Subcortical brain atrophy persists even in HAART-regulated HIV disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Becker JT
PROVIDER: S-EPMC3082694 | biostudies-literature | 2011 Jun
REPOSITORIES: biostudies-literature
Publications
Subcortical brain atrophy persists even in HAART-regulated HIV disease.
Becker James T JT Sanders Joanne J Madsen Sarah K SK Ragin Ann A Kingsley Lawrence L Maruca Victoria V Cohen Bruce B Goodkin Karl K Martin Eileen E Miller Eric N EN Sacktor Ned N Alger Jeffery R JR Barker Peter B PB Saharan Priyanka P Carmichael Owen T OT Thompson Paul M PM
Brain imaging and behavior 20110601 2
The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was ...[more]
Similar Datasets
Project description:The purpose of this study was to characterize brain volumetric differences in HIV seropositive and seronegative men and to determine effects of age, cardiovascular risk, and HIV infection on structural integrity.Magnetic resonance imaging was used to acquire high-resolution neuroanatomic data in 160 men aged 50 years and over, including 84 HIV seropositive and 76 seronegative controls. Voxel-based morphometry was used to derive volumetric measurements at the level of the individual voxel. Data from a detailed neuropsychological test battery were recombined into four summary scores representing psychomotor speed, visual memory, verbal memory, and verbal fluency.Both age and HIV status had a significant effect on both gray matter (GM) and white matter (WM) volume. The age-related GM atrophy was primarily in the superior temporal and inferior frontal regions; the HIV-related GM loss included the posterior and inferior temporal lobes, the parietal lobes, and the cerebellum. Among all subjects, the performance on neuropsychological tests, as indexed by a summary variable, was related to the volume of both the GM and WM. Contrary to our predictions, the CVD variables were not linked to brain volume in statistically adjusted models.In the post-HAART era, having HIV infection is still linked to atrophy in both GM and WM. Secondly, advancing age, even in this relatively young cohort, is also linked to changes in GM and WM volume. Thirdly, CNS structural integrity is associated with overall cognitive functions, regardless of the HIV infection status of the study volunteers.
| S-EPMC3154580 | biostudies-literature
Project description:HIV persistence in the brain is a barrier to cure, and potentially contributes to HIV-associated neurocognitive disorders. Whether HIV transcription persists in the brain despite viral suppression with antiretroviral therapy (ART) and is subject to the same blocks to transcription seen in other tissues and blood, is unclear. Here, we quantified the level of HIV transcripts in frontal cortex tissue from virally suppressed or non-virally suppressed people with HIV (PWH). HIV transcriptional profiling of frontal cortex brain tissue (and PBMCs where available) from virally suppressed (n = 11) and non-virally suppressed PWH (n = 13) was performed using digital polymerase chain reaction assays (dPCR). CD68+ myeloid cells or CD3+ T cells expressing HIV p24 protein present in frontal cortex tissue was detected using multiplex immunofluorescence imaging. Frontal cortex brain tissue from PWH had HIV TAR (n = 23/24) and Long-LTR (n = 20/24) transcripts. Completion of HIV transcription was evident in brain tissue from 12/13 non-virally suppressed PWH and from 5/11 virally suppressed PWH, with HIV p24+CD68+ cells detected in these individuals. While a block to proximal elongation was present in frontal cortex tissue from both PWH groups, this block was more extensive in virally suppressed PWH. These findings suggest that the brain is a transcriptionally active HIV reservoir in a subset of virally suppressed PWH.
| S-EPMC11335163 | biostudies-literature
Project description:BackgroundNeurocognitive impairment remains prevalent in HIV-infected (HIV+) individuals despite highly active antiretroviral therapy (HAART). We assessed the impact of HIV, HAART, and aging using structural neuroimaging.MethodsSeventy-eight participants [HIV- (n = 26), HIV+ on stable HAART (HIV+/HAART+; n = 26), HIV+ naive to HAART (HIV+/HAART-; n = 26)] completed neuroimaging and neuropsychological testing. A subset of HIV+ subjects (n = 12) performed longitudinal assessments before and after initiating HAART. Neuropsychological tests evaluated memory, psychomotor speed, and executive function, and a composite neuropsychological score was calculated based on normalized performances (neuropsychological summary Z score, NPZ-4). Volumetrics were evaluated for the amygdala, caudate, thalamus, hippocampus, putamen, corpus callosum, and cerebral gray and white matter. A 3-group 1-way analysis of variance assessed differences in neuroimaging and neuropsychological indices. Correlations were examined between NPZ-4 and volumetrics. Exploratory testing using a broken-stick regression model evaluated self-reported duration of HIV infection on brain structure.ResultsHIV+ individuals had significant reductions in brain volumetrics within select subcortical regions (amygdala, caudate, and corpus callosum) compared with HIV- participants. However, HAART did not affect brain structure as regional volumes were similar for HIV+/HAART- and HIV+/HAART+. No association existed between NPZ-4 and volumetrics. HIV and aging were independently associated with volumetric reductions. Exploratory analyses suggest caudate atrophy due to HIV slowly occurs after self-reported seroconversion.ConclusionsHIV associated volumetric reductions within the amygdala, caudate, and corpus callosum occurs despite HAART. A gradual decline in caudate volume occurs after self-reported seroconversion. HIV and aging independently increase brain vulnerability. Additional longitudinal structural magnetic resonance imaging studies, especially within older HIV+ participants, are required.
| S-EPMC3302928 | biostudies-literature
Project description:BackgroundAcute cerebrovascular accidents, long-term hypoperfusion, and/or remote neuronal degeneration may lead to structural alterations in patients with moyamoya disease (MMD). This study sought to comprehensively investigate the distribution characteristics of subcortical gray matter volume and their correlations with angiographic changes in the intracranial artery in patients with MMD.MethodOne hundred forty-two patients with MMD and 142 age- and sex-matched healthy controls underwent 3-dimensional high-resolution structural magnetic resonance imaging. Volumes of subcortical gray matter and subregions of the hippocampus and amygdala were calculated, and the degree of stenosis/occlusion of intracranial arteries in patients with MMD was evaluated on MR angiography.ResultsVolume reductions in the thalamus, caudate, putamen, hippocampus, amygdala, pallidum, and nucleus accumbens were found in patients with MMD. Hippocampal subfields and amygdala subnuclei in patients with MMD showed distinct vulnerability, and morphological alterations in specific subregions were more obvious than in the whole hippocampus/amygdala. Volume loss in several subcortical areas was related to disease duration and intracranial arterial changes.ConclusionsOur findings revealed structural alteration patterns of subcortical gray matter in MMD. The specific atrophy in subregions of the hippocampus and the amygdala suggested potential cognitive and affective impairments in MMD, which warrants further investigation. Chronic cerebral hemodynamic alterations in MMD may play a pivotal role in morphological changes in subcortical areas.
| S-EPMC10102099 | biostudies-literature
Project description:ObjectiveWe evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs).MethodsIn this cross-sectional study, 35 HIV+ subjects aged ≥40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA <10 copies/10(6) cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV+ subjects were on combination antiretroviral therapy ≥1 year; all but 1 had plasma HIV RNA <50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV+ subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age.ResultsRelative to the HIV+ group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (-14%, p = 0.020) and total subcortical (-10%, p = 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p < 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels.ConclusionInability to clear peripheral blood of HIV DNA is associated with regional brain atrophy in well-controlled HIV infection, supporting the involvement of peripheral viral reservoirs in the neuropathogenesis of persistent HIV-related neurocognitive disorders.
| S-EPMC3719430 | biostudies-literature
Project description:We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients.
2011-03-26 | GSE28177 | GEO
Project description:We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Gut mucosal responses to HAART interruption were evaluated with Affymetrix arrays
2011-03-25 | E-GEOD-28177 | biostudies-arrayexpress
Project description:BackgroundThe effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear.ObjectiveTo determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS.MethodsA non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category.ResultsA total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (-0.15% vs -0.81%; p = 0.001) and putaminal (-0.27% vs -0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume.ConclusionDMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.
| S-EPMC6689465 | biostudies-literature
Project description:BackgroundCognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables.MethodsMultiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry, and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. Ninety percent of the HIV-infected patients were on stable HAART with most of them (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed.ResultsRegionally specific patterns of reduced thalamic and brainstem volumes and reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance.ConclusionsOur findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV and argues for the potential importance of early initiation of HAART to protect long-term brain health.
| S-EPMC5340610 | biostudies-literature
Project description:Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.
| S-EPMC11335513 | biostudies-literature