Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.

We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.

Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.

Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

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.

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.