Regional patterns of brain metabolites in AIDS dementia complex

Yiannoutsos, Constantin T.; Ernst, Thomas; Chang, Linda; Lee, P. Lani; Richards, Todd; Marra, Christina M.; Meyerhoff, Dieter J.; Jarvik, Jeffrey G.; Kolson, Dennis L.; Schifitto, Giovanni; Ellis, Ronald J.; Swindells, Susan; Simpson, David M.; Miller, Eric N.; González, R. Gilberto; Navia, Bradford

doi:10.1016/j.neuroimage.2004.07.033

Cited by 84 publications

(77 citation statements)

References 39 publications

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“…Cerebral MI levels have been linked to HIV status and history in past studies (Chang et al, 1999(Chang et al, , 2002Yiannoutsos et al, 2004;Sacktor et al, 2005;Tarasow et al, 2003). There is evidence that MI levels are associated with gliosis and inflammatory response Jones et al, 2004;Broom et al, 2007;Tkac et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Glx abnormalities have also been observed among patients with HIV, though the neuropathological implications are unclear. Furthermore, there is mounting evidence that cerebral metabolite abnormalities detected on MRS are associated with impaired neurocognitive function and that they are greatest among people with HIV-associated dementia Paul et al, 2007Paul et al, , 2008Patel et al, 2003;Yiannoutsos et al, 2004). Yet, the relationship of these cerebral metabolites to structural brain abnormalities in HIV has not been well delineated, and a full understanding of the evolution of cortical and subcortical injury in the context of chronic infection is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Cohen

Harezlak

Gongvatana

et al. 2010

Journal of NeuroVirology

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Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Cohen

Harezlak

Gongvatana

et al. 2010

Journal of NeuroVirology

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“…Brain regions such as the hippocampus, basal ganglia, and forebrain, which are susceptible to NMDAR-mediated excitotoxicity, are particularly vulnerable in HIV infection as well (Masliah et al, 1992;Petito et al, 2001;Archibald et al, 2004;Sa et al, 2004), and in vitro neuronal death caused by HIV/MDM can be effectively blocked by NMDA receptor (NMDAR) antagonists (Giulian et al, 1990;Lipton, 1993;Kaul et al, 2001). These observations suggest a role for NMDARs in the neurodegeneration induced by HIV-1 infection, and they have prompted clinical HIV neuroprotection trials with NMDAR antagonists (Lipton, 2004;Yiannoutsos et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Human Immunodeficiency Virus (HIV)-Induced Neurotoxicity: Roles for the NMDA Receptor Subtypes

O’Donnell¹,

Agrawal²,

Jordan‐Sciutto³

et al. 2006

J. Neurosci.

148

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“…These studies have included structural and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and other imaging techniques. Some of the earliest neuroimaging studies of HAND utilized MRS and found widespread evidence of aberrant metabolite levels suggesting severe inflammation and neural loss at all stages of infection [7]–[11]. Several fMRI studies have investigated neural activation during attention and working memory tasks in HIV-infected patients with and without cognitive impairment [12]–[16].…”

Section: Introductionmentioning

confidence: 99%

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

et al. 2013

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ObjectiveShortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.MethodsHigh-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.ResultsUninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.ConclusionsMEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

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Regional patterns of brain metabolites in AIDS dementia complex

Cited by 84 publications

References 39 publications

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

Human Immunodeficiency Virus (HIV)-Induced Neurotoxicity: Roles for the NMDA Receptor Subtypes

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

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