HIV and age underlie specific patterns of brain abnormalities and cognitive changes in high functioning patients.

OBJECTIVE: Findings on the influence of age and HIV on brain and cognition remain equivocal, particularly in aviremic subjects without other age or HIV-related comorbidities. We aimed to (a) examine the effect of HIV status and age on structural brain measurements and cognition, and (b) apply the machine learning technique to identify brain morphometric and cognitive features that are most discriminative between aviremic subjects with HIV on stable combination antiretroviral therapy (cART) and healthy controls. METHOD: Fifty-three HIV-seropositive patients and 62 healthy controls underwent neuropsychological testing (executive functions, attention, memory, learning, psychomotor speed, fluency) and volumetric MRI scans. Voxel-based morphometry, ANCOVAs, machine learning, and multivariate regression were conducted to determine the between group differences in terms of relationship of HIV status, age, and their interaction on neurocognitive and structural brain measures. RESULTS: Volume and gray matter (GM) thickness of the caudate, parahippocampus, insula, and inferior frontal gyrus were smaller in seropositive subjects in comparison with healthy controls (HC). They also performed worse in complex attention and cognitive fluency tasks. Support vector machine (SVM) analysis revealed that the best between-groups classification accuracy was obtained based on cognitive scores encompassing complex attention and psychomotor speed, as well as volumetric measures of white matter and total gray matter; third, fourth, and lateral ventricles; amygdala; caudate; and putamen. Both voxel-based morphometry (VBM) and regression analysis yielded that HIV and aging independently increase brain vulnerability and cognitive worsening. CONCLUSION: Patients with HIV on effective cART demonstrate smaller volumetric measures and worse cognitive functioning relative to seronegative individuals. There is no interaction between HIV infection and aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

HIV infection across aging: Synergistic effects on intrinsic functional connectivity of the brain.

The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV-) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20-55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients.

Age and HIV effects on resting state of the brain in relationship to neurocognitive functioning.

This study examined the effects of age and HIV infection on the resting state (RS) functional connectivity (FC) of the brain and cognitive functioning. The objective was to evaluate the moderating role of age and HIV on the relationship between RS-FC and cognition. To examine RS-FC we implemented the Independent Component Analysis (ICA) and Regional Homogeneity (ReHo). Neurocognition was evaluated with comprehensive battery of standardized neuropsychological tests. Age and HIV were entered as the independent variables. The independent effects of age, HIV, and interaction effects of age-HIV on RS-fMRI measures (ICA, ReHo) were tested in 108 participants (age M = 42). RS-FC indices that exhibited age-HIV interactions were entered into further analysis. Bivariate correlation analysis was performed between the retained RS-FC indices and T-scores of neurocognitive domains (Attention, Executive, Memory, Psychomotor, Semantic Skills). Multivariate regression modeling determined the impact of age and HIV on these relationships. We found that in the ICA measures, HIV-seropositivity was decreasing RS-FC in the left middle occipital gyrus (p < .001). Age-HIV interaction was observed in the left superior frontal gyrus (LSupFrontG), where FC was decreasing with age in HIV+ (p < .001) and increasing in HIV- (p = .031). ReHo indices did not reveal significant effects. HIV strengthened the relationship between RS-FC in LSupFrontG, Memory and Psychomotor Factor scores. Aging weakened those relationships only in control group. In sum, age-HIV interaction effects are prominent rather in remote than local RS-FC. Seroconversion strengthens relationships between intrinsic brain activity and neurocognition, but no acceleration with years of age was noted in HIV+ individuals.