The impacts of HIV infection, age, and education on functional brain networks in adults with HIV.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in people with HIV (PWH). Studies suggested that certain sociodemographic factors are associated with the risk of HAND in PWH. Here we investigated the impact of HIV infection and demographics on functional brain networks. One run of 8.5 min resting state functional MRI (fMRI) data was collected from 101 PWH (41-70 years old) and 40 demographically comparable controls. Functional connectivity (FC) was calculated using average wavelet coherence. The impact of demographic factors on FCs was investigated using canonical correlation analysis (CCA). Wavelet coherence analysis revealed a reduced within-network connectivity in the dorsal somatomotor network (dSMN), along with a reduced between-network connectivity between dSMN and medial temporal lobe (MTL) in PWH (compared to controls). Across all participants, CCA revealed that older age and HIV infection had negative impacts on network connectivity measures (mainly reduced within- and between-network FCs), whereas education had an opposite effect. In addition, being female at birth or a member of a minority ethnic/racial group was also associated with network disruptions. Our data suggested that advanced age and HIV infection are risk factors for functional brain network disruptions, whereas higher educational attainment was linked to better preserved functional network connectivity.

Connectome-based prediction of global cognitive performance in people with HIV.

Global cognitive performance plays an important role in the diagnosis of HIV-associated neurocognitive disorders (HAND), yet to date, there is no simple way to measure global cognitive performance in people with HIV (PWH). Here, we performed connectome-based predictive modeling (CPM) to pursue a neural biomarker of global cognitive performance in PWH based on whole-brain resting-state functional connectivity. We built a CPM model that successfully predicted individual differences in global cognitive performance in the training set of 67 PWH by using leave-one-out cross-validation. This model generalized to both 33 novel PWH in the testing set and a subset of 39 PWH who completed a follow-up visit two years later. Furthermore, network strengths identified by the CPM model were significantly different between PWH with HAND and without HAND. Together, these results demonstrate that whole-brain functional network strengths could serve as a potential neural biomarker of global cognitive performance in PWH.

Low CD4 nadir linked to widespread cortical thinning in adults living with HIV.

BACKGROUND: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. METHODS: High resolution structural MRI images and neuropsychological data were obtained from fifty-nine HIV+ adults (mean age, 56.5 ± 5.8) to investigate the correlation between CD4 nadir and cortical thickness. RESULTS: Low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions, and global mean cortical thickness correlated with CD4 nadir. In addition, worse global neurocognitive function was associated with bilateral frontal cortical thinning, and the association largely persisted (especially in the left frontal cortex) in the subset of participants who did not meet HAND criteria. CONCLUSIONS: These results suggest that low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. The diffuse neural injury might contribute to the prevalence and the phenotypes of HAND, as well as the difficulty treating HAND due to a broad network of brain regions affected. Low CD4 nadir related neural injury to the frontal cortex might contribute to subtle neurocognitive impairment/decline, even in the absence of HAND diagnosis.

Different roles of frontal versus striatal atrophy in HIV-associated neurocognitive disorders.

Gray matter (GM) atrophy is frequently detected in persons living with HIV, even in the era of combination antiretroviral therapy (cART), but the specificity of regions affected remains elusive. For instance, which regions are consistently affected in HIV? In addition, atrophy at which regions is frequently associated with neurocognitive impairment in HIV? Resolving these questions can potentially help to establish the possible neural profiles of HIV-associated neurocognitive disorders (HAND) severity, which currently is solely defined by neurobehavioral assessments. Here, we addressed these questions using a novel meta-analysis technique, the colocalization-likelihood estimation (CLE) technique, to quantitatively synthesize the findings of GM atrophy in HIV+ adults. Twenty-one of 386 studies published between 1988 and November 2017 and identified in PubMed were selected, plus four identified in other resources. In the end, 25 studies (1,370 HIV+ adults, 889 HIV- controls) were included in the meta-analysis. This technique revealed that GM atrophy in HIV+ adults was dominated by two distinct but nonexclusive profiles: frontal (including anterior cingulate cortex, [ACC]) atrophy, which was associated withHIV-disease and consistently differentiated HIV+ adults from HIV- controls; and caudate/striatum atrophy, which was associated with neurocognitive impairment. The critical role of caudate/striatum atrophy in neurocognitive impairment was further supported by a separate data analysis, which examined the findings of correlation analyses between GM and neurocognitive performance. These results suggest that the frontal lobe and the striatum play critical but differential roles in HAND. A neural model of HAND severity was proposed with several testable predictions.