Higher Cerebrospinal Fluid Soluble Urokinase-type Plasminogen Activator Receptor, But Not Interferon γ-inducible Protein 10, Correlate With Higher Working Memory Deficits.

BACKGROUND: We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S). METHODS: A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and ß2 microglobulin (ß2m) in the CSF and serum were quantified using different immunoassays. RESULTS: Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum ß2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and ß2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum ß2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024). DISCUSSION: We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.

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

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.

Characterization of HIV-Associated Neurocognitive Impairment in Middle-Aged and Older Persons With HIV in Lima, Peru.

Background: With widespread use of antiretroviral medications, people living with HIV (PWH) are living longer worldwide, increasing their risk of developing neurocognitive impairment (NCI). The proportion of Peruvians over age 60 is expected to increase to 25% of the population by 2050, including PWH. Therefore, the problem of aging and NCI, especially in the setting of HIV infection, is uniquely pressing. We sought to study the rates of and risk factors associated with NCI among middle-aged and older PWH in Lima, Peru. Materials and Methods: Sociodemographic, medical (infectious and non-infectious), and psychiatric comorbidity and laboratory data were collected. We administered a brief neuropsychological battery evaluating seven cognitive domains affected in HIV-associated NCI and a depression screening. Cognitive test raw scores were converted to T-scores that were demographically adjusted. Descriptive statistics were performed together with regression (unadjusted and adjusted) analyses to determine potential risk factors for NCI among PWH. Results: This was a cross-sectional study in which 144 PWH aged ≥40 years attending a large HIV clinic in Lima, Peru, were recruited from September 2019 to March 2020. Mean age was 51.6 ± 7.7 years, and mean years of education were 14.0 ± 3.1 with 15% females. Median [interquartile range (IQR)] current CD4 and nadir CD4 were 554 (371, 723) and 179 (83, 291), respectively, and 10% currently had AIDS. The prevalence of NCI was 28.5%, and many demonstrated difficulty with attention and working memory (70%). One-quarter of PWH had mild depression or worse on Patient Health Questionnaire 9 (PHQ-9 ≥ 5). In bivariate analyses, neither a depression history nor a higher PHQ-9 score correlated with NCI. No other non-communicable medical or psychiatric comorbidity nor HIV characteristic was predictive of NCI. Having a positive lifetime history of hepatitis B infection, pulmonary tuberculosis, or syphilis increased risk of NCI (PR 1.72; 95% CI 1.04-2.86) in unadjusted analyses, but not in adjusted analyses. Conclusions: NCI among older Peruvians with HIV was found to be highly prevalent with levels consistent with prior reports of HIV-associated NCI worldwide. Common latent HIV-associated co-infections, including latent syphilis, hepatitis B infection, or pulmonary tuberculosis, may increase the risk of NCI among middle-aged and older PWH in Peru.

Neurocognitive impairment in Spanish-speaking Latinos living with HIV in the US: Application of the neuropsychological norms for the US-Mexico border region in Spanish (NP-NUMBRS).

Objective Latinos in the US are at increased risk for HIV-associated neurocognitive impairment (NCI). Most studies of US Latinos living with HIV have included primarily English-speakers only. We investigated the rate, pattern, and correlates of HIV-associated NCI in native Spanish-speaking Latinos living in the US near the Mexican border. Methods Participants included 407 native Spanish-speaking Latinos (Age: M = 37.65, SD = 10.0; Education: M = 10.75, SD = 4.1; 53% male): 153 persons living with HIV (PLWH; 56% AIDS) and 254 healthy controls. All participants completed comprehensive neuropsychological assessments in Spanish. Raw neuropsychological test scores from seven domains were converted to demographically-adjusted T-scores using norms developed with healthy controls. Global and domain NCI were defined per established criteria. Among PLWH we applied norms developed for non-Hispanic (NH) Whites and Blacks, and investigated correlates of global NCI, including HIV disease characteristics and psychiatric comorbidities. Results Utilizing population specific norms, rates of global NCI were significantly higher among PLWH (39%) than healthy controls (17%), comparable to previously published rates. In contrast, rates of global NCI in the same group of PLWH were significantly different when NH White norms (63%, p < 0.0001) and NH Black norms were used (18%, p < 0.0001). Among PLWH without a history of lifetime substance use disorder, more years of antiretroviral exposure were significantly associated with decreased rates of global NCI. Conclusions Present findings lend support to the validity of newly developed norms for native Spanish-speakers living near the US-Mexico border, and underscore the importance of utilizing appropriate norms to accurately identify HIV-associated NCI.

Demographically-adjusted norms for the Grooved Pegboard and Finger Tapping tests in Spanish-speaking adults: Results from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project.

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

Demographically adjusted normative data for the Wisconsin Card Sorting Test-64 item: Results from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project.

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

Demographically adjusted normative data for the Halstead category test in a Spanish-speaking adult population: Results from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS).

OBJECTIVE: The present study aimed to develop norms applicable to Spanish-speakers living in the United States (U.S.)- Mexico border region for the Halstead Category Test (HCT), a test of executive function. METHODS: Healthy native Spanish-speakers (N = 252; Age: range 19-60 years, M = 37.28, SD = 10.24; Education: range 0-20 years; M = 10.65, SD = 4.33; 58.33% women) living in the U.S.-Mexico border region of California and Arizona completed the HCT as part of a comprehensive neuropsychological test battery. The univariable and interactive effects of demographic variables on HCT raw scores were examined. Total scores were normed using fractional polynomial equations, controlling for age, education, and gender. T-scores were also computed for HCT scores of the current Spanish-speaking normative sample using published, demographically-adjusted norms for English-speaking non-Hispanic Whites and Blacks. Impairment rates (T-Scores < 40) were calculated using published and current norms. RESULTS: Age was significantly associated with increased number of errors, and education and male gender were associated with decreased number of HCT errors (total raw scores). Applying norms developed for English-speaking non-Hispanic Whites and Blacks resulted in overestimation of impairment rates in the current sample (impairment: 48% with White norms and 27% with Black norms). This pattern was evident across levels of education except in participants with 13+ years of education, where rates of impairment using non-Hispanic Black norms were comparable to those based on newly developed norms. CONCLUSION: The present study presents norms for the HCT in a sample of U.S. Spanish-speakers, providing an important tool for identifying executive dysfunction in this population.

Neurocognitive impairment with hepatitis C and HIV co-infection in Southern Brazil.

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 infection groups compared with the uninfected control group, but no statistically significant differences among mono- and co-infected groups were found. HCV infection was associated with cognitive deficits, independently of liver dysfunction. HCV infection did not show an additive effect on neurocognitive function among HIV+. NCI was independent of HCV RNA on peripheral blood, CSF, and hepatic injury. While we did not find additive global effect, in the present study, there was some evidence of additive HIV/HCV co-infection effects in speed of information processing, executive function, and verbal fluency domains when comparing the co-infected group with the other three groups. NP impairment was not dependent on HCV subtypes.

Differences in Neurocognitive Impairment Among HIV-Infected Latinos in the United States.

OBJECTIVES: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. METHODS: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. RESULTS: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13-2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11-5.29; p=.03). CONCLUSIONS: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163-175).

Improving Detection of HIV-Associated Cognitive Impairment: Comparison of the International HIV Dementia Scale and a Brief Screening Battery.

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