4;106:110089. Epub 2020 Sep 4.

Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. Electronic address:

HIV infection and methamphetamine (METH) use are highly comorbid and represent a significant public health problem. Both conditions are known to negatively impact a variety of brain functions. One brain function that may be affected by HIV and METH use is sensorimotor gating, an automatic, pre-conscious filtering of sensory information that is thought to contribute to higher order cognitive processes. Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in both humans and animals, thereby enabling cross-species translational studies. While previous studies suggest HIV and METH may individually impair PPI, little research has been conducted on the effects of combined HIV and METH on PPI. The goal of this cross-species study was to determine the effects of METH on PPI in the inducible Tat (iTat) mouse model of HIV and in people with HIV. PPI was measured in the iTat mouse model before, during, and after chronic METH treatment and after Tat induction. Chronic METH treatment decreased PPI in male but not female mice. PPI normalized with cessation of METH. Inducing Tat expression decreased PPI in male but not in female mice. No interactions between chronic METH treatment and Tat expression were observed in mice. In humans, HIV was associated with decreased PPI in both men and women. Furthermore, PPI was lowest in people with HIV who also had a history of METH dependence. Overall, these results suggest HIV and METH may additively impair early information processing in humans, potentially affecting downstream cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pnpbp.2020.110089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750302PMC
March 2021

Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence.

Drug Alcohol Depend 2020 10 22;215:108245. Epub 2020 Aug 22.

Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, United States.

Background: Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; <50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the main and interactive (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS.

Methods: Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners' and the 5-Choice continuous performance tests (CPTs).

Results: METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance.

Conclusions: Recent methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drugalcdep.2020.108245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811354PMC
October 2020

Effects of HIV infection, antiretroviral therapy, and immune status on the speed of information processing and complex motor functions in adult Cameroonians.

Sci Rep 2020 08 20;10(1):14016. Epub 2020 Aug 20.

Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

HIV-associated neurocognitive deficits include impaired speed-of-information processing (SIP) and motor functions. There is lack of Cameroonian adult norms for assessing SIP or motor functions. This study of 683 Cameroonians (320 HIV+, 363 HIV-) establishes demographically-adjusted norms for six SIP [Wechsler-Adult-Intelligence-Scale (WAIS)-III Digit Symbol (WAIS-IIIDS) and Symbol Search (WAIS-IIISS), Stroop Color-Naming, Stroop Word-Reading, Trail-Making Test-A (TMT-A), Color Trails-1 (CTT1)], and two motor function [Grooved Pegboard-dominant (GP-DH) and non-dominant (GP-NDH) hands] tests. We assessed viral effects on SIP and motor functions. HIV-infected persons had significantly lower (worse) T scores on GP-DH, WAIS-IIIDS, Stroop Word-Reading, TMT-A; lower motor and SIP summary T scores. Significantly higher proportion of cases (20.7%) than controls (10.3%) had impaired SIP. Male cases had better T scores than female cases on GP-NDH, WAIS-IIIDS, WAIS-IIISS, TMT-A, CTT1; better SIP summary T scores. Antiretroviral therapy (ART) was associated with significantly better T scores on GP-NDH, WAIS-IIIDS, Stroop Color-Naming; better motor and SIP summary T scores. Cases with higher CD4 had better T scores on WAIS-IIIDS, TMT-A, CTT1; better SIP summary T scores. Overall, we demonstrate that HIV infection in Cameroon is associated with deficits in SIP and motor functions; ART and higher CD4 are associated with better cognitive performance. We provide SIP and psychomotor functions normative standards, which will be useful for neurobehavioral studies in Cameroon of diseases affecting the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-70981-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441321PMC
August 2020

Higher levels of plasma inflammation biomarkers are associated with depressed mood and quality of life in aging, virally suppressed men, but not women, with HIV.

Brain Behav Immun Health 2020 Aug 13;7:100121. Epub 2020 Aug 13.

University of California, San Diego, USA.

Background And Objectives: People with HIV (PWH) often suffer from depressive symptoms which have a deleterious impact on numerous domains including antiretroviral adherence and quality of life. In the general population, a treatment-resistant phenotype of depression is associated with systemic inflammation, which is of considerable importance as it responds favorably to anti-inflammatory medications. Aging PWH experience increasing inflammation. We sought to evaluate the impact of chronic inflammation in aging PWH on depressed mood.

Methods: PWH were recruited at 6 U.S. academic medical centers. Depressed mood was assessed using the Beck Depression Inventory (BDI)-II. Inflammatory biomarkers measured at the 12-year follow-up visit in blood plasma using immunoassays were neopterin, sTNFRII, d-dimer, IL-6, CRP, MCP-1, sCD14 and sCD40L. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers.

Results: Participants were 78 PWH, 14 (17.9%) women, 40 (51.3%) non-White, mean age 55.3 (±SD 8.29), with a nadir and current CD4 of 134 (IQR 36, 204) and 567 (316, 797), respectively. 80.5% were virally suppressed. A factor analysis of the eight inflammatory biomarkers in plasma at the 12-year follow-up visit yielded 3 Factors, with Factor 1 loading on neopterin and sTNFRII, Factor 2 loading on d-dimer, IL-6 and CRP, and Factor 3 loading on sCD40L (MCP-1 and sCD14 did not appear in any of the factors). Univariate regressions of each factor vs BDI-II scores yielded significance only for Factor 2 (r ​= ​0.295; p ​= ​0.0083 (Bonferroni-adjusted p ​= ​0.0261). Of the Factor 2 component biomarkers, BDI-II scores correlated significantly with d-dimer and IL-6, but not CRP. Women had worse BDI-II scores (p ​= ​0.0127). In a logistic regression with sex and Factor 2, both variables were significant (sex p ​= ​0.0246, Factor 2 p ​= ​0.0168). The relationship between Factor 2 and BDI was significant for men (r ​= ​0.348 [95% CI 0.111, 0.547]; p ​= ​0.0049), but not women (r ​= ​0.0580 95% CI -0.488, 0.571]; p ​= ​0.844). Viral suppression was not significant in the multivariate model.

Conclusions: Some PWH with depressed mood have elevated markers of inflammation in blood. Men showed this relationship, while women did not. Together with previous findings that an inflammatory depression phenotype responds to treatment with anti-inflammatory medications, our findings suggest that treatment with anti-inflammatory medications might benefit at least a subset of depressed PWH who have a high inflammatory biomarker profile, as well as poor response to antidepressant medications alone, and that the pathophysiology of depression in men and women with HIV may differ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbih.2020.100121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474567PMC
August 2020

The Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project: Overview and considerations for life span research and evidence-based practice.

Clin Neuropsychol 2021 02 29;35(2):466-480. Epub 2020 Jul 29.

Department of Psychiatry, University of California, San Diego, CA, USA.

Objective: This paper summarizes the findings of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project and offers a roadmap for future research.

Methods: The NP-NUMBRS project represents the largest and most comprehensive co-normed neuropsychological battery to date for native Spanish-speaking healthy adults from the U.S. (California/Arizona)-Mexico borderland region ( = 254; ages 19-60 years). These norms provide demographic adjustments for tests across numerous domains (i.e., verbal fluency, processing speed, attention/working memory, executive function, episodic memory [learning and delayed recall], visuospatial, and fine motor skills).

Conclusions: This project: 1) shows that the NP-NUMBRS norms consistently outperformed previously published norms for English-speaking non-Hispanic (White and African-American) adults in identifying impairment; 2) explores the role of Spanish-English bilingualism in test performance; and 3) provides support for the diagnostic validity of these norms in detecting HIV-associated neurocognitive impairment. Study limitations include the limited assessment of sociocultural variables and generalizability (e.g., other Latina/o populations, age limit [19 - 60 years]). Future research is needed to: 1) investigate these norms with U.S.-dwelling Spanish-speakers of non-Mexican heritage and other clinical subpopulations; 2) expand coverage of cognitive domains (e.g. language, visuospatial); 3) develop large normative datasets for children and older Latina/o populations; 4) examine how sociocultural factors impact performance (e.g., bilingualism, acculturation); 5) investigate these norms' diagnostic and ecological validity; and 6) develop norms for neurocognitive change across time. It is hoped that the NP-NUMBRS norms will aid researchers and clinicians working with U.S.-dwelling Spanish-speakers from the U.S.-Mexico borderland to conduct research and evidence-based neuropsychological evaluations in a more culturally responsive and ethical manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1794046DOI Listing
February 2021

Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV.

Ann Clin Transl Neurol 2020 07 3;7(7):1166-1173. Epub 2020 Jul 3.

Departments of Medicine and Psychiatry, University of California, San Diego, La Jolla, California.

Objective: Distal 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.

Methods: Ambulatory, 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.

Results: Of 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 pain. Baseline risk factors for incident pain included unemployment (OR [95% CI], 5.86 [1.97, 17.4]) and higher baseline body mass index (BMI) (1.78 [1.03, 3.19] per 10-units). Participants with neuropathic pain at follow-up had significantly worse QOL and greater dependence in activities of daily living than those who remained pain-free.

Interpretation: HIV DSP and neuropathic pain increased in prevalence and severity over 12 years despite high rates of viral suppression. The high burden of neuropathy included disability and poor life quality. However, substantial numbers remained pain-free despite clear evidence of neuropathy on exam. Protective factors included being employed and having a lower BMI. Implications for clinical practice include promotion of lifestyle changes affecting reversible risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359117PMC
July 2020

Cerebrospinal Fluid Norepinephrine and Neurocognition in HIV and Methamphetamine Dependence.

J Acquir Immune Defic Syndr 2020 10;85(2):e12-e22

Department of Psychiatry, University of California, San Diego, HIV Neurobehavioral Research Program, San Diego, CA; and.

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+/HIV-) and recent METH dependence (METH+/METH-), 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 HIV-/METH-, CSF NE was markedly elevated in the single risk-groups (HIV+/METH-: d = 0.96; HIV-/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 = -0.19), learning (r = -0.23), and delayed recall (r = -0.18). Similar relationships between higher NE and worse neurocognition were detected in the METH- groups (ie, HIV-/METH- and HIV+/METH-) and in the virally-suppressed persons HIV+ subgroup, but not in the METH+ groups (ie, HIV-/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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492443PMC
October 2020

Demographically-adjusted norms for selected tests of verbal fluency: Results from the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project.

Clin Neuropsychol 2021 02 4;35(2):269-292. Epub 2020 Jun 4.

Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.

Objective: Verbal fluency tests are sensitive to various disorders affecting the central nervous system and are commonly included in neuropsychological evaluations. We aimed to develop normative data for two verbal fluency tests in a sample of native Spanish-speakers living in the US-Mexico border region.

Method: Participants included 254 adults from the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) Project (Age: range = 19-60; Education: range = 0-20, 59% female). Participants completed two verbal fluency tests (i.e., letter [PMR] and semantic/category fluency [Animal Naming]) as part of a larger neuropsychological test battery. We examined linear and nonlinear effects of demographic factors (age, education, and gender) on verbal fluency raw scores, and developed T-scores using fractional polynomial equations controlling for demographics. We also calculated the rates of "impairment" (T-scores < 40) that would be obtained by applying the newly developed norms and available norms for non-Hispanic English-speakers on comparable tests.

Results: There were positive small effects of age and medium effects of education on verbal fluency raw scores. The normalized distribution of T-scores with the new norms showed expected psychometric properties. However, rates of impairment for both letter and semantic fluency were significantly higher when applying non-Hispanic White norms, and significantly lower when applying non-Hispanic Black norms.

Conclusions: We provide norms for Spanish-speakers living along the US-Mexico border region for two verbal fluency tests that are co-normed with a more extensive neuropsychological battery. These regional norms will improve interpretation of verbal fluency test performance in Spanish-speakers living in the US-Mexico borderland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1762931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819211PMC
February 2021

Introduction to the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) Project.

Clin Neuropsychol 2021 02 20;35(2):227-235. Epub 2020 May 20.

Department of Psychiatry, University of California San Diego, San Diego, California, USA.

Objective: The present introduction to the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project aims to provide an overview of the conceptual framework and rationale that guided the development of this project.

Methods: We describe important aspects of our conceptual framework, which was guided by some of the main purposes of neuropsychological testing, including the identification of underlying brain dysfunction, and the characterization of cognitive strengths and weakness relevant to everyday functioning. We also provide our rationale for focusing this norm development project on Spanish-speakers in the United States, and provide an outline of the articles included in this Special Issue focused on the NP-NUMBRS project.

Conclusions: The data presented in this Special Issue represent an important tool for clinicians and researchers working in the neuropsychological assessment of Spanish-speakers in the United States.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13854046.2020.1751882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150201PMC
February 2021
-->