Factors affecting brain structure in men with HIV disease in the post-HAART era

Abstract

Introduction: The purpose of this study was to characterize brain volumetric differences in HIV seropositive and seronegative men and to determine effects of age, cardiovascular risk, and HIV infection on structural integrity.

Methods: Magnetic resonance imaging was used to acquire high-resolution neuroanatomic data in 160 men aged 50 years and over, including 84 HIV seropositive and 76 seronegative controls. Voxel-based morphometry was used to derive volumetric measurements at the level of the individual voxel. Data from a detailed neuropsychological test battery were recombined into four summary scores representing psychomotor speed, visual memory, verbal memory, and verbal fluency.

Results: Both age and HIV status had a significant effect on both gray matter (GM) and white matter (WM) volume. The age-related GM atrophy was primarily in the superior temporal and inferior frontal regions; the HIV-related GM loss included the posterior and inferior temporal lobes, the parietal lobes, and the cerebellum. Among all subjects, the performance on neuropsychological tests, as indexed by a summary variable, was related to the volume of both the GM and WM. Contrary to our predictions, the CVD variables were not linked to brain volume in statistically adjusted models.

Conclusion: In the post-HAART era, having HIV infection is still linked to atrophy in both GM and WM. Secondly, advancing age, even in this relatively young cohort, is also linked to changes in GM and WM volume. Thirdly, CNS structural integrity is associated with overall cognitive functions, regardless of the HIV infection status of the study volunteers.

Fig. 1

The results of the VBM analysis of gray matter projected onto the single-subject template of the cortical surface from SPM2. The effects of age are shown in the right-hand columns, and the effects of HIV disease in the left-hand columns. Both variables were entered into the same analysis simultaneously, with total intra-cranial volume as a covariate. False discovery rate=p<.05, with an extent threshold of 100 voxels. The regions with the hotter colors are those with the greatest amount of atrophy attributable to age or HIV status

Fig. 2

The results of the VBM analysis of the white matter atrophy projected onto the mean whole brain image created from the seronegative subjects. For all study participants, atrophy was significantly associated with advancing age, but not with HIV status. False discovery rate=p<.05, with an extent threshold of 100 voxels. The regions with the hotter colors are those with the greatest amount of white matter atrophy attributable to age

Fig. 3

WM atrophy associated with lower scores on the neuropsychological tests. These regions were in the same WM regions as those observed for the aging effect, but with less spatial extent. The left-hand image shows a “glass brain” view in which all voxels are visible in each of the three perspectives. The images on the right show the areas of significant association between white matter volume and test performance