Regional Cerebral Gray Matter Volume in HIV‐Positive Patients with Executive Function Deficits

Corrêa, Diogo Goulart; Zimmermann, Nicolle; Netto, Tania Maria; Tukamoto, Gustavo; Ventura, Nina; Leite, Sarah de Castro Bellini; Cabral, Rafael Ferracini; Fonseca, Róchele Paz; Bahia, Paulo Roberto Valle; Gasparetto, Emerson L.

doi:10.1111/jon.12327

Cited by 31 publications

(14 citation statements)

References 29 publications

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“…In some studies, HIV infection has been associated with reduced cortical volume ( Stout et al, 1998 ; Behrman-Lay et al, 2016 ) or with regional cortical thinning ( du Plessis et al, 2016 ; Shin et al, 2017 ; Sanford et al, 2018b ; Sanford et al, 2017 ; Thompson et al, 2005 ). Other studies have found no difference in either cortical volume or thickness associated with HIV infection ( Cole et al, 2018 ; Sanford et al, 2018a ; Corrêa et al, 2016a ; Seilhean et al, 1993 ). A recent meta-analysis found that total gray matter volume was significantly smaller among HIV infected individuals than among non-infected controls, although the standardized mean difference was small (−0.28; O'Connor et al, 2018 ).…”

Section: Introductionmentioning

confidence: 74%

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

MacDuffie

Brown

McKenna

et al. 2018

NeuroImage: Clinical

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ObjectiveThis study examined the effects of HIV infection, methamphetamine dependence and their interaction on cortical thickness, area and volume, as well as the potential interactive effects on cortical morphometry of HIV and methamphetamine with age.MethodT1-weighted structural images were obtained on a 3.0T General Electric MR750 scanner. Freesurfer v5.3.0 was used to derive cortical thickness, area and volume measures in thirty-four regions based on Desikan-Killiany atlas labels.ResultsFollowing correction for multiple statistical tests, HIV diagnosis was not significantly related to cortical thickness or area in any ROI, although smaller global cortical area and volume were seen in those with lower nadir CD4 count. HIV diagnosis, nevertheless, was associated with smaller mean cortical volumes in rostral middle frontal gyrus and in the inferior and superior parietal lobes. Methamphetamine dependence was significantly associated with thinner cortex especially in posterior cingulate gyrus, but was not associated with cortical area or volume following correction for multiple statistical tests. We found little evidence that methamphetamine dependence moderated differences in cortical area, volume or thickness for any ROI in the HIV seropositive group. Interactions with age revealed that HIV diagnosis attenuated the degree of age-related cortical thinning seen in non-infected individuals; intercepts indicated that young HIV seropositive individuals had thinner cortex than non-infected peers.ConclusionsMethamphetamine dependence does not appear to potentiate a reduction of cortical area, volume or thickness in HIV seropositive individuals. The finding of thinner cortex in young HIV seropositive individuals and the association between CD4 nadir and global cortical area and volume argue for prioritizing early antiretroviral treatment.

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Section: Introductionmentioning

confidence: 74%

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

MacDuffie

Brown

McKenna

et al. 2018

NeuroImage: Clinical

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“…However, given the high prevalence of tobacco use amongst HIV+ patients,(Tesoriero et al, 2010) those in the earlier studies might have been tobacco smokers also. Earlier studies of HIV+ participants found poorer performance on WCST only in those with AIDS compared to the SN controls (Villa et al, 1993), or in those with smaller striatal structures, especially caudate and putamen (Correa et al, 2016), although information regarding the smoking status of these participants were not reported. Since the caudate and putamen have the highest densities of dopaminergic synapses and reciprocal projections to the orbitofrontal brain regions, deficits in dopaminergic system would lead to impairments in the frontostriatal or prefrontal networks, which may lead to poorer inhibitory control, attention/working memory and decision-making (Braver and Cohen, 2000).…”

Section: Discussionmentioning

confidence: 91%

Chronic Tobacco-Smoking on Psychopathological Symptoms, Impulsivity and Cognitive Deficits in HIV-Infected Individuals

Chang

Lim

Lau

et al. 2017

J Neuroimmune Pharmacol

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HIV-infected individuals (HIV+) has 2–3 times the rate of tobacco smoking than the general population, and whether smoking may lead to greater psychiatric symptoms or cognitive deficits remains unclear. We evaluated the independent and combined effects of being HIV+ and chronic tobacco-smoking on impulsivity, psychopathological symptoms and cognition. 104 participants [27 seronegative (SN)-non-Smokers, 26 SN-Smokers, 29 HIV+non-Smokers, 22 HIV+Smokers] were assessed for psychopathology symptoms (Symptom Checklist-90, SCL-90), depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), impulsivity (Barratt Impulsiveness Scale, BIS), decision-making (The Iowa Gambling Task, IGT, and Wisconsin Card Sorting Test, WCST), and cognition (seven neurocognitive domains). Both HIV+ and Smoker groups had higher SCL-90 and CES-D scores, with highest scores in HIV+Smokers. On BIS, both HIV+ and Smokers had higher Total Impulsiveness scores, with higher behavioral impulsivity in Smokers, highest in HIV+Smokers. Furthermore, across the four groups, HIV+Smokers lost most money and made fewest advantageous choices on the IGT, and had highest percent errors on WCST. Lastly, HIV+ had lower z-scores on all cognitive domains, with the lowest scores in HIV+Smokers. These findings suggest that HIV-infection and chronic tobacco smoking may lead to additive deleterious effects on impulsivity, psychopathological (especially depressive) symptoms and cognitive dysfunction. Although greater impulsivity may be premorbid in HIV+ and Smokers, the lack of benefits of nicotine in chronic Smokers on attention and psychopathology, especially those with HIV-infection, may be due to the negative effects of chronic smoking on dopaminergic and cardio-neurovascular systems. Tobacco smoking may contribute to psychopathology and neurocognitive disorders in HIV+ individuals.

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“…We speculate that our data reflect the particular vulnerability of the PCC to HIV-induced neuroinflammation, which could have consequences for neurocognitive functioning. The prevalence of deficits in executive functioning is high in PLWH, even in those not meeting the full diagnostic criteria for HIV-NCI (Correa et al 2016). Indeed, functional neuroimaging studies have identified metabolic abnormalities in the PCC that associate with HIV infection and with progression of HIV-NCI, as well as abnormal aging and amyloid pathology in the HIV-negative population (Bladowska et al 2013;Cysique et al 2018;Murray et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Cysique et al (2018Cysique et al ( , 2013 used magnetic resonance spectroscopy to detect neuronal injury (reduced N-acetyl-aspartate (NAA)) and neuroinflammation (increased myoinositol (mI)) in PCC in virally suppressed PLWH compared to HIV-negative individuals. However, we cannot attribute deficits in executive function solely to involvement of the PCC in our PLWH cohort, as such dysfunction is also affected by other brain regions, including frontal cortex and white matter, precuneus, accumbens, putamen, and globus pallidus (Correa et al 2016;Mohamed et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

et al. 2020

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Previous studies showed that persons living with HIV (PLWH) demonstrate higher brain prefrontal cortex neuroinflammation and immunoproteasome expression compared to HIV-negative individuals; these associate positively with HIV levels. Lower expression of the antioxidant enzyme heme oxygenase 1 (HO-1) was observed in PLWH with HIV-associated neurocognitive impairment (HIV-NCI) compared to neurocognitively normal PLWH. We hypothesized that similar expression patterns occur throughout cortical, subcortical, and brainstem regions in PLWH, and that neuroinflammation and immunoproteasome expression associate with lower expression of neuronal markers. We analyzed autopsied brains (15 regions) from 9 PLWH without HIV-NCI and 7 matched HIV-negative individuals. Using Western blot and RT-qPCR, we quantified synaptic, inflammatory, immunoproteasome, endothelial, and antioxidant biomarkers, including HO-1 and its isoform heme oxygenase 2 (HO-2). In these PLWH without HIV-NCI, we observed higher expression of neuroinflammatory, endothelial, and immunoproteasome markers in multiple cortical and subcortical regions compared to HIV-negative individuals, suggesting a global brain inflammatory response to HIV. Several regions, including posterior cingulate cortex, globus pallidus, and cerebellum, showed a distinct pattern of higher type I interferon (IFN)-stimulated gene and immunoproteasome expression. PLWH without HIV-NCI also had (i) stable or higher HO-1 expression and positive associations between (ii) HO-1 and HIV levels (CSF, plasma) and (iii) HO-1 expression and neuroinflammation, in multiple cortical, subcortical, and brainstem regions. We observed no differences in synaptic marker expression, suggesting little, if any, associated neuronal injury. We speculate that this may reflect a neuroprotective effect of a concurrent HO-1 antioxidant response despite global neuroinflammation, which will require further investigation.

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Regional Cerebral Gray Matter Volume in HIV‐Positive Patients with Executive Function Deficits

Abstract: HIV-positive patients with executive functions deficits have reduced volumes of several subcortical structures, primarily in the caudate nucleus.

Cited by 31 publications

References 29 publications

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

Chronic Tobacco-Smoking on Psychopathological Symptoms, Impulsivity and Cognitive Deficits in HIV-Infected Individuals

Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

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