CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

neuroimaging features distinguished profiles at P<.01, none reached the P<0.001 threshold. Conclusion: Socio-demographic features, not clinical or neurologic features, distinguished cognitive profiles. Future studies are needed that incorporate additional neuroimaging methods that may be more sensitive to subtle changes in brain integrity that can impact cognition in order to evaluate their importance in distinguishing cognitive profiles.

are widely studied in numerous neurological and psychiatric conditions under a variety of task demands but have not yet been evaluated in virally-suppresesed people with HIV (VS-PWH). Here we examined global brain network organization in virally-suppressed people with HIV under three functional MRI conditions including resting state MRI (rsfMRI) and the performance of verbal memory and go/no-go tasks. Methods: A total of 56 participants (69.6% VS-PWH; 51.7% female, 69.6% black) completed the MRI session and performed a battery of cognitive tests using the iPad-based platform Brain-Baseline Assessment of Cognition and Everyday Functioning. Graph theory metrics of the global functional brain network were computed in the weighted positive network, determined by positive correlations in the BOLD activity, to yield assortativity, characteristic path length (CPL), clustering coefficient (CC), global efficiency (GE), modularity (Q), and average node strength (ANS). Multiple regressions were performed to determine serostatus effects and associations with cognitive performance, adjusting for sex, age, race, ethnicity and education. Results: In resting state, compared to controls, VS-PWH showed lower CC (p=.03), GE (p=.02), and ANS (p=.02) and higher CPL (p=.04) and Q (p=.04). In the verbal memory task, compared to controls, VS-PLWH also showed lower CC (p=.01), GE (p=.02), and ANS (p=.01) and higher CPL (p=.04) and Q (p=.005). No HIV-serostatus effects were observed in the go/no-go task. In the total sample, there were significant associations of CPL, CC, GE, and ANS with processing speed (reaction time on flanker, Stroop, Trail Making, and fine motor skills task), working memory (accuracy on n-back) and visual spatial learning test (total correct across trials). Conclusion: During both the resting state and performance of a verbal memory task, VS-PLWH show less efficiently organized network structure (GE), less small-world network structure (CC, CPL), and less distributed connectivity (Q and ANS). These metrics relate to a number of cognitive processes including processing speed, working memory, and visual spatial learning. Here we show graph theory metrics may serve as biomarker for VS-PLWH to monitor disease progress and to evaluate new therapeutics. HIV Status and APOE4 Differentially Impact White Matter Integrity in Adults With HIV Peyton Thomas 1 , Hannah Walsh 1 , Richard C. Gallagher 1 , Kyle Shattuck 1 , Princy Kumar 1 , David J. Moore 2 , Ronald J. Ellis 3 , Xiong Jiang 1 1 Georgetown University, Washington, DC, USA, 2 University of California San Diego, La Jolla, CA, USA, 3 University of California San Diego, San Diego, CA, USA Background: The median age of people with HIV (PWH) in USA is now over 50. This aging HIV+ population is facing increasingly significant risk of other neurodegenerative diseases-in addition to HIV brain disease-especially Alzheimer's disease. We investigated the potential impact of HIV-disease, APOE4 (E4), and their interactions on white matter (WM) microstructure in a cohort of middle-aged to older PWH. Methods: Seventy-six adults (44-69 y.o. (56.4±6.3), 24 female, 58 PWH) participated in this study. All diffusion weighted images were preprocessed in FSL then analyzed using the automated fiber quantification (AFQ) software in Python. AFQ produced fractional anisotropy (FA) and mean diffusivity (MD) values at each of 100 equidistant nodes along each of 22 major WM bundles. We analyzed group differences along each tract for both FA and MD using pointwise t-tests with FDR correction to investigate the impact of HIV and E4 status on FA and MD values. Significant regions of group differences were defined by pFDR<0.05 with at least two adjacent nodes. Region-of-interest (ROI) based analyses were conducted on these significant regions to investigate the interactions between age, E4, and HIV-disease. Results: Compared to controls, PWH showed trends of increased MD along all 22 bundles, with significant regions of group differences along the left inferior frontal occipital (Fig. A) and left uncinate tracts. ROI-based analyses revealed significant interactions between HIV-status and age in all these regions (at least p<.004), with a steeper age-related increase in MD in PWH. Across PWH and controls, E4 carriers had significantly reduced FA in multiple regions of the left arcuate fasciculus versus non-carriers (Fig. B). In PWH, the E4 effect remained significant (p<.001), and importantly, ROI-based analyses revealed significant interactions between E4 status and HIV disease duration in most of these regions, with a steeper disease duration-related decline in FA in PWH E4 carriers (after controlling for age, ps<.045). Conclusion: HIV and APOE4 differentially impact white matter microstructure in middle-aged to older adults with HIV. Specifically, HIV-disease is associated

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MRI With T2 Maps and Spectroscopy Show Chronic Progressive Brain Damage Despite HIV Suppression David Jakabek 1 , Kurt Lancaster 1 , Lauriane Juge 2 , Caroline D. Rae 2 , Lucette A. Cysique 1 , Bruce J Brew 1 1 St Vincent's Hospital, Sydney, Australia, 2 University of New South Wales, Darlinghurst, Australia Background: We used a 20-minute absolute single-voxel proton magnetic resonance spectroscopy (MRS) scan with relaxometry (T1 and T2 maps) to better quantify water as a reference for major brain metabolites in virally suppressed people living with HIV (PWH) who are aging and were assessed for HIV immune markers and cognitive functions. Methods: 39 PWH, all male (mean age: 53 ± 14, 60+ years old: 35%, HIV duration: 18 years, 20% nadir CD4 <200 cp/mL) were enrolled into a prospective study investigating brain metabolites during long-term viral suppression. They completed a baseline and a two-year follow-up clinical visit for HIV biomarkers (CD4 and CD8 count, nadir CD4, HIV duration), a neuropsychological assessment, a structural brain MRI scan, and a 20-minute single-voxel MRS in the frontal white matter, right caudate, and posterior cingulate with whole brain T1 and T2 mapping to derive the absolute concentration of major brain metabolites. MRS data were fitted with the spant R package and scaled using partial volumes (derived from Freesurfer and FSL MRS tools structural volumes). Mixed effect models assessed associations and longitudinal changes to T1, T2, and metabolite concentrations with age, baseline HIV biomarkers, and HIV associated cognitive disorder (HAND). Results: Higher T2, but not T1 values, increased with age in white and grey matter (p < 0.002). HAND was associated with higher T2 values over time (p < 0.03). Older adults with HAND had higher T2 values than older adults without HAND (p < 0.04). Myo-Inositol concentration increased in all brain regions as a function of increased age (p < 0.01). There was a significant age-by-nadir CD4 interaction in frontal white matter for myo-Inositol (p < 0.001). Lower baseline CD4+ cell count and HAND were associated with lower glutamate in the cingulate (p = 0.04) and caudate (p = 0.003) of older participants, respectively. Conclusion: Our results confirm and expand the evidence for chronic and slowly progressive structural and neurometabolic abnormalities including age related loss of brain tissue density, age and HAND-related inflammation/glial activation, legacy-related (nadir CD4) inflammation/glial activation, but also age, current immune function (baseline CD4) and HAND related excitotoxicity in the cortex and basal ganglia. Our 20-minute absolute concentration MRI/S scan may be clinically scalable to monitor HAND stability or progression in virally suppressed PWH who are aging. Functional Brain Network Changes Among People With HIV and Viral Suppression Jacob Van Doorn 1 , Leah H. Rubin 2 , Farah Naaz 2 , Liuyi Chen 2 , Seble Kassaye 3 , Lakshmi Goparaju 3 , Raha M. Dastgheyb 2 , Asante Kamkwalala 2 , Hannah Lee 2 , Arianna Konstantopoulos 2 , Joan Severson 4 , Olusola Ajilore 1 , Alex Leow 1 , Pauline Maki 1 1 University of Illinois at Chicago, Chicago, IL, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 Georgetown University, Washington, DC, USA, 4 Digital Artefacts, LLC, Iowa City, IA, USA Background: The functional connectivity of global brain networks, quantified using graph theory metrics, provide insights into the efficiency and other characteristics of brain network functioning at a whole brain level. Such metrics

Poster Abstracts

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CROI 2024 161