Our initial project aimed to 1) determine the neural correlates of attentional impairment in HIV-patients with cognitive motor complex (HIV-CMC) using functional MRI (fMRI), and 2) show that fMRI may detect abnormal brain activation in HIV patients with normal neuropsychological function. We have made significant progress despite the relocation and technical delays associated with a scanner upgrade; our work resulted in 8 papers (6 published and 2 in press), 2 manuscripts submitted, and 4 more in preparation (data collection completed and presented at recent meetings, ISMRM and HIV Workshop). We have achieved our two major aims and proven 3 of the 4 original hypotheses. Work from the initial project period provided us with significant experience and strong preliminary data for this new proposal. The new proposal has the following three aims: 1) To evaluate the possible additive or interactive effects of HIV and aging on brain metabolites using longitudinal follow-up proton magnetic resonance spectroscopy (MRS) studies. 2) To evaluate the possible additive or interactive effects of HIV and aging on brain function, especially attention and working memory, as measured by longitudinal blood-oxygenation-level-dependent functional MRI (BOLD-fMRI). 3) To determine the relationships between brain metabolite abnormalities and brain activation in the setting of HIV and aging. These relationships will provide cross-modality validation of the pathophysiological changes associated with HIV and aging. Based on our preliminary data, we hypothesize that compared to younger HIV subjects, less young (>=40 years) HIV individuals will show higher age-related increase in glial markers (choline, myoinositol) and additional decreased neuronal marker N-acetylaspartate on MRS. In addition, less young HIV patients will have more rapid age-related decline in parietal and frontal BOLD activation during attention and working memory tasks on BOLD-fMRI, over the 5-year period. We also hypothesize that the elevated glial markers and total creatine will be related to increased attentional modulation (usage of brain reserve or deactivation of adjacent or same brain regions) on brain activation. To test these hypotheses, we will enroll 75 HIV-patients and 75 seronegative controls (ages 18-80 years, 75% men, and approximately equal distribution across the decades in each group), and follow them annually over a 5-year period. This will enable us to compare the groups both cross-sectionally as well as longitudinally. The knowledge gained from this study will provide a better understanding of how HIV affects the aging brain (even at middle age), and may lead to future preventive measures (e.g. neuroprotective or anti-inflammatory treatments). ? ? ?
| Douet, Vanessa; Tanizaki, Naomi; Franke, Adrian et al. (2016) Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV. J Neuroimmune Pharmacol 11:549-61 |
| Chang, Linda; Jiang, Caroline; Cunningham, Eric et al. (2014) Effects of APOE ?4, age, and HIV on glial metabolites and cognitive deficits. Neurology 82:2213-22 |
| Oishi, Kenichi; Faria, Andreia V; Yoshida, Shoko et al. (2013) Quantitative evaluation of brain development using anatomical MRI and diffusion tensor imaging. Int J Dev Neurosci 31:512-24 |
| Chang, Linda; Holt, John L; Yakupov, Renat et al. (2013) Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging 34:1240-53 |
| Bandaru, Veera Venkata Ratnam; Mielke, Michelle M; Sacktor, Ned et al. (2013) A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects. Neurology 81:1492-9 |
| Chang, Linda; Cloak, Christine C; Jiang, Caroline S et al. (2012) Lower glial metabolite levels in brains of young children with prenatal nicotine exposure. J Neuroimmune Pharmacol 7:243-52 |
| Holt, John L; Kraft-Terry, Stephanie D; Chang, Linda (2012) Neuroimaging studies of the aging HIV-1-infected brain. J Neurovirol 18:291-302 |
| Chang, L; Andres, M; Sadino, J et al. (2011) Impact of apolipoprotein E ýý4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging. Neuroimage 58:1017-27 |
| Andres, Marilou A; Feger, Ute; Nath, Avindra et al. (2011) APOE ? 4 allele and CSF APOE on cognition in HIV-infected subjects. J Neuroimmune Pharmacol 6:389-98 |
| Ernst, Thomas; Yakupov, Renat; Nakama, Helenna et al. (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65:316-25 |
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