Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease.
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ABSTRACT:
SUBMITTER: Popov M
PROVIDER: S-EPMC6616021 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo assess the structural correlates of cognitive and behavioral impairment in motor neuron diseases (MND) using multimodal MRI.MethodsOne hundred one patients with sporadic MND (56 classic amyotrophic lateral sclerosis, 31 upper motor neuron phenotype, and 14 lower motor neuron phenotype) and 51 controls were enrolled. Patients were classified into MND with a pure motor syndrome (MND-motor) and with cognitive/behavioral symptoms (MND-plus). Cortical thickness measures and diffusion tensor (DT) metrics of white matter (WM) tracts were assessed. A random forest approach was used to explore the independent role of cortical and WM abnormalities in explaining major cognitive and behavioral symptoms.ResultsThere were 48 MND-motor and 53 MND-plus patients. Relative to controls, both patient groups showed a distributed cortical thinning of the bilateral precentral gyrus, insular and cingulate cortices, and frontotemporal regions. In all regions, there was a trend toward a more severe involvement in MND-plus cases, particularly in the temporal lobes. Both patient groups showed damage to the motor callosal fibers, which was more severe in MND-plus. MND-plus patients also showed a more severe involvement of the extra-motor WM tracts. The best predictors of executive and non-executive deficits and behavioral symptoms in MND were diffusivity abnormalities of the corpus callosum and frontotemporal tracts, including the uncinate, cingulum, and superior longitudinal fasciculi.ConclusionsCortical thinning and WM degeneration are highly associated with neuropsychological and behavioral symptoms in patients with MND. DT MRI metrics seem to be the most sensitive markers of extra-motor deficits within the MND spectrum.
| S-EPMC6867462 | biostudies-literature
Project description:Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection and the best prognostic indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) restores normal immune response and effectively prolongs life. In HIV-infected individuals who are coinfected with hepatitis C virus (HCV) the immune system is activated despite effective HIV antiretroviral therapy controlling viral load. Here we examined CD14+ monocyte gene expression by high-density microarray analysis and T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV, monoinfected HIV and HIV/HCV coinfected subjects with undetected HIV viral load. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological (NP) performance, which was summarized as global deficit scores (GDS). Gene expression analysis of CD14+ monocytes from coinfected subjects revealed an elevated type 1 interferon (IFN) response profile unique to coinfection. For both CD4 and CD8 T cells, coinfection triggered significantly increased expression of activation markers CD38 and HLA-DR. In the coinfected group, mild cognitive impairment was associated with a type 1 IFN monocyte response but not plasma lipopolysaccharide. These observations raise the possibility that cognitive impairment evident in the HIV/HCV population is associated with the IFN response detected in coinfected individuals. Monocytes isolated from healthy controls (n=17), HCV monoinfected (n=19) and HIV/HCV coinfected (n=17) were analyzed for gene expression using high-density microarrays. Whole blood was collected in Vacutainer CPT tubes (BD Biosciences) and PBMCs were enriched by centrifugation. Typically, three million CD14+ monocytes were isolated from 30 ml of whole blood using an anti-CD14 monoclonal antibody immunomagnetic - ferrous bead conjugate according to the manufacturer’s instructions (Miltenyi Biotech). Monocyte purity exceeded 97% with <1% T or B cell contamination as determined by flow cytometry. Monocyte RNA was isolated using a Qiagen RNeasy Micro Kit with an RNA integrity value exceeding 9. Complementary DNA was synthesized and labeled with biotin (iExpress iAmplify kit, Applied Microarrays) and hybridized to Codelink Whole Human Genome Bioarrays (55K probes, Applied Microarrays). Slides were scanned (Axon GenePix 4000B, Molecular Devices), analyzed (CodeLink Expression Software Kit v4.1) and microarray data were normalized with loess normalization using R and Bioconductor package. Determination of differential gene expression and multiple testing correction / false discovery rate adjustments were performed using GeneSpring GX 7.3 software package (Agilent). Microarray data was analyzed using a variety of custom data analytic techniques for gene expression profile identification as described previously. Correlations were determined by Spearman rank correlation coefficient.
2012-06-06 | E-GEOD-38542 | biostudies-arrayexpress
Project description:Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain.Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task.No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls.Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.
| S-EPMC4957815 | biostudies-literature
Project description:Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.
| S-EPMC4474362 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging (structural magnetic resonance imaging (MRI), diffusion MRI, and functional MRI) and neurophysiological techniques (electroencephalography and magnetoencephalography) with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment (MCI), the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks (i.e., connectomics) and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.
| S-EPMC5562665 | biostudies-other
Project description:BackgroundA minimally invasive blood-based assessment of cognitive function could be a promising screening strategy to identify high-risk groups for the incidence of Alzheimer's disease.MethodsThe study included 448 cognitively unimpaired men (mean age 64.1 years) drawn from the Geelong Osteoporosis Study. A targeted mass spectrometry-based proteomic assay was performed to measure the abundance levels of 269 plasma proteins followed by linear regression analyses adjusted for age and APOE ε4 carrier status to identify the biomarkers related to overall cognitive function. Furthermore, two-way interactions were conducted to see whether Alzheimer's disease-linked genetic variants or health conditions modify the association between biomarkers and cognitive function.ResultsTen plasma proteins showed an association with overall cognitive function. This association was modified by allelic variants in genes ABCA7, CLU, BDNF and MS4A6A that have been previously linked to Alzheimer's disease. Modifiable health conditions such as mood disorders and poor bone health, which are postulated to be risk factors for Alzheimer's disease, also impacted the relationship observed between protein marker levels and cognition. In addition to the univariate analyses, an 11-feature multianalyte model was created using the least absolute shrinkage and selection operator regression that identified 10 protein features and age associated with cognitive function.ConclusionsOverall, the present study revealed plasma protein candidates that may contribute to the development of a blood-based screening test for identifying early cognitive changes. This study also highlights the importance of considering other risk factors in elucidating the relationship between biomarkers and cognition, an area that remains largely unexplored.
| S-EPMC10472730 | biostudies-literature
Project description:Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.
| S-EPMC3578833 | biostudies-literature
Project description:Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection and the best prognostic indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) restores normal immune response and effectively prolongs life. In HIV-infected individuals who are coinfected with hepatitis C virus (HCV) the immune system is activated despite effective HIV antiretroviral therapy controlling viral load. Here we examined CD14+ monocyte gene expression by high-density microarray analysis and T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV, monoinfected HIV and HIV/HCV coinfected subjects with undetected HIV viral load. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological (NP) performance, which was summarized as global deficit scores (GDS). Gene expression analysis of CD14+ monocytes from coinfected subjects revealed an elevated type 1 interferon (IFN) response profile unique to coinfection. For both CD4 and CD8 T cells, coinfection triggered significantly increased expression of activation markers CD38 and HLA-DR. In the coinfected group, mild cognitive impairment was associated with a type 1 IFN monocyte response but not plasma lipopolysaccharide. These observations raise the possibility that cognitive impairment evident in the HIV/HCV population is associated with the IFN response detected in coinfected individuals.
2012-06-07 | GSE38542 | GEO
Project description:BackgroundStructural network alterations in Alzheimer's disease (AD) are related to worse cognitive impairment. The aim of this study was to quantify the alterations in gray matter associated with impaired cognition and their pathological biomarkers in AD-spectrum patients.MethodsWe extracted gray matter networks from 3D-T1 magnetic resonance imaging scans, and a graph theory analysis was used to explore alterations in the network metrics in 34 healthy controls, 70 mild cognitive impairment (MCI) patients, and 40 AD patients. Spearman correlation analysis was computed to investigate the relationships among network properties, neuropsychological performance, and cerebrospinal fluid pathological biomarkers (i.e., Aβ, t-tau, and p-tau) in these subjects.ResultsAD-spectrum individuals demonstrated higher nodal properties and edge properties associated with impaired memory function, and lower amyloid-β or higher tau levels than the controls. Furthermore, these compensations at the brain regional level in AD-spectrum patients were mainly in the medial temporal lobe; however, the compensation at the whole-brain network level gradually extended from the frontal lobe to become widely distributed throughout the cortex with the progression of AD.ConclusionThe findings provide insight into the alterations in the gray matter network related to impaired cognition and pathological biomarkers in the progression of AD. The possibility of compensation was detected in the structural networks in AD-spectrum patients; the compensatory patterns at regional and whole-brain levels were different and the clinical significance was highlighted.
| S-EPMC7947929 | biostudies-literature
Project description:Background and purposeMMD has been shown to result in impairment of executive functioning in adults. The purpose of this study was to correlate presurgical neuropsychological assessments with the severity of primary MMD as measured by CBF and CVR and with secondary damage from MMD as estimated by cortical stroke and WMD.Materials and methodsA retrospective analysis of 31 adult patients with MMD was performed. Xe-CT was used to obtain CBF and CVR, and MRI was reviewed to grade cortical stroke and WMD. Two tests of executive functioning (FAS and TMT-B) were correlated with imaging findings. A multiple regression analysis was performed.ResultsThere was a significant overall positive relationship between mean CBF and FAS (P = .038) and TMT-B scores (P = .014). A significant negative relationship was present between the WMD score and the FAS (P = .009) and TMT-B scores (P = .015). Per-region analysis demonstrated that FAS and TMT-B scores were significantly decreased by the presence of a posterior stroke (P < .0001 and P = .001) or WMD (P = .006 and P = .004). All patients with posterior parieto-occipital WMD or stroke also had secondary disease in the anterior regions.ConclusionsImpaired executive functioning in adults with MMD is most strongly associated secondary damage in the form of WMD or cortical stroke. The effect is most profound with parieto-occipital lobe involvement, likely a reflection of overall disease severity. Increasing global WMD burden may be a better indicator of cognitive decline than cortical infarction. Patients with higher baseline CBF seem to have better cognitive functioning.
| S-EPMC8050434 | biostudies-literature