Topographies of Cortical and Subcortical Volume Loss in HIV and Aging in the cART Era

Abstract

Objectives Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally-biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, and combination antiretroviral therapy (cART), as well as gender and smoking. Design A cross-sectional study of 51 HIV-uninfected (HIV−) and 146 HIV-infected (HIV+) participants. Methods Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (e.g. viral load, CD4, etc.) on brain volumes and NP were investigated using penalized regression (LASSO). Results Two components of interest were visualized using PCA. An aging effect predominated for both components. The first component, a cortically-weighted topography, accounted for a majority of variance across participants (43.5% of variance) and showed independent effects of HIV as well as smoking. A secondary, subcortically-weighted topography (4.6%) showed HIV-status accentuated age-related volume loss. In HIV+ patients, the cortical topography correlated with global NP scores and nadir CD4, while subcortical volume loss was associated with recent viral load. Conclusions Cortical regions showed the most prominent volumetric changes due to aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history while subcortical changes correlated with current immune function. Cognitive function was primarily associated with cortical volume changes. Observed volumetric changes in chronic HIV+ patients may reflect both past infection history and current viral status.

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

“…A previous study conducting similar cross-sectional analysis confers HIV-infection in conjunction with aging is related to cortical volume loss. 48 Our findings of no cross-sectional differences by serostatus alone was unexpected, suggesting the uniqueness of this sample of long-term survivors, although, differences emerged when examining those with HAND compared to controls. Nevertheless, we note progressive atrophy despite minimal baseline cross-sectional findings and can conclude that these changes are not limited to those with past injury.…”

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

“…In particular, CD4 nadir was positively associated with both global cortical area and volume, whereas duration of HIV infection was associated with smaller global cortical volume. Other groups have similarly reported that the severity of the initial immune compromise in HIV has long-term effects on brain area and volume, even when patients are adequately treated ( Guha et al, 2016 ; Hua et al, 2013 ; Sanford et al, 2017 ).…”

HIV-associated neurocognitive disorder

“…Structural MRI often reveals white matter changes of uncertain significance associated with HIV infection, but regional volumetric analysis can be a great tool to investigate progressive degeneration. [52] One of the very promising research imaging tools is PET scanning with ligands binding activated microglia that may be the effector cells for HAND. Early promising reports suggest this technology holds promise for HIV research.…”