Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Abstract

Background: Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables.

Methods: Multiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry, and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. Ninety percent of the HIV-infected patients were on stable HAART with most of them (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed.

Results: Regionally specific patterns of reduced thalamic and brainstem volumes and reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance.

Conclusions: Our findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV and argues for the potential importance of early initiation of HAART to protect long-term brain health.

Figure 1

Reductions in cortical thickness in HIV-infected patients were associated with worse neuropsychological performance (as indexed by Rasch scoring) in the left lateral temporal pole, left inferior occipital, right lateral occipital, and right inferior lateral frontal cortices. (Image created with SurfStat http://www.math.mcgill.ca/keith/surfstat/).

Figure 2

Axial slices of voxel-based morphometry (VBM) differences in HIV-infected compared to HIV-uninfected subjects. Reductions in WM were detected in the brainstem and thalamus. (Image created with MRIcron http://people.cas.sc.edu/rorden/mricron/index.html)

Figure 3

Cortical modeling showed significant cortical thickness reductions in HIV-infected patients compared to HIV-uninfected participants specifically within the right primary motor and sensory cortex, lateral temporal and frontal lobes, and posterior cingulate, orbitofrontal cortex and left anterior cingulate. (Image created with SurfStat http://www.math.mcgill.ca/keith/surfstat/).

Figure 4

A) Axial slices of voxel-based morphometry (VBM) results show significant WM reductions in the brainstem, globus pallidus, internal capsule, caudate, and right frontal lobe that were associated with lower nadir CD4 in HIV-infected patients. B) Deformation-based morphometry (DBM) revealed an association between lower nadir CD4 and smaller volumes in the brainstem, thalamus, caudate, putamen, globus pallidus and right frontal lobe, and enlargement of the third ventricle in HIV-infected patients. (Images created with MRIcron http://people.cas.sc.edu/rorden/mricron/index.html).