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HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study

BACKGROUND: Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. METH...

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Autores principales: Cysique, Lucette A., Moffat, Kirsten, Moore, Danielle M., Lane, Tammy A., Davies, Nicholas W. S., Carr, Andrew, Brew, Bruce J., Rae, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631163/
https://www.ncbi.nlm.nih.gov/pubmed/23620788
http://dx.doi.org/10.1371/journal.pone.0061738
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author Cysique, Lucette A.
Moffat, Kirsten
Moore, Danielle M.
Lane, Tammy A.
Davies, Nicholas W. S.
Carr, Andrew
Brew, Bruce J.
Rae, Caroline
author_facet Cysique, Lucette A.
Moffat, Kirsten
Moore, Danielle M.
Lane, Tammy A.
Davies, Nicholas W. S.
Carr, Andrew
Brew, Bruce J.
Rae, Caroline
author_sort Cysique, Lucette A.
collection PubMed
description BACKGROUND: Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. METHODS: 92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent (1)H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. RESULTS: Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p = .01); and in the posterior cingulate cortex: higher mIo (p<.008– also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. CONCLUSIONS: In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation.
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spelling pubmed-36311632013-04-25 HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study Cysique, Lucette A. Moffat, Kirsten Moore, Danielle M. Lane, Tammy A. Davies, Nicholas W. S. Carr, Andrew Brew, Bruce J. Rae, Caroline PLoS One Research Article BACKGROUND: Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. METHODS: 92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent (1)H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. RESULTS: Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p = .01); and in the posterior cingulate cortex: higher mIo (p<.008– also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. CONCLUSIONS: In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation. Public Library of Science 2013-04-19 /pmc/articles/PMC3631163/ /pubmed/23620788 http://dx.doi.org/10.1371/journal.pone.0061738 Text en © 2013 Cysique et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cysique, Lucette A.
Moffat, Kirsten
Moore, Danielle M.
Lane, Tammy A.
Davies, Nicholas W. S.
Carr, Andrew
Brew, Bruce J.
Rae, Caroline
HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title_full HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title_fullStr HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title_full_unstemmed HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title_short HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A (1)H MRS Study
title_sort hiv, vascular and aging injuries in the brain of clinically stable hiv-infected adults: a (1)h mrs study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631163/
https://www.ncbi.nlm.nih.gov/pubmed/23620788
http://dx.doi.org/10.1371/journal.pone.0061738
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