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Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count.

ABSTRACT: This study investigated structural brain organization using diffusion tensor imaging (DTI) in 35 HIV-positive and 35 HIV-negative individuals. We used global and nodal graph theory metrics to investigate whether HIV was associated with differences in brain network organization based on fractional anisotropy (FA) and mean diffusivity (MD). Participants also completed a comprehensive neuropsychological testing battery. For global network metrics, HIV-positive individuals displayed a lower FA clustering coefficient relative to HIV-negative individuals. For nodal network metrics, HIV-positive individuals had less MD nodal degree in the left thalamus. Within HIV-positive individuals, the FA global clustering coefficient was positively correlated with nadir CD4 cell count. Across the sample, cognitive performance was negatively correlated with characteristic path length and positively correlated with global efficiency for FA. These results suggest that, despite management with combination antiretroviral therapy, HIV infection is associated with altered structural brain network segregation and thalamic centrality and that low nadir CD4 cell count may be a risk factor. These graph theory metrics may serve as neural biomarkers to identify individuals at risk for HIV-related neurological complications.

SUBMITTER: Bell RP

PROVIDER: S-EPMC6105458 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count.

Bell Ryan P RP Barnes Laura L LL Towe Sheri L SL Chen Nan-Kuei NK Song Allen W AW Meade Christina S CS

Journal of neurovirology 20180423 4

This study investigated structural brain organization using diffusion tensor imaging (DTI) in 35 HIV-positive and 35 HIV-negative individuals. We used global and nodal graph theory metrics to investigate whether HIV was associated with differences in brain network organization based on fractional anisotropy (FA) and mean diffusivity (MD). Participants also completed a comprehensive neuropsychological testing battery. For global network metrics, HIV-positive individuals displayed a lower FA clust ...[more]

PMID: 29687404

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Project description:ObjectivesHIV-infected population may have increased risk of cardiovascular disease. The prevalence of traditional cardiovascular disease risk factors such as hypertension, diabetes and dyslipidemia in HIV-infected individuals has made it difficult to assess the direct effects of HIV and immune factors on endothelial dysfunction and associated increased risk of atherosclerosis. The purpose of this study was to investigate indicators of endothelial dysfunction in an HIV cohort without hypertension and diabetes.MethodsWe studied 19 HIV-infected patients between the ages of 25-76?years old with effectively suppressed viral load and without diagnosis of hypertension or diabetes. Endothelial function was measured by digital thermal monitoring of vascular reactivity using the VENDYS technique. Endothelial function was reported as vascular reactivity index. Systolic blood pressure and diastolic blood pressure at the time of VENDYS test were measured and latest lipid panels were recorded. The association between vascular reactivity index and CD4-T cells count, different antiretroviral therapy types (non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, protease inhibitors, integrase inhibitors), vitamins use, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol was investigated.ResultsMean vascular reactivity index was 1.87?±?0.53. Vascular reactivity index, marker of endothelial dysfunction, showed a significant correlation with lower nadir CD4 count (p?=?0.003) as well as low-density lipoprotein cholesterol (p?=?0.02). No additional significant correlation between vascular reactivity index and the rest of the investigated variables was found.ConclusionVascular reactivity index, a clinical predictor of endothelial dysfunction, is associated with lower nadir CD4-T cell and low-density lipoprotein cholesterol in HIV-infected men with no history of hypertension or diabetes and before clinical evidence of cardiovascular disease.

Project description:BackgroundThe contribution of HIV-infection to periodontal disease (PD) is poorly understood. We proposed that immunological markers would be associated with improved clinical measures of PD.MethodsWe performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥ 1 site with periodontal probing depth (PPD) ≥ 5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥ 4.0mm, and bleeding on probing (BOP) at ≥ 4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD.ResultsForty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD.ConclusionDegree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.

Project description:Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20-40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20-35 PMW than during 35-40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage.

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Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count.

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Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count.

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