Health disparities among African Americans (AAs) in the United States are evident, especially among older adults and people living with HIV (PLWH). These health disparities include worse cognitive functioning among AAs than White counterparts. Though disparities in health literacy among AAs impact health outcomes across clinical populations, less is known on the mechanistic role health literacy may play in explaining racial differences in cognitive functioning among older PLWH. The current study investigated the association between health literacy and global cognitive functioning among middle-aged and older AA and White adults with and without HIV in the Deep South.

Two hundred and seventy-three people (170 PLWH: 146 AA, 24 White; 103 HIV-negative: 67 AA, 36 White) were enrolled in an observational study and completed measures of sociodemographic characteristics, as well as the reading subtest of the Wide Range Achievement Test-3rd Edition to assess verbal IQ. A composite score of socioeconomic status (SES) was created using total years of education and annual household income. Neurocognitive functioning was assessed using a comprehensive cognitive battery (i.e., verbal, attention/working memory, executive function, learning, recall, speed of processing, and motor), from which a sample-based global Z-score composite was created. Health literacy was measured using a sample-based composite Z-score derived from the Rapid Estimate of Adult Literacy in Medicine, Test of Functional Health Literacy in Adults Reading Comprehension, Newest Vital Sign, and Expanded Numeracy Scale. First, multivariable linear regression analyses were performed within both PLWH and HIV-negative samples examining the association between race, SES, verbal IQ, and health literacy with cognitive functioning. These results informed two bootstrap confidence interval mediation analyses to determine whether health literacy mediated the association between race and global cognitive functioning.

In both PLWH and HIV-negative individuals, linear regressions showed that Whites had better global cognitive functioning, health literacy, and verbal IQ than AAs. Linear regressions showed that health literacy had an independent association with cognitive function when accounting for verbal IQ and SES. Mediations showed that health literacy significantly mediated the association between race and global cognitive functioning in both samples, independent of verbal IQ (PLWH: b = .07, 95% CI [0.0096, 0.2149]; HIV-negative: b = .15, 95% CI [0.0518, 0.2877]), indicating that Whites were expected to obtain higher global cognitive Z-scores than AAs in both PLWH and HIV-negative samples, through the mediating effect of better health literacy.

Health literacy significantly mediated the association between race and global cognitive functioning among middle-aged and older adults with and without HIV, underscoring the importance of health literacy in explaining racial disparities in cognitive outcomes among AAs in the Deep South. Findings have implications for guiding clinicians and healthcare providers in developing interventions that promote health literacy in these underserved populations, which may have downstream impacts on cognitive functioning. Future work is needed to examine mechanisms whereby health literacy impacts neurocognition among AA PLWH.

Approximately half of people living with HIV (PWH) experience HIV-associated neurocognitive disorders (HAND), yet HAND often goes undiagnosed. There is an ongoing need to find efficient, cost-effective ways to screen for HAND and monitor its progression in order to intervene earlier in its course and more effectively treat it. Prior studies that analyzed brief HAND screening tools have demonstrated that certain cognitive test pairs are sensitive to HAND cross-sectionally and outperform other screening tools such as the HIV Dementia Scale (HDS). However, few studies have examined optimal tests for longitudinal screening. This study aims to identify the best cognitive test pairs for detecting cognitive decline longitudinally.

Participants were HIV+ adults (N=132; ages 25-68; 59% men; 92% Black) from the Temple/Drexel Comprehensive NeuroHIV Center cohort. Participants were currently well treated (98% on cART, 92% with undetectable viral load, and mean current CD4 count=686). They completed comprehensive neurocognitive assessments longitudinally (328 total visits, average follow-up time=4.9 years). Eighteen participants (14% of the cohort) demonstrated significant cognitive decline, defined as a decline in global cognitive z-score of 0.5 (SD) or more. In receiver operating characteristic (ROC) analyses, tests with an area under the curve (AUC) of greater than .7 were included in subsequent test pair analyses. Further ROC analyses examined the sensitivity and specificity of each test pair in detecting significant cognitive decline. Results were compared with the predictive ability of the Modified HIV Dementia Scale (MHDS).

The following test pairs demonstrated the best balance between sensitivity and specificity in detecting global cognitive decline: Grooved Pegboard dominant hand (GPD) and category fluency (sensitivity=.89, specificity=.60, AUC=.75, p<.001), GPD and Coding (sensitivity=.76, specificity=.70, AUC=.73, p<.001), letter fluency and Trail Making Test (TMT) B (sensitivity=.82, specificity=.63, AUC=.73, p<.001), and GPD and TMT B (sensitivity=.81, specificity=.64, AUC=.73, p<.001). Change in MHDS predicted significant decline no better than chance (sensitivity=.61, specificity=.47, AUC=.53, p=.65).

Several cognitive test pairs, particularly those that include GPD, are sensitive to HIV-associated cognitive change, and far more sensitive and specific than the MHDS. Cognitive test pairs can serve as valid, rapid, cost-effective screening tools for detecting cognitive change in PWH, thereby better enabling early detection and intervention. Future research should validate the present findings in other cohorts and examine the implementation of test pair screenings in HIV care settings. Most of the optimal tests identified are consistent with the well-established impact of HAND on frontal-subcortical motor and executive networks. The utility of category fluency is somewhat unexpected as it places more demands on temporal semantic networks; future research should explore the factors driving this finding, such as the potential interaction of HIV with aging and neurodegenerative disease.

People with HIV (PWH) are at an increased risk for cognitive impairment as they age compared to their HIV-negative counterparts. Lifestyle factors can have protective effects on cognitive outcomes among PWH. However, little work has examined diet quality and cognitive function in PWH. Examining the association between diet quality and cognitive function among PWH is particularly important given this population’s increased risk for both poor diet quality and cognitive impairment. The purpose of this study was to examine the relationship between diet and cognitive function in aging PWH.

This cross-sectional study was conducted in Birmingham, Alabama and Cleveland, Ohio. Eighty-six PWH (mean age 56 years) completed standard triple-pass 24-hour diet recalls and a neurocognitive assessment. Partial Pearson’s correlations were conducted between diet variables and global neurocognitive function T scores, adjusting for total calories, sex, and education level.

Overall diet quality of the sample was poor. The overall sample presented with low Healthy Eating Index (HEI)-2015 scores, high glycemic index, twice the goal amount for saturated fatty acids (SFAs), and inadequate consumption of several nutrients typically associated with cognitive health including omega-3 fatty acids, dietary protein, fiber, Vitamin D, Zinc, and several B-vitamins. Greater total calories per day (r=0.28, p<0.05), greater percentage of total calories of SFAs (r=0.26, p<0.01), and lower glycemic index (r=-0.24, p<0.05) were associated with better cognition. Higher intake of several individual fatty acids, particularly SFAs, were associated with better cognition (correlations ranging from 0.23 to 0.31). Higher intakes of phosphorus (r=0.29, p<0.01), magnesium (r=0.25, p<0.05), and potassium (r=0.22, p<0.05) were associated with better cognition. Higher grams/day of several amino acids were associated with better cognition (correlations ranging from 0.22 to 0.27).

In a sample with overall poor diet quality not meeting recommended guidelines, findings suggest that being nourished in itself is associated with better cognitive function. Associations with several individual nutrients may inform potential intervention targets to protect brain health in PWH. Further, targeting food insecurity in interventions may have downstream effects on cognition in PWH.

The aim of the current longitudinal study was to use improved brain white matter integrity outcomes (better at resolving white matter complexity, hence with improved biological significance compared to traditional diffusion tensor imaging - DTI outcomes) while considering baseline age, cardiovascular diseases (CVD), and HIV disease markers impacts on the health of major white matter tracts in virally suppressed people Living with HIV infection (PLHIV) versus demographically, geographically, and life-style comparable HIVnegative controls. Furthermore, white-matter hyperintensity (WMH) and normal-appearing white matter (NAWM) volumes and microstructure were considered.

At baseline 48 HIV-controls and 84 virally suppressed PLHIV (mean age 55), and at 24-month follow-up, 40 HIV-controls and 75 virally suppressed PLHIV underwent an MRI scan (3T Phillips) collecting a high-resolution anatomical MRI, FLAIR, and a 32-direction diffusion imaging. The diffusion data were processed using mrtrix and intra-cranial volume-corrected outcomes included fibre density (FD), fibre cross-section (log was used; logFC) and a composite fibre density and cross-section (FDC). The volumetric data was first processed in Freesurfer 6.0, and WMH were segmented using the “pgs” U-Net neural network. Using mixed models, we examine the longitudinal mrtrix outcomes across major white matter tracts by HIV status, and associations with CVD (sum of the scaled scores of total cholesterol, HDL, Systolic BP, current smoking, and diabetes) and HIV disease (HIV duration, historical AIDS, nadir CD4, baseline CD4) markers. Additionally, we assessed the volume, and FDC in the periventricular and deep WMH, as well as NAWM, and the associations with CVD and HIV disease markers. We used FDR control procedure (alpha = 0.05), and all p-values reported are FDR adjusted.

Relative to controls, PLHIV showed significant reductions (p<.05 - p<.01) of FC, and FDC to a lesser extent, in multiple long cortical association tracts, and within striatal- and thalamic-frontoparietal connections. A small HIV by age interaction was only detected for FC of inferior longitudinal fasciculus (Beta = -0.004, SE = 0.002 p<.04). However, HIV duration (corrected for baseline age) was associated with worse FDC across multiple tracts (p<03 -p<.001). Baseline CD4 counts associated with lower FD in frontal association tracts (p<.05 -p<.005). Furthermore, WMH increased in size with time, age, and higher CVD risk factors, but not HIV status. In PLHIV, deep WMH and NAWM microstructure were both associated with worse CVD but not HIV disease markers.

The fine integrity of major white matter tracts is impacted by HIV status, HIV duration and baseline CD4, whereas WMH and NAWM volumes and microstructure are affected by CVD. Our study provides further evidence of the immuno-vascular underpinning of HIV neuropathogenesis in virally suppressed PLHIV. The convergence of these effects in aging PLHIV may lead to early neurodegeneration. Hence, improving CVD health and maintaining high CD4 is critical.

Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels

Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.

58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.

Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.

Rates of HIV are disproportionately high among Black individuals in the United States (CDC, 2020). Black individuals are at increased risk for neurocognitive impairment due to HIV (Marquine et al., 2016) and experience health disparities including increased morbidity and mortality (Asari, 2018; Manly et al., 1998). We sought to examine the relationship between perceived quality of healthcare and neuropsychological functioning among people living with HIV (PLWH) who identify as Black compared to those who are non-Black.

151 PLWH in the Los Angeles area (52% Black, age = 49.85 ± 10.54, education = 13.23 ± 2.11; 87% cisgender men, 8% cisgender women, 1% transgender men, 3% transgender women) completed comprehensive neuropsychological (NP) assessments (from which demographically-corrected domain and global T-scores were derived), psychiatric and sociodemographic interviews, and self-report questionnaires, including a measure of perceived healthcare quality (i.e., QUOTE-HIV). Statistical analyses included chi-square, t-test, ANOVA, and stepwise linear regression.

Only 14% of Black PLWH had private healthcare insurance (versus Medicare/Medicaid) compared to 33% of nonBlack PLWH (x2=11.33, p<.01). Black participants were significantly older than nonBlack participants (p<.01), but did not differ on gender, education, income, CD4 count, or HIV viral load. Younger Black participants (based on a median split for age; n = 23) reported the lowest perceived quality of healthcare (i.e., QUOTE-HIV total performance score), while older Black participants (n = 56) reported the highest perceived care (F = 3.80, p = .01), but the same relationship was not observed in nonBlack participants. In a stepwise multivariate regression model, including demographic and virological factors as well as healthcare quality, only household income and overall perceived healthcare quality (i.e., QUOTE-HIV total performance score) were significantly associated with Global NP T-scores among Black PLWH (R2=.12, F(1, 66)=4.46, p=.02).

When assessing healthcare quality and healthcare experiences among people living with HIV, race and age are important to consider. Private healthcare coverage may be less accessible to people of color, and in a multivariate model, only income and healthcare quality significantly predicted neuropsychological functioning in Black PLWH. When examining HIV and health outcomes, the complex relationships among quality of healthcare and health disparities, neuropsychological functioning, and structural racism warrant further investigation.

Even though the severity of HIV-associated neurocognitive disorders (HAND) has decreased with the introduction of combination antiretroviral therapy, mild forms of HAND remain prevalent. Many HIV-infected individuals live alone, so mild cognitive impairments are easily missed. It is important to check their neurocognitive and everyday functions during hospital visits; however, it is challenging for Japanese clinicians because many hospitals do not have enough clinical psychologists or neuropsychologists. Additionally, neuropsychological (NP) test results may not detect those mild cognitive impairments. A micro error has been given more attention as a new behavioral sign of the early stages of cognitive decline, especially among people with Mild Cognitive Impairment (MCI). The current study aimed to 1) develop a touch-panel HAND screening battery and 2) evaluate if the micro errors could differentiate individuals with HAND from their counterpart healthy individuals.

Forty HIV-infected men (age: 49.0±8.51 years old, education: 18.5±2.17 years) and 44 healthy men (age: 45.4±8.49 years old, education: 14.4±2.27 years) completed the touch-panel HAND screening battery which assessed six NP domains by seven subtests, everyday functions, and depression. A micro error is defined as a subtle action disruption or hesitation occurring immediately before making final actions. We evaluated the micro errors in short-term memory (STM) and long-term memory (LTM) of verbal learning tests (VLT).

Mann Whitney U tests revealed that the HIV+ group made significantly more micro errors on both STM (HIV+: 1.45±0.90 times, Healthy: 0.52±0.84 times) and LTM (HIV+: 1.85±0.73 times, Healthy: 1.29±0.71 times) than the healthy group (STM: W=1362, p< .001, Effect Size (EF)= .548; LTM: W=1199.5, p= .002, EF= .363). An independent samples T-test showed that the HAND group made significantly more micro errors than the non-HAND group (t=1.822, p= .038, ES= .595) on STM; moreover, the Asymptomatic Neurocognitive Impairment (ANI) group made significantly more micro errors than the healthy group (W=446, p< .001, ES= .689). On LTM, no significant micro error differences between HAND and non-HAND (W=184.5, p= .539, ES= -.189) nor between ANI and healthy group (W=327.5, p= .103, ES= .241) were found.

The present study suggests that a novel behavioral measure, micro errors, may be able to help detect even the mildest form of HAND, ANI. Given that the touch-panel HAND screening battery consists of NP and IADL tests, it is important to evaluate micro errors on these various measures. Additionally, the touch-panel screening battery requires minimal administrative staff involvement, which could be beneficial for busy HIV clinicians.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Human immunodeficiency virus (HIV) type 1 (HIV-1), cardiovascular disease, and HIV-associated neurocognitive disorders (HAND) disproportionately affect Black/African American individuals compared to other racial and ethnic groups. Understanding the mechanisms of cognitive health disparities is essential for developing policy and health interventions to combat such disparities. Cardiovascular risk factors/diseases are common comorbidities that likely contribute to cognitive health disparities among Black/African American people living with HIV (PWH), but their impacts on cognition longitudinally in this population are unclear. The current study examines the relationship between cardiovascular risk and cognitive functioning over time in Black/African American adults living with HIV.

A sample of 122 Black/African American adults with HIV (ages 25-68, M=51.8, SD=7.7; 98% on antiretroviral therapy; 91% with undetectable viral load) were selected from the Drexel/Temple Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core (CTRSC; based at Drexel University College of Medicine) Cohort. They completed longitudinal visits (300 total visits, average follow-up time=4.9 years) that included clinical interviews, medical record review, biometric measurements, and comprehensive neuropsychological assessments. Cardiovascular risk factors of interest were body mass index (BMI), waist-to-height ratio (WHtR), and a total vascular risk burden score (VBS) representing five risk factors: obesity, central obesity, diabetes, hyperlipidemia, and hypertension. Based on a prior principal component analysis, three cognitive domains were examined: (1) verbal fluency, (2) visual memory/visuoconstruction, and (3) motor speed/executive functions. Mixed models were used to examine domain-specific cognitive trajectories in relation to baseline cardiovascular risk factors and changes in cardiovascular risk factors.

Overall, cognitive test performance improved over time (p<.003). Baseline VBS was marginally associated with longitudinal change in verbal fluency (p=.06). Participants with low baseline VBS (0-1 risk factors) demonstrated improvement in verbal fluency (p=.002), while those with higher VBS (2-5 risk factors) demonstrated stability in verbal fluency. In contrast, greater increases in BMI and in WHtR predicted more favorable trajectories in motor speed/executive function (both p<.001). Patients with increasing BMI over time improved in this domain (p=.02), while patients with stable or decreasing BMI did not. A similar pattern was observed for WHtR change. No vascular risk factors were associated with trajectories of visual memory/visuoconstruction.

Higher total vascular risk burden was associated with less favorable verbal fluency trajectories, reflecting the negative cognitive consequences of disorders such as diabetes, hyperlipidemia, and hypertension. Unexpectedly, greater increases in BMI and WHtR were associated with more favorable trajectories in motor speed and executive functioning. In this population, weight gain may be a proxy for other positive health factors, such as immune reconstitution, which will be examined in future analyses. Taken together, cardiovascular risk factors have heterogeneous associations with cognitive trajectories, emphasizing the importance of examining the mechanisms of these varying relationships. Future research will examine how social determinants of health, such as racial/ethnic discrimination, contribute to disparities in cardiovascular risk factors and cognitive outcomes.

The prevalence of mild to moderate cognitive impairment, including episodic memory deficits, in people living with HIV (PLWH) remains high despite the life-extending success of antiretroviral pharmacotherapy. With PLWH now reaching near-normal life expectancy, questions concerning a potential synergy between age- and HIV disease-related effects, including degradation in fronto-limbic circuits, neural systems also compromised in Parkinson’s disease (PD), have emerged.

This cross-sectional study examined the similarities and differences in component processes of verbal episodic memory and their neural correlates in 42 PLWH, 41 individuals with PD, and 37 controls (CTRL) (all participants aged 45-79 years). Learning over five trials, short-delay (SD) and long-delay, (LD), free-recall (FR) and cued-recall (CR) indices were assessed using the California Verbal Learning Test-2. Retention scores for FR and CR were derived adjusting for Trial 5 performance. All memory scores were age- and education-corrected based on the control group and reported as Z-scores. Regional brain volumes were calculated using 3T MRI data and the SRI24 atlas to delineate frontal (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and limbic (hippocampus, thalamus) regions. Brain volumes were age- and head-sized corrected based on 238 controls (19-86 years old).

Compared with the CTRL group, the HIV and PD groups were impaired on learning across trials and on SD and LD free- and cued-recall, with no group difference between the HIV and PD groups on any score. All three groups benefited similarly from cues compared with free-recall. The HIV and PD groups did not differ from CTRL on retention scores. Regarding brain volumes, the HIV group had smaller middle frontal volumes than the PD or CTRL groups and smaller thalamic volumes than the PD group. Correlational analyses (Bonferroni correction for 8 comparisons, p<.01) indicated that fewer total number of words recalled on Trial 5, learning over Trials 1-5, total words recalled on SD-CR, LD-FR, and LD-CR were associated with smaller orbitofrontal volume in the HIV but not the PD group; the correlations between orbitofrontal volume and memory scores were significantly different between the HIV and PD groups. In PD, but not HIV, lower retention scores on SD-FR and LD-CR correlated to smaller hippocampal volume.

Impairment in learning and cued recall performance indicate that both encoding and retrieval processes are affected in PLWH and PD. Neural correlates of verbal memory differed between groups, with orbitofrontal volume associated with learning and recall in PLWH, whereas hippocampal volume was associated with retention scores in PD. Together, these results suggest that different nodes within the fronto-limbic mnemonic circuitry underlie the mutual verbal episodic memory deficits observed in older PLWH and PD. Support: AA023165, AA005965, AA107347, AA010723, NS07097, MH113406, and the Michael J. Fox Foundation for Parkinson’s Research

The Immigrant Health Paradox (IHP) suggests that immigrants have better health upon arrival in comparison to their U.S.-born Latinx counterparts, indicating that immigrants’ unique experiences may buffer against negative health outcomes, including cognition. Some studies indicate that IHP-related cognitive health benefits diminish with increased time spent in the U.S., while others suggest that this relationship may be age-dependent such that compared to migration during earlier or later life, migration during young/middle adulthood may be related to better cognition-potentially due to higher simultaneous cognitive demands associated with this age epoch (e.g., language acquisition, acculturation). However, this literature is equivocal and has methodological limitations (e.g., cognition typically assessed with cognitive screeners, lack of clinical populations) Thus, this study aimed to examine the role of age related to IHP and cognition within a well-characterized sample of HIV+ Latinx adults. It was hypothesized that compared to U.S.-born Latinx adults and those who immigrated earlier or later in life, the Latinx immigrant subgroup who migrated during young/middle adulthood would demonstrate better cognitive functioning.

This cross-sectional study included a HIV+ sample (A/=105) of 34 Latinx immigrants (Mage=45.56, SD=6.99) and 71 U.S.-born Latinx individuals (Mage=46.03, SD=7.63), who completed a comprehensive sociocultural questionnaire and cognitive battery. Demographically-adjusted average T-scores were computed for each cognitive test and domain (e.g., learning, memory). A series of Welch’s-corrected ANOVAS with post hoc Games-Howell tests for multiple comparisons were conducted to compare cognitive function across three groups: Latinx immigrants who migrated during earlier (<19 yrs) or later adulthood (>50 yrs), young/middle adulthood (20-49 yrs), and U.S.-born Latinx adults.

Compared to the other Latinx subgroups, Latinx immigrants who migrated during middle adulthood performed worse in Verbal Fluency (F(2,98)=8.04, p<.001), Attention/Working Memory (f(2,96)=6.10, p<.01), Executive Function (f(2,99)=5.11, p<.01), and Processing Speed (F(2,101)=3.36, p<.05). Posthoc Games-Howell tests showed that the mean Verbal Fluency (p<.01, 95% C.I.=[-21.37, -2.66]), Attention/Working Memory (p<.05, 95% C.I.=[-16.82, -1.59]), Executive Function (p<.01, 95% C.I.=[-14.66, -2.49]) and Processing Speed (p<.05, 95% C.I.=[-13.60, -1.31]) T-scores were significantly lower in Latinx immigrants who migrated in young/middle adulthood compared to the U.S.-born Latinx sample. Further, there were no differences between the U.S.-born Latinx group compared to the Latinx immigrant group who migrated earlier or later in life (ps>.05).

This preliminary study is the first to examine whether the potential protective cognitive effects of the IHP vary across the lifespan among Latinx immigrants with HIV, using a comprehensive neuropsychological battery. Age-related IHP benefits were not observed in this study. Moreover, Latinx immigrants who migrated during young/middle adulthood had worse cognitive functioning compared to their U.S.-born Latinx counterparts and those that migrated earlier or later in life. A possible explanation for this study’s unexpected findings is that the IHP is outdated due to the current sociopolitical climate immigrants experience compared to the 1980s when the theory was developed. Future studies, with larger samples, longitudinal designs, and greater sociocultural characterization (e.g., immigration reason/s, country of origin, discrimination), are needed to better understand the role of IHP in cognition.

Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamlines evaluation of neurocognitive functioning. Our group translated and culturally adapted the PennCNB for use among children and adolescents in this high-burden, low-resource setting. The current study examined the construct validity and sensitivity to HIV infection and exposure of the culturally adapted PennCNB among a cohort of HIV-affected children and adolescents in Gaborone, Botswana.

628 school-aged children aged 7-17 years (n=223 children living with HIV [HIV+]; n=204 HIV exposed, uninfected [HEU]; and 201 HIV unexposed, uninfected [HUU]) completed the PennCNB. Participants were recruited from a clinic specializing in the care and treatment of HIV+ children and adolescents in Gaborone, Botswana, as well as from local schools. Confirmatory factor analyses were performed on efficiency measures for 13 PennCNB tests. Multiple regressions examined associations between HIV and neurocognitive functioning while controlling for age and sex. Multivariate normative comparisons were used to examine rates of overall cognitive impairment by comparing individual profiles of test scores to the multivariate distribution of test scores using age-normed data from the HUU group.

Confirmatory factor analysis supported four hypothesized neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. As expected, there were main effects of age on cognitive performance across all domains (ps < .001), and there were small sex differences, with females performing better in executive functioning and males performing better on visuospatial processing. Children and adolescents living with HIV performed significantly worse than HUU across all domains (ps < .001), with the largest effect sizes on measures of abstraction, working memory, and processing speed. HEU also performed worse than HUU across several domains, with smaller effect sizes. Multivariate normative comparisons indicated that 27% of the HIV+ group evidenced global neurocognitive impairment.

Overall, results support the validity of a neurocognitive battery adapted for use in Botswana, a non-Western, resource-limited setting. Results indicated that the adapted battery applied to children and adolescents with limited computer familiarity had a similar factor structure as in Western settings, indicating that the PennCNB appeared to assess the hypothesized neurocognitive domains. Hypothesized associations with age and sex supported the battery’s construct validity. Moreover, the battery appears to be sensitive to cognitive impairments associated with perinatally-acquired HIV and in utero HIV-related exposures, as it discriminated between the HUU, HIV+, and HEU groups. Differences were found in specific domains and in detection of overall impairment, including approximately one quarter of children and adolescents living with HIV in this cohort evidencing global neurocognitive impairment. Together, these results provide evidence that the PennCNB could serve as a useful tool for the assessment of neurocognitive functioning in school-aged children and adolescents from Botswana and, potentially, other resource-limited settings.

PLWH report using cannabis for both recreational reasons and HIV symptom management (e.g., nausea, pain, depression/anxiety). Recent literature suggests that cannabis may attenuate HIV symptoms and neuroinflammation, which are strongly related to neurocognition. Additionally, older adults who are particularly vulnerable to cognitive impairment experience a decline in the endogenous cannabinoid system with age. Therefore, the aims of the present study were 1) to determine if cannabis use is associated with cognitive performance in PLWH, 2) to determine if age moderates the relationship between cannabis use and cognition in PLWH, and 3) to determine if there are differences in cognition in cannabis non-users, occasional users, and daily users among PLWH.

The sample included 225 PLWH (78% undetectable; 51% female, Mean age=49.10) who were classified as non-users (n=52), occasional users (n=53), or daily users (n=120). Cannabis use was measured via the Timeline Follow-back (TLFB). Cognition was examined using the NIH Toolbox Cognition Battery, which included measures of attention, working memory, executive function, processing speed, and episodic memory, as well as a fluid cognition composite score.

Increased frequency of cannabis use was weakly positively associated with episodic memory performance, r(224) = 0.15, p<0.05. Results of the multiple regression indicate that frequency of cannabis use was not significantly associated with any of the six cognitive domains. However, there was a significant interaction between age and cannabis use in the domains of attention (ß= 0.13, p < 0.05), working memory (ß= 0.12, p < 0.05), and episodic memory (ß= 0.15, p < 0.05), suggesting worse cognitive performance in older adults who use cannabis as compared to younger adults in this sample. When participants were grouped based on use status, there were no significant main effects of group.

After controlling for the effects of demographic factors and HIV disease severity, no significant negative associations between cannabis use and cognition were observed, suggesting that cannabis use is not related to cognitive impairment in PLWH. However, results were clarified by a significant interaction, indicating that older adults who use cannabis perform worse in the domains of attention, working memory, and episodic memory compared to younger adults, suggesting synergistic cognitive effects of age and cannabis use. We additionally found preliminary evidence for a potential positive effect of cannabis use on episodic memory in the overall sample. Future studies examining biological and behavioral mechanisms of improvement will be necessary to better examine this relationship.

Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.

HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.

Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.

In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.

A recent review called for a more robust assessment of cannabis use (CU), including amount and timing of recent use to assess neurocognitive effects of CU among people living with HIV (PWH) (Ellis et al., 2021). The current study addresses some issues raised by investigating between group neurocognitive differences among healthy controls and PWH who differ on their cannabis use histories, using strict inclusion criteria, robust classification of CU, and administration of an established neurocognitive test battery.

Among this community sample of adults (N=309), 58 were classified as CU+/HIV+ group (84.5% Male), 76 as CU-/HIV+ (57.9% M), 86 as CU+/HIV- (58.1% M), and 89 as CU-/HIV- (53.9% M). Exclusion criteria included history of past 12-month dependence and extensive lifetime dependence or significant use of illicit substances other than cannabis, severe or current mood or thought disorder, and other medical conditions that adversely impact neurocognitive functioning. Inclusion criteria for CU+ groups included <30-days since last CU, >10 times of CU in last month, 3 times of CU per month in last 12 months, > 1 year of CU, and > 500 times used in lifetime. CU parameters did not statistically differ between HIV+/CU+ and HIV-/CU+. CU- groups’ inclusion criteria required no CU in last 6 months, 196 lifetime number of times used, and no history of CU dependance. Lifetime CU did not statistically differ between CU-/HIV+ and CU-/HIV- groups. HIV+ groups did not differ significantly on HIV viral load in plasma or nadir CD4+ counts. Significant between group differences included age, sex, years of education, and amount of alcohol and nicotine use within 12 months. The aforementioned sociodemographic and substance use variables that differed between groups were covariates in analyses. A battery of 10 neurocognitive measures, two measures per each domain of learning, memory, motor, executive functioning, and processing speed. Global composite summary scores for overall neurocognitive performance were calculated by averaging M T-scores for each neurocognitive domain. Data transformations were used to address any violations of statistical assumptions.

To facilitate data reduction, neurocognitive task scores were standardized to T-scores using the M and SD of the CU-/HIV-group. An omnibus model of between-group comparisons on global neurocognitive task performance revealed no significant differences, F(3) = .16, p = .923. Subsequent Tukey’s post hoc test revealed no significant differences among the four groups. Results also revealed nonsignificant differences between groups in neurocognitive performance within each domain. However, the CU-/HIV- group performed significantly worse than the CU-/HIV+ group on the Executive Functioning domain, based on Tukey’s post hoc test.

We found no significant global neurocognitive differences among groups; however, there was some evidence for domain-specific neurocognitive differences in executive functioning. This contrasts somewhat with existing literature on HIV and cannabis-associated neurocognitive deficits. Several factors may have contributed to this, including our relatively healthy PWH sample. Future analyses will examine interactive effects of HIV severity and severity of CU on neurocognition. This analysis will better determine who, among PWH, are most at-risk for cannabis-associated neurocognitive effects and what factors may exacerbate them.

Global neurocognitive impairment (NCI) has been reported in white people living with HIV/AIDS (PLWHA) in 40%. In Latino populations there have been variable rates described from 30 to 77%. This variation has to do with the lack of normative data for Latino population and the application of norms for English-speakers, increasing the probability of misidentification of NCI. Thus, recognizing which are the best norms available for the Mexican population is important for the accurate identification of NCI. The aim of the present study was to investigate the rate and pattern of HIV associated neurocognitive impairment (NCI) and to compare rates of NCI between rates calculated using norms for the Latin-American population (NLAP) and norms for the US-Mexico border region (NP-NUMBRS).

CIOMS international ethical guidelines for the participation of human subjects in health research were followed. 82 PLWHA living in Tijuana (Mexico) participated in the study (Age: Mean=39.6, SD=10.9; 28.3% Female; Years of education: Mean=8.5, SD=3.6). PLWHA were recruited from the board-and-care home “Las Memorias” (73.4% on antiretroviral therapy; Years since HIV diagnosis: Mean=9.9, SD=7.1). Participants completed a neuropsychological test battery sensitive to detect HIV associated NCI that assessed four cognitive domains (verbal fluency, speed of information processing, executive function and learning/memory). Raw scores in these tests were transformed to percentiles using LAPN and transformed to T-scores using NP-NUMBRS. T-scores were averaged across tests to compute domain specific and global impairment scores. NCI was defined as percentile scores <16 and T-scores < 40. McNemar’s tests were used to compare the rate of NCI utilizing NLAP vs NP-NUMBRS.

According to NLAP, rates of global NCI were about 13.4%. Utilizing NP-NUMBRS rates of global NCI were about 34.1%. However, there is a positive and significant correlation between Global Neurocognitive Function score in PLWHA according to NLAP and NP-NUMBRS (r=0.66, p<.05). Rates of global NCI in PLWHA were significantly lower when using LAP norms (McNemar Chi-Square=29.89; p<.001). Regarding the pattern of NCI according both norms learning and memory was the most affected cognitive domain with 34% of impairment according to NLAP vs 51% of impairment according to NP-NUMBRs.

Utilizing NP-NUMBRS, rates of NCI are consistent with findings of prior studies. Employing norms for LAP the rates of NCI are lower that the ones reported in the literature. This is an important finding since PLWHA included in the sample have several vulnerable factors such as deportation, prostitution, drug abuse and discrimination for sexual preference, factor that could impact cognition. The pattern of neurocognitive function was also similar to those of prior studies in HIV. To accurately make NCI diagnosis it is important to use norms that consider specific characteristics of the population. The diagnosis of NCI is important since these deficits present a strong risk of concurrent problems in a wide range of health behaviors like medication non-adherence in PLWHA.

Olfactory dysfunction can influence nutritional intake, the detection of environmental hazards, and quality of life. Prior research has found discordance between subjective and objective measures of olfaction. In people living with HIV (PLWH), olfactory dysfunction is widely reported; however, few studies have examined concordance between subjective olfactory self-ratings and performance on an objective psychophysical measure of olfaction and associated factors in men living with HIV (MLWH).

MLWH (n=51, mean age=54 years, 66.7% Black) completed two subjective olfaction ratings (two 5-point Likert scales), the Smell Identification Test (SIT), cognitive measures (HVLT-R, TMT), and self-report questionnaires assessing smell habits, mood, cognitive failures, and quality of life. Participants were categorized into one of four groups: true positives (TP; impaired subjective olfaction and objective olfaction dysfunction), false negatives (FN; intact subjective olfaction and objective olfaction dysfunction), false positives (FP; impaired subjective olfaction and objective normosmia), and true negatives (TN; intact subjective olfaction and normosmia). Established formulas were used to calculate the sensitivity and specificity of subjective olfaction, and t-tests and ANOVA were used to examine potential demographic, clinical, and cognitive factors contributing to discordance between subjective and objective olfaction dysfunction.

Across both subjective self-report items, 35.3% reported olfactory dysfunction, whereas 60.8% had objective olfaction dysfunction on the SIT (score < 33). Black MLWH had significantly higher rates of subjective (Black 41.2% vs. White 35.3%) and objective (Black 73.5% vs. White 35.3%) olfactory dysfunction (X2(1)=9.22, p=.002). We found discordance between subjective and objective olfaction measures, with 29.4% of the sample having objective olfaction dysfunction and not recognizing it (FN). In comparison, 3.9% with self-rated olfaction impairment had normal objective olfaction scores (FP). Additionally, there was concordance in subjective self-reports compared with objective olfaction, with 35.3% correctly identifying normal olfaction (TN) and 31.4% correctly identifying olfactory dysfunction (TP). Those unaware of olfaction dysfunction (FN) reported using less scented products in daily life on the Smell Habits Questionnaire. Although the FN group had faster TMT scores, these findings were no longer significant after the removal of three outliers in the TP group (e.g., time to complete greater than 350 seconds).

Our findings cohere with work in healthy older adults, traumatic brain injury, and Parkinson’s disease, documenting that subjective olfaction may inadequately capture the full range of a person’s olfactory status. We extend these findings to a sample of MLWH, in which discordance rates ranged from 35-61% for subjective and objective olfactory dysfunction. Unawareness of olfactory dysfunction in MLWH was associated with less daily smell habits and paradoxically faster TMT performance. A higher number of smell habits in the TP group indicate that more frequent odor exposure may increase sensitivity to olfactory declines. Future studies with larger samples will be helpful in understanding the full nature of these relationships. Lastly, given that one-third of the sample had discordance between subjective and objective olfaction, objective olfaction measures may be useful to consider in the neuropsychological assessment and standard clinical care for PLWH.

Rapid automatized naming (RAN) assesses pre-literacy and could be useful for assessing the effects of HIV infection on the development of literacy. Many children with HIV live in sub-Saharan Africa, but the RAN has not been well-studied there. Cultural differences in when children learn color names and in how they prioritize between accuracy and speed can affect RAN results. Typically, RAN and other cognitive functions (e.g., general intelligence, processing speed, working memory, attention) are strongly related. Our goal is to examine how RAN performance relates to neurocognitive function in sub-Saharan Africa and whether RAN performance could reveal the effect of HIV on pre-literacy. The current study examines the relationship between RAN performance and cognitive variables in both children living with HIV (CLWH) and healthy controls in Tanzania.

486 children (ages 3-8) were administered RAN Color and Object tasks as part of a larger longitudinal study in Dar es Salaam, Tanzania. All participants were also administered the Leiter International Performance Scale - 3rd Edition (Leiter-3), a test of nonverbal intelligence and general cognitive function. Binomial logistic regression examined the likelihood of completing a RAN task and included age, Leiter-3 composite standard scores, and HIV status. Multiple linear regression using the same predictors assessed factors associated with RAN completion time in children who completed the tests. SES and education were not included in the model specifications because they were not correlated with any RAN measures.

Only 40% of children could complete the RAN Color task, while 88% completed the Object task. Logistic regression models showed that age (p<0.001), Leiter-3 Nonverbal IQ (p<0.01), and Processing Speed (p<0.001) composite scores were all unique predictors of whether children would complete the RAN Color task. Age (p <0.001) and Nonverbal IQ (p<0.001) were predictors of completing of the RAN Object task. Of those who could complete the RAN Color task, multiple linear regression demonstrated that age (p<0.01), Leiter-3 Nonverbal IQ (p=0.01) and Processing Speed (p=0.001) composites predicted completion time, with the model accounting for 25% of the variance. For the RAN Object task, multiple linear regression indicated age (p<0.001), Leiter-3 Processing Speed (p=0.01) and Nonverbal Memory (p=0.01) composites, and living with HIV (p=0.01), predicted completion time, with the model accounting for 42% of the variance.

Completion rates for RAN Color and Object tasks were low but improved with age. Consistent with brain maturation, increasing age and processing speed improved completion time, regardless of the RAN task. General cognitive ability predicted RAN Color performance, and Nonverbal Memory (encompassing attention, working memory, and retrieval) and HIV status additionally predicted RAN Object performance. Results extend research indicating RAN is distinct yet multifactorial, relying on various neurocognitive functions working together. Additionally, the relationship of HIV to RAN Object performance implies an overlap between the neurocognitive functions inherent in RAN and the neurocognitive weaknesses often reported in CLWH. These findings suggest cognitive vulnerabilities in CLWH may extend to literacy skills in sub-Saharan Africa, which requires further study.