SCYLLO-INOSITOL AND OTHER BRAIN METABOLITES IN RELATION TO REGIONAL BRAIN VOLUMES, COGNITION, AND INFLAMMATORY MARKERS IN HIV

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dc.contributor.advisorKallianpur Tata, Kalpana J.
dc.contributor.authorLee, Awapuhi
dc.contributor.departmentBiomed Science (Tropical Medicine)
dc.date.accessioned2021-09-30T18:07:09Z
dc.date.available2021-09-30T18:07:09Z
dc.date.issued2021
dc.description.degreeM.S.
dc.identifier.urihttp://hdl.handle.net/10125/76333
dc.subjectVirology
dc.subjectNeurosciences
dc.titleSCYLLO-INOSITOL AND OTHER BRAIN METABOLITES IN RELATION TO REGIONAL BRAIN VOLUMES, COGNITION, AND INFLAMMATORY MARKERS IN HIV
dc.typeThesis
dcterms.abstractHIV-associated neurocognitive disorders (HAND) are a manifestation of neuropsychological (NP) impairment. Brain atrophy that exceeds normal age-related volumetric loss has been observed in HIV patients with NP impairment, and cerebral metabolites have been associated with reduced regional brain volumes and cognitive impairment. Low levels of scyllo-inositol (sI) were recently found to be related to NP impairment in a cohort of HIV patients with mild-to-moderate cognitive impairment. sI has not been extensively studied in the HIV population, so its role in HIV infection and cognitive impairment is unknown. To elucidate the potential roles of sI and other cerebral metabolites in cognitive impairment, we examined associations between metabolites, regional brain volumes, NP performance, and inflammatory markers in HIV+ individuals on combination antiretroviral therapy (cART) who had mild-to-moderate cognitive impairment. We also examined changes in metabolites among HIV patients before and after initiation of Cenicriviroc (CVC) or Maraviroc (MVC).Magnetic resonance imaging (MRI) was used to obtain T1-weighted scans, which were processed using FreeSurfer (version 6.0) to obtain regional brain volumes and total intracranial volume (ICV) of HIV+ participants (N=30) from the CVC and Maraviroc MVC studies from the Hawaiʻi Center for AIDS. Single-voxel magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopy imaging (MRSI) at 3T was used to measure brain metabolites. Participants underwent NP tests in multiple domains. Immune and inflammatory markers were measured by multi-parametric flow cytometry. Multivariable regression models, Pearson and Spearman correlations, Wilcoxon signed-ranked tests, and Mann-Whitney tests were performed using SPSS (versions 26 and 27). There were many significant associations and correlations between cerebral metabolites, regional brain volumes, NP domains, and inflammatory markers. Choline concentrations increased among patients treated with CVC. HIV patients in the MVC treatment group vs. the placebo group had higher mean differences in GABA and choline. Our study identified multiple associations between cerebral metabolites and regional brain volumes, including sI being positively associated with the putamen, cerebellar cortex and white matter, and the brain stem. This metabolite should be studied further as it could play a role in improving brain health and neurocognitive performance among HIV+ individuals.
dcterms.extent94 pages
dcterms.languageen
dcterms.publisherUniversity of Hawai'i at Manoa
dcterms.rightsAll UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dcterms.typeText
local.identifier.alturihttp://dissertations.umi.com/hawii:11110

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