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People living with HIV are affected by the chronic consequences of neurocognitive impairment (NCI) despite antiretroviral therapies that suppress viral replication, improve health and extend life. Furthermore, viral suppression does not eliminate the virus, and remaining infected cells may continue to produce viral proteins that trigger neurodegeneration. Comorbidities such as diabetes mellitus are likely to contribute substantially to CNS injury in people living with HIV, and some components of antiretroviral therapy exert undesirable side effects on the nervous system. No treatment for HIV-associated NCI has been approved by the European Medicines Agency or the US Food and Drug Administration. Historically, roadblocks to developing effective treatments have included a limited understanding of the pathophysiology of HIV-associated NCI and heterogeneity in its clinical manifestations. This heterogeneity might reflect multiple underlying causes that differ among individuals, rather than a single unifying neuropathogenesis. Despite these complexities, accelerating discoveries in HIV neuropathogenesis are yielding potentially druggable targets, including excessive immune activation, metabolic alterations culminating in mitochondrial dysfunction, dysregulation of metal ion homeostasis and lysosomal function, and microbiome alterations. In addition to drug treatments, we also highlight the importance of non-pharmacological interventions. By revisiting mechanisms implicated in NCI and potential interventions addressing these mechanisms, we hope to supply reasons for optimism in people living with HIV affected by NCI and their care providers.

ObjectivesThis study investigates whether the year of arrival to the United States (U.S.) and birthplace relate to postmigration cognitive difficulties among foreign- and U.S.-born Arab Americans in later life.MethodsWe analyzed 19 years (2000-2019) of data from the American Community Survey Public Use Microdata Samples (weighted N = 393,501; ages ≥ 50 years). Cognitive difficulty was based on self-reported data, and weighted means, percentages, adjusted prevalence estimates, and adjusted odds ratio were calculated.ResultsControlling only for demographics, foreign-born Arabs reported higher odds of cognitive difficulty compared to U.S.-born Arabs across all arrival cohorts (p < .001). After accounting for economic and integration factors, those who arrived between 1991 and 2000 had higher odds (odds ratio [OR] = 1.06, 95% confidence interval [CI] =1.00, 1.19, p < .01), while those who arrived after 2001 had lower odds (OR = 0.87, 95% CI = 0.78, 0.97, p < .001) of cognitive difficulty. Lacking English proficiency (OR = 1.90, 95% CI = 1.82, 1.98, p < .001) was related to higher odds, whereas not being a U.S. citizen was significantly associated with lower odds (OR = 0.89, 95% CI = 0.52, 0.94, p < .001) of cognitive difficulty. Yet, results varied by birthplace. Migrants born in Iraq consistently reported the highest odds of cognitive difficulty across all arrival cohorts.DiscussionMigration history and birthplace may be important factors explaining cognitive disparities among the diverse group of Arab migrants and Arab Americans. Future research examining mechanisms underlying these associations and the impact of migration on cognitive health is needed to address cognitive disparities in migrants.

ObjectivesWe investigated the impact of culturally relevant social, educational, and language factors on cognitive test performance among Spanish speakers living near the US-Mexico border.MethodsParticipants 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.ResultsSeveral 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.ConclusionsDemographically 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.

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

ObjectivesIdentifying sociocultural correlates of neurocognitive dysfunction among Hispanics/Latinos, and their underlying biological pathways, is crucial for understanding disparities in Alzheimer's disease and related dementias. We examined cross-sectional associations between stress and neurocognition, and the role that metabolic syndrome (MetS) and systemic inflammation might play in these associations.MethodParticipants included 3,045 adults aged 45-75 (56% female, education 0-20+ years, 86% Spanish-speaking, 23% U.S.-born), enrolled in the Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study. Global neurocognition was the primary outcome and operationalized as the average of the z scores of measures of learning and memory, word fluency, and processing speed. Stress measures included self-report assessments of stress appraisal (perceived and acculturative stress) and exposure to chronic and traumatic stressors. MetS was defined via established criteria including waist circumference, high blood pressure, elevated triglycerides, fasting plasma glucose, and high levels of high-density lipoprotein cholesterol. Systemic inflammation was represented by high-sensitivity C-reactive protein (hs-CRP).ResultsSeparate survey multivariable linear regression models adjusting for covariates showed that higher perceived (b = -0.004, SE = 0.002, p < .05) and acculturative stress (b = -0.004, SE = 0.001, p < .0001) were significantly associated with worse global neurocognition, while lifetime exposure to traumatic stressors was associated with better global neurocognition (b = 0.034, SE = 0.009, p < .001). Neither MetS nor hs-CRP were notable pathways in the association between stress and neurocognition; rather, they were both independently associated with worse neurocognition in models including stress measures (ps < .05).DiscussionThese cross-sectional analyses suggest that stress appraisal, MetS, and systemic inflammation may be targets to reduce neurocognitive dysfunction among Hispanics/Latinos.

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

IntroductionDespite increased risk of cognitive decline in Hispanics/Latinos, research on early risk markers of Alzheimer's disease in this group is lacking. Subjective cognitive decline (SCD) may be an early risk marker of pathological aging. We investigated associations of SCD with objective cognition among a diverse sample of Hispanics/Latinos living in the United States.MethodsSCD was measured with the Everyday Cognition Short Form (ECog-12) and cognitive performance with a standardized battery in 6125 adults aged ≥ 50 years without mild cognitive impairment or dementia (x̄age  = 63.2 years, 54.5% women). Regression models interrogated associations of SCD with objective global, memory, and executive function scores.ResultsHigher SCD was associated with lower objective global (B = -0.16, SE = 0.01), memory (B = -0.13, SE = 0.02), and executive (B = -0.13, SE = 0.02, p's

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (

For people living with HIV (PLWH) and sexual minorities (SM), the intersection of identities can compound experiences like stigma and discrimination resulting in poor emotional health. We investigated the separate and interactive associations of HIV serostatus and sexual identity with emotional health. Our dataset included 371 participants. Emotional health was assessed by the NIH Toolbox emotion battery which yields negative affect, social satisfaction, and psychological well-being. Regressions were conducted for each composite, with HIV serostatus, sexual identity, and their interaction as independent variables along with covariates. The HIV serostatus x SM identity interaction was statistically significant in the regression of Negative Affect (p = .01): heterosexuals living with HIV had worse Negative Affect compared to heterosexual HIV-persons (p = .01). The interaction terms were for social satisfaction and psychological well-being were not significant. However, among PLWH, sexual minorities reported better Social Satisfaction (p = .03) and marginally better psychological well-being (p = .07) compared to heterosexuals.

The original version of this article unfortunately contained an error, and it has been corrected with this erratum. The original version of this article unfortunately contained and error. “In this article affiliations were incorrect: the affiliation for María J. Marquine should have been “Division of Geriatrics, Gerontology and Palliative Care, University of California, USA”; Sara Gianella, Genevieve Curtin, Susan J. Little, Scott L. Letendre “Department of Medicine, University of California San Diego, 9500 Gilman Drive MC 0679, La Jolla, CA 92093-0679, USA”. The original article has been corrected.

IntroductionAlthough subjective cognitive decline (SCD) may be an early risk marker of Alzheimer's Disease (AD), research on SCD among Hispanics/Latinos/as/x (henceforth Latinos/as) living in the U.S. is lacking. We investigated if the cross-sectional relationship of self-reported SCD with objective cognition varies as a function of ethnic background (Latinos/as versus Non-Hispanic Whites [NHWs]). Secondary analyses conducted solely within the Latino/a group investigated if informant reported SCD is associated with objective cognition and whether self-reported SCD is related to markers of brain health in a sub-sample of Latinos/as with available MRI data.MethodsEighty-three participants (≥60 years of age) without dementia (35 Latinos/as; 48 NHWs) completed the Mattis Dementia Rating Scale (MDRS) and the Subjective Cognitive Decline-Questionnaire (SCD-Q). Additionally, 22 Latino/a informants completed the informant-version of the SCD-Q. Hierarchical regression models investigated if ethnicity moderates the association of MDRS and SCD-Q scores after adjusting for demographics and depressive symptoms. Correlational analyses within the Latino/a group investigated self- and informant-reported associations of SCD-Q scores with objective cognition, and associations of self-reported SCD-Q scores with medial temporal lobe volume and thickness.ResultsLatinos/as had lower education and MDRS scores than NHWs. Higher SCD-Q scores were associated with lower MDRS scores only in Latinos/as. Within the Latino/a group, self, but not informant reported SCD was related to objective cognition. Medium to large effect sizes were found whereby higher self-reported SCD was associated with lower entorhinal cortex thickness and left hippocampal volume in Latinos/as.ConclusionsThe association of SCD and concurrent objectively measured global cognition varied by ethnic background and was only significant in Latinos/as. Self-reported SCD may be an indicator of cognitive and brain health in Latinos/as without dementia, prompting clinicians to monitor cognition. Future studies should explore if SCD predicts objective cognitive decline in diverse groups of Latinos/as living in the U.S.

ObjectiveOlder persons with human immunodeficiency virus (HIV) (PWH) are particularly susceptible to life-space restrictions. The aims of this study included: 1) using global positioning system (GPS) derived indicators as an assessment of time spent at home among older adults with and without HIV; 2) using ecological momentary assessment (EMA) to examine real-time relationships between life-space, mood (happiness, sadness, anxious), fatigue, and pain; and 3) determining if number of daily social interactions moderated the effect of life-space on mood.MethodsEighty-eight older adults (PWH n = 54, HIV-negative n = 34) completed smartphone-based EMA surveys assessing mood, fatigue, pain, and social interactions four times per day for two weeks. Participants' smartphones were GPS enabled throughout the study. Mixed-effects regression models analyzed concurrent and lagged associations among life-space and behavioral indicators of health.ResultsPWH spent more of their time at home (79% versus 70%, z = -2.08; p = 0.04) and reported lower mean happiness (3.2 versus 3.7; z = 2.63; p = 0.007) compared to HIV-negative participants. Controlling for covariates, more daily social interactions were associated with higher ratings of real-time happiness (b = 0.12; t = 5.61; df = 1087.9; p< 0.001). Similar findings were seen in lagged analyses: prior day social interactions (b = 0.15; t = 7.3; df = 1024.9; p < 0.0001) and HIV status (b = -0.48; t = -2.56; df = 1026.8; p = 0.01) attenuated the effect of prior day time spent at home on happiness.ConclusionAccounting for engagement in social interactions reduced the significant effect of time spent at home and lower happiness. Interventions targeting social isolation within the context of constricted life-space may be beneficial for increasing positive mood in older adults, and especially relevant to older PWH.

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (

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

ObjectiveThe 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.MethodsParticipants 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.ResultsOlder 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).ConclusionsThese 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.

ObjectiveThe 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.MethodsHealthy 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.ResultsAge 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.ConclusionThe 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.

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

ObjectiveThe 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.MethodsWe 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.ConclusionsThe 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.

ObjectiveThis 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.MethodsThe 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 (N = 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).ConclusionsThis 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.

Objective: The present review paper aimed to identify published neuropsychological test norms developed for Spanish-speakers living in the United States (U.S.). Methods: We conducted a systematic review of the literature via an electronic search on PubMed using keywords "Normative data," "Neuropsychological test," "norms", "Hispanic/Latinos," "Spanish Speakers," and "United States." We added other studies and published manuals as identified by citations in papers from the original search. Results Eighteen sources of normative data for Spanish-speakers in the U.S. were identified. Of the 18 citations identified, only four provide normative data on comprehensive batteries of tests for Spanish-Speakers. Two of these are based on persons living in the southwest of the U.S., who tend to be of Mexican origin. Overall, a number of the studies are focused on older persons and although the majority include participants with wide ranges of education, participants in the ends of the education distribution tend to be underrepresented. Conclusion: Here we provide a detailed description of the neuropsychological normative data currently available for Spanish-speakers living in the U.S. While there has been increased attention towards developing norms for neuropsychological batteries in Spanish-speaking countries (e.g., Latin America and Spain), there is still an urgent need to standardize neuropsychological tests among diverse groups of Spanish-speaking adults living in the U.S. The present review presents a list of norms for U.S.-dwelling Spanish-speakers, thus providing an important tool for clinicians and researchers.

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

ObjectiveThe Wechsler Adult Intelligence Scale (WAIS) processing speed subtests are among the most ubiquitous indices of processing speed in the field. The aim of this study was to develop and examine demographically-adjusted normative data for Spanish language versions of the WAIS-III Digit Symbol Coding (DSC) and Symbol Search (SS) subtests for US-dwelling Spanish-speakers living in the US/Mexico border region.MethodsThe sample included 203 healthy participants who were part of the larger Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project (DSC: n = 201; SS: n = 200).ResultsOlder age and higher education were both related to lower scores on the DSC and SS subtests (all ps  .05). Raw-to-scaled score conversions were calculated for both subtests, and fractional polynomial equations were derived to compute demographically-adjusted T-scores accounting for age, education, and gender for each subtest and the Processing Speed Index. Published norms for English-speaking non-Hispanic white adults slightly overestimated impairment rates (T-scores

ObjectiveWe 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.MethodParticipants 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

IntroductionEpisodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish-English Verbal Learning Test (B-SEVLT).MethodsThe target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds. Average age was 56.5 years ± 9.92, 54.5% were female, and mean education was 11.0 years ± 5.6 (unweighted n = 9309). Participants were administered the B-SEVLT in their preferred language (Spanish or English). Hispanic/Latino background adjusted B-SEVLT scores and percentile cut-points were created using survey-adjusted regression models.ResultsHigher educational attainment, younger age, and being female were associated with higher learning and memory performance. Hispanic/Latino background groups differed in B-SEVLT performance.DiscussionRepresentative learning and memory norms for Hispanic/Latinos of diverse backgrounds will improve cognitive assessment and accuracy of neurocognitive disorder diagnosis.

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.

Wisdom is a unique human personality trait with cognitive, affective or compassionate, and reflective dimensions. We evaluated relationships of three specific dimensions of wisdom with cognitive function and physical and mental well-being in people with HIV (PWH) and HIV-negative (HIV-) participants. Subjects included 138 adults (61 PWH, 77 HIV-) from the San Diego community. Validated measures were used to assess wisdom and well-being. Cognitive function was assessed via the Montreal Cognitive Assessment. We conducted multivariate linear regressions to evaluate the associations of wisdom dimensions with cognitive function and physical and mental well-being. Compared to the HIV- group, PWH had lower mean scores on cognitive function, and physical and mental well-being, and cognitive and reflective dimensions of wisdom, but similar scores on affective or compassionate wisdom. Among PWH, higher total wisdom scores were associated with older age, lower likelihood of substance dependence, greater mental well-being, better cognitive function, higher resilience, social support, and optimism scores, as well as lower levels of perceived stress and nadir CD4 count. Our findings of an association of different dimensions of wisdom with physical and/or mental well-being in PWH would point to a possibility that enhancing these dimensions of wisdom might improve health outcomes in PWH.

Metabolic syndrome (MetS), a constellation of related metabolic risk factors, is a common comorbidity associated with cognitive difficulty in people living with HIV (PLWH). Neurobehavioral disturbances (e.g., behavioral manifestations of frontal-subcortical dysfunction) are also prevalent in HIV, yet the role MetS might play in HIV-associated neurobehavioral disturbances is unknown. Thus, we examined the link between MetS and neurobehavioral disturbances in PLWH. Participants included 215 adults (117 PLWH, 98 HIV-uninfected), aged 36 to 65 years, from a cohort study at the University of California San Diego. Using the Frontal Systems Behavior Scale, we captured neurobehavioral disturbances (apathy, disinhibition, and executive dysfunction). MetS was defined by the National Cholesterol Education Program's Adult Treatment Panel-III criteria. Covariates examined included demographic, neurocognitive impairment, and psychiatric characteristics. When controlling for relevant covariates, both HIV serostatus and MetS were independently associated with greater apathy and executive dysfunction. HIV, but not MetS, was associated with greater disinhibition. The present findings suggest an additive effect of HIV and MetS on specific neurobehavioral disturbances (apathy and executive dysfunction), underscoring the importance of identifying and treating both HIV and MetS to lessen central nervous system burden among PLWH.

Little is known about the effects of aging-related conditions on health-related quality of life (HRQOL) among people living with HIV (PLWH). The purpose of our study was to examine the independent effects of neurocognitive impairment (NCI) and frailty and the interactive effects with HIV serostatus on HRQOL. Our sample consisted of 121 adults (63 PLWH and 58 HIV-uninfected) participating in the Multi-Dimensional Successful Aging among HIV-Infected Adults study at the University of California, San Diego. HRQOL was measured with the Medical Outcome Study 36-Item Short Form Health Survey scale. We found that frailty was significantly associated with HRQOL (p < .001) in the overall sample, and this effect was significantly stronger for PLWH than HIV-uninfected adults. NCI was not significantly associated with HRQOL in our sample. Frailty may be a particularly important factor in HRQOL for PLWH, highlighting the need for prevention and intervention strategies to mitigate the risks for frailty.

African Americans are disproportionately affected by HIV and socio-structural barriers that impact antiretroviral (ART) adherence. Two-way text-messaging interventions have shown promise in supporting adherence in US studies of mostly White people living with HIV (PLWH). However, culturally-appropriate tailoring is necessary to maximize intervention effectiveness among other racial/ethnic groups. Thus, to refine an existing text-messaging intervention, we examined barriers and facilitators to ART adherence among African Americans and perspectives on features to integrate into the extant intervention. Three focus groups, two with African American PLWH (n = 5 and n = 7) and one with providers of care (n = 11) were conducted; transcripts of audio-recordings were thematically analyzed. Adherence supports operated at individual, interpersonal, and structural/environmental levels (e.g., using reminders and pill organizers, wanting to protect partners from HIV, and positive interactions with providers). Adherence barriers also operated at multiple ecological levels (e.g., poor mental health, fear of disclosure of HIV status, and unstable housing). Participant-suggested features for refinement included: i) matching content to participants' comfort with receiving messages referencing HIV or medication-taking, ii) culturally-tailoring content for African Americans, iii) tracking adherence, and iv) encouraging adherence interactions between patients and providers. Feedback from both patients and providers is foundational to designing effective ART interventions among African American PLWH.

Frailty is a geriatric condition characterized by increased vulnerability to physical impairments and limitations that may lead to disabilities and mortality. Although studies in the general population suggest that psychosocial factors affect frailty, less is known about whether similar associations exist among people living with HIV (PLWH). The purpose of this study was to examine psychosocial correlates of frailty among PLWH and HIV-uninfected adults. Our sample included 127 adults (51% PLWH) participating in the Multi-Dimensional Successful Aging among HIV-Infected Adults study at the University of California San Diego (average age 51 years, 80% male, 53% White). Frailty was assessed via the Fried Frailty Index. Psychosocial variables significant in bivariate models were included in principal component analysis to generate factor variables summarizing psychosocial correlates. Multivariate logistic regression models were fit to examine the independent effects of factor variables and their interaction terms with HIV status. In bivariate models, frailty was associated with multiple psychosocial variables, for example, grit, optimism, personal mastery, social support, emotional support. Factor analysis revealed that psychosocial variables loaded on two factors-Positive Resources/Outlook and Support by Others. The multivariate model showed significant main effects of Support by Others and HIV status, and interactive effects HIV X Positive Resources/Outlook, such that Positive Resources/Outlook was negatively associated with frailty for PLWH but not for HIV-uninfected individuals. These analyses indicate that psychosocial factors may be associated with frailty among PLWH. Positive resources and outlook may play a role in frailty prevention. Future longitudinal studies are needed to establish causal links.

BackgroundThe adverse consequences of HIV and related comorbidities on the central nervous system remain prevalent in the era of combination antiretroviral therapy. Metabolic syndrome (MetS) is a common comorbidity in HIV and has been linked to increased neurocognitive impairment in the general population. We investigated the association between MetS and neurocognition among persons living with HIV (PLHIV).MethodsParticipants included 109 PLHIV and 92 HIV-uninfected adults (HIV-) from the Multi-dimensional Successful Aging cohort study at the University of California San Diego (age: M = 50.8, SD = 8.0). Participants completed neuromedical, psychiatric, and neurocognitive assessments. Based on a comprehensive neurocognitive battery, we examined global neurocognitive deficits (based on the entire battery) and neurocognitive deficits in 7 domains (verbal fluency, learning, recall, executive function, working memory, speed of information processing, and fine motor skills). MetS was determined via the standard criteria by the National Cholesterol Education Program's Adult Treatment Panel-III. Covariates examined included demographics and psychiatric comorbidities (and HIV disease characteristics among PLHIV).ResultsMetS had an independent significant effect on global neurocognitive deficits among PLHIV (P = 0.03) but not among their HIV- counterparts (P = 0.93). Among PLHIV, MetS was most strongly associated with the neurocognitive domains of learning, fine motor skills, and executive function. Diabetes and elevated triglycerides were the MetS components most strongly linked with increased global neurocognitive deficits in PLHIV.ConclusionsThe present findings underscore the need for early identification of PLHIV at risk for MetS and the implementation of preventive and treatment approaches to lessen the development of MetS and neurocognitive impairment among PLHIV.

Neuroinflammation is a common pathological correlate of HIV-associated neurocognitive disorders (HAND) in individuals on antiretroviral therapy (ART). Triggering receptor expressed on myeloid cells 2 (TREM2) regulates neuroinflammation, clears extracellular Amyloid (A)-β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM2 has not been studied in HIV+ brain tissues. In this retrospective study, we investigated TREM2 expression levels and localization to microglia, Aβ protein levels, and tumor necrosis factor (TNF)-α transcript levels in the frontal cortices of 52 HIV+ decedents. All donors had been on ART; 14 were cognitively normal (CN), 17 had an asymptomatic neurocognitive impairment (ANI), and 21 had a minor neurocognitive disorder (MND). Total TREM2 protein levels were increased in the soluble and decreased in the membrane-enriched fractions of MND brain tissues compared to CN; however, brains from MND Hispanics showed the most robust alterations in TREM2 as well as significantly increased TNF-α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM2 protein and transcripts for TNF-α were not observed in non-Hispanics, despite higher levels of Aβ in the non-Hispanic CN group compared to the non-Hispanic MND groups. These findings show that decreased and increased TREM2 in membrane-bound fractions and in soluble-enriched fractions, respectively, is associated with increased Aβ and neuroinflammation in this cohort of HIV+ brains, particularly those identifying as Hispanics. These findings suggest a role for TREM2 in the brain of HIV+ individuals may deserve more investigation as a biomarker for HAND and as a possible therapeutic target. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

The Veterans Aging Cohort Study (VACS) Index is a composite marker of multisystem injury among HIV-infected persons. We aimed to examine its cross-sectional association with functional outcomes, after considering neurocognitive impairment (NCI) and other well-established correlates of everyday functioning among HIV-infected persons. Participants included 670 HIV-infected adults (ages 18-76; 88% male; 63% non-Hispanic White; median current CD4 = 404 cells/mm3; 67% on antiretroviral therapy; AIDS = 63%) enrolled in observational studies at the University of California San Diego HIV Neurobehavioral Research Program. Functional outcomes were assessed via self-report measures of declines in activities of daily living, perceived cognitive symptoms in daily life, and employment status. NCI was assessed via a comprehensive neurocognitive test battery and defined based on established methods. Covariates examined included demographics, HIV disease characteristics not included in the VACS Index, and psychiatric comorbidities. The VACS Index was computed via standard methods and categorized based on its distribution. Results from multivariable regression models showed that both higher VACS Index scores (indicative of worse health) and the presence of NCI were independently associated with declines in activities of daily living, increased cognitive symptoms in daily life, and unemployment. These independent effects remained after adjusting for significant covariates. In conclusion, the VACS Index may be a useful tool for identifying HIV-infected patients at high risk for everyday functioning problems. Considering factors such as NCI, historical HIV disease characteristics, and current mood might be particularly important to enhance the predictive power of the VACS Index for functional status among HIV-infected persons.

Grit and ambition are psychological factors that may protect neurocognitive function among persons living with HIV (PLWH). We examined associations between grit, ambition, premorbid verbal intellectual function, and current neurocognitive and everyday functioning among PLWH and persons without HIV (HIV-). 120 PLWH and 94 HIV- adults completed the Grit Scale (includes total score and consistency of interests and perseverance of effort subscales), ambition scale, and a comprehensive neurobehavioral battery. PLWH had lower grit scores than HIV- adults. The two groups did not differ on ambition. No relationship was observed between grit and cognition among HIV- adults. Among PLWH, however, higher perseverance of effort and more ambition was related to better global neurocognitive functioning, and higher grit, but not ambition, was related to independence in daily functioning. Longitudinal studies are needed to elucidate these relationships over time and examine whether grit or ambition have protective effects on cognitive outcomes among PLWH.

Background: A lack of high-quality provider education hinders the delivery of standard-of-care delirium detection and prevention practices in the intensive care unit (ICU). To fill this gap, we developed and validated an e-learning ICU Delirium Playbook consisting of eight videos and a 44-question knowledge assessment quiz. Given the increasing Spanish-speaking population worldwide, we translated and cross-culturally adapted the playbook from English into Spanish. Objective: To translate and culturally adapt the ICU Delirium Playbook into Spanish, the second most common native language worldwide. Methods: The translation and cross-cultural adaptation process included double forward and back translations and harmonization by a 14-person interdisciplinary team of ICU nurses and physicians, delirium experts, methodologists, medical interpreters, and bilingual professionals representing many Spanish-speaking global regions. After a preeducation quiz, a nurse focus group completed the playbook videos and posteducation quiz, followed by a semistructured interview. Results: The ICU Delirium Playbook: Spanish Version maintained conceptual equivalence to the English version. Focus group participants posted mean (standard deviation) pre- and post-playbook scores of 63% (10%) and 78% (12%), with a 15% (11%) pre–post improvement (P = 0.01). Participants reported improved perceived competency in performing the Confusion Assessment Method for the ICU and provided positive feedback regarding the playbook. Conclusion: After translation and cultural adaptation, the ICU Delirium Playbook: Spanish Version yielded significant knowledge assessment improvements and positive feedback. The Spanish playbook is now available for public dissemination. [ABSTRACT FROM AUTHOR]

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

Higher levels of physical activity (PA) have been linked to better neurocognitive functioning in many populations. The current study examines the longitudinal association between PA and neurocognitive functioning among HIV-infected and HIV-uninfected persons. Community-dwelling adults (N = 291) self-reported level of PA and completed a comprehensive neuropsychological battery at two to four study visits (Mean follow-up time = 2.6 years). Participants were divided into three PA groups: "No PA" (no PA at any visit), "consistent PA" (PA at ≥50% of visits), and "inconsistent PA" (PA

ObjectivesHuman 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.MethodsParticipants 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.ResultsCompared 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

ObjectiveTo identify key mood, social, and functional correlates of current participation in mental health treatment and barriers to participation in mental health treatment among older HIV infected (HIV+) veterans.MethodsHIV+ veterans (N = 150) aged ≥ 50 years receiving HIV-related medical care at the VA San Diego Healthcare System, San Diego, California, anonymously completed a survey assessing current self-reported mood, social support, daily functioning problems, mental health service utilization, and barriers to participating in mental health services. Veterans also completed the 2-item Patient Health Questionnaire (PHQ-2), a validated depression screening instrument frequently used in primary care settings. Data were collected from February 2014 to May 2014.ResultsOverall, 44% of participants screened positive for depressive symptomatology on the PHQ-2; 55% of those who screened positive were participating in mental health treatment. Of the 45% of veterans who screened positive on the PHQ-2 and were not in treatment, two-thirds (66%) stated they had been offered services; however, they were not engaging in or accepting the services. Regardless of PHQ-2 status, current self-reported depressive symptoms emerged as an independent, significant positive predictor of participation in mental health treatment (odds ratio = 5.98; 95% CI, 1.16-30.72; P = .03), whereas anxiety, HIV-related stigma, sufficiency of social support, and daily functioning problems were not associated with mental health treatment utilization. Primary reported barriers to mental health treatment included scheduling/availability, travel time and transportation, and discomfort with group settings.ConclusionsResults of this study suggest there may be a need to better engage older HIV+ veterans in depression-related treatment. The use of telehealth technology, such as teletherapy, electronic devices, and cell phone-based programs, may be beneficial in helping older HIV+ veterans overcome many barriers that restrict their participation in mental health treatment.

BackgroundThe Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immunodeficiency virus (HIV)-infected persons, has been associated with concurrent risk for neurocognitive impairment (NCI). The present study examined whether the VACS Index predicts longitudinal neurocognitive change.MethodsParticipants included 655 HIV-infected persons followed for up to 6 years in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (mean age at baseline, 42.5 years; 83% male; 60% white; AIDS in 67%; median current CD4(+) T-cell count, 346/μL; 61% receiving antiretroviral therapy). The VACS Index was calculated through standard methods. Participants completed a comprehensive neurocognitive battery. Neurocognitive status was plotted over time using demographically and practice-adjusted global and domain T scores. NCI was defined by global deficit scores derived from T scores.ResultsBaseline VACS Index scores were not predictive of changes in global T scores during the follow-up period (P = .14). However, in time-dependent analyses adjusting for covariates, higher VACS Index scores were significantly associated with worse global and domain neurocognitive performance (Ps < .01), as well as increased risk for developing NCI in a subgroup of persons who were neurocognitively normal at baseline (hazard ratio [HR], 1.17; P < .001). We categorized VACS Index scores by quartiles and found that the upper-quartile group was significantly more likely to develop NCI than the lower quartile (HR, 2.16; P < .01) and middle groups (HR, 1.76; P < .01).ConclusionsChanges in VACS Index scores correspond to changes in neurocognitive function. HIV-infected persons with high VACS Index scores are at increased risk for decline and incident NCI. The VACS Index shows promise as a tool for identifying HIV-infected persons at risk for NCI.