Poster No:
319
Submission Type:
Abstract Submission
Authors:
Richard Gallagher1, Kyle Shattuck2, David Moore3, Ronald Ellis3, Xiong Jiang4
Institutions:
1Georgetown University, Charlottesville, VA, 2Georgetown University, Washington, DC, 3UCSD, San Diego, CA, 4Georgetown University Medical Center, Washington, DC
First Author:
Co-Author(s):
Xiong Jiang
Georgetown University Medical Center
Washington, DC
Introduction:
People living with HIV (PLWH), despite having achieved viral suppression via combination antiretroviral therapy, remain at greater risk than uninfected peers for developing global cognitive deficits. Here we conducted a cross-sectional investigation of neuromorphometric changes linked to HIV-disease and HIV-associated neurocognitive disorders (HAND), respectively.
Methods:
High-resolution (1mm-isometric) T1-weighted rapid-acquisition gradient echo images were acquired from 104 PLWH (40-70 years old (mean age = 56.2), 26% female at birth, 64% Black) and 46 demographically matched uninfected controls (mean age = 57.3, 33% female at birth, 52% Black) using a 3.0 Tesla Siemens Magnetom Trio scanner equipped with a 12-channel head coil (n = 88) or a 3.0 Tesla Siemens Prisma-Fit scanner and 20-channel coil (n = 62). Participants were administered a comprehensive set of neuropsychological tests for HAND diagnosis using Frascati criteria. In addition to reporting historical CD4+ T-lymphocyte counts, a proxy for disease severity, PLWH provided blood specimens to confirm viral suppression. MR data were preprocessed using fMRIPrep 20.2.6, and whole-brain voxel based morphometry analysis was performed using the CAT12 toolbox in SPM. Additional vertex-wise estimates of gray matter volume (GMv) and cortical thickness (CT) were determined via surface-based analyses in FreeSurfer v6.0. Subsequent region-of-interest (ROI) analyses were performed using general linear models in R/RStudio.
Results:
Following probabilistic threshold-free cluster enhancement, whole-brain voxelwise analyses revealed significant clusters of cortical atrophy among PLWH in temporal (pFWE-corr < .001, k = 397) and right cerebellar (pFWE-corr < .001, k = 720) cortex, relative to uninfected controls. Surface-based and ROI analyses revealed additional evidence for atrophy in PLWH, relative to controls, irrespective of global cognitive impairment: At p<.01, lower CD4+ T lymphocyte nadir corresponded to lower GMv and CT in left caudal ACC and right temporal pole among patients, and global cognitive impairment among PLWH was strongly associated with decreased white matter volume in a right cerebellar ROI (p<.001). Notably, the inclusion/removal of a covariate to account for scanner type in the above models did not impact study conclusions.
Conclusions:
Despite the heterogeneous nature of the studied population, there is mounting evidence for a distinguishable neuromorphometric profile linking chronic infection to cognitive decline. These findings have implications for the establishment of a noninvasive biomarker for HAND among PLWH, which could serve to identify patients at greater risk of impairment. Historically, very few studies have considered the role of cerebellum in HAND, whereas the current study demonstrated a significant association between global cognitive impairment and altered cerebellar morphometry among virally-suppressed PLWH. Future studies should further investigate the observed relationship between cerebellar atrophy and HAND diagnosis.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Higher Cognitive Functions:
Higher Cognitive Functions Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Neuroanatomy Other 2
Keywords:
Morphometrics
MRI
STRUCTURAL MRI
Other - HIV
1|2Indicates the priority used for review
Provide references using author date format
Antinori A, et al. (2007), 'Updated research nosology for HIV-associated neurocognitive disorders', Neurology, vol 69:1789–1799.
Heaton RK, et al. 92010), 'HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study', Neurology, 75:2087–2096.
Israel SM et al. (2019), 'Different roles of frontal versus striatal atrophy in HIV-associated neurocognitive disorders', Hum Brain Mapp, 40(10):3010-3026.