Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age

Abstract

Background: Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity.

Methods: Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects. This design enabled examination of independent and combined effects of HIV infection and alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]-defining events, hepatitis C infection, age) on regional brain volumes derived from T1-weighted magnetic resonance images.

Results: Brain volumes, expressed as Z scores corrected for intracranial volume and age, were measured in 20 tissue and 5 ventricular and sulcal regions. The most profound and consistent volume deficits occurred with alcohol use disorders, notable in the cortical mantle, insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes than control subjects. HIV disease-related factors associated with greater volume abnormalities included CD4 cell count nadir, clinical staging, history of AIDS-defining events, infection age, and current age. Longer sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities in both alcohol groups.

Conclusions: Having HIV infection with alcoholism and AIDS had an especially poor outcome on brain structures. That longer periods of sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities encourages the inclusion of alcohol recovery efforts in HIV/AIDS therapeutic settings.

Figure 1

Top panel in gray scale: Axial slices from the SRI24 atlas of the superior (top left) to inferior (bottom right) brain regions. Bottom panel in color: 6 bilateral cortical and 4 allocortical gray matter regions and 5 subcortical tissue regions overlaid on the SRI24 atlas and color-coded by structure name.

Figure 2

Mean±S.E.M of each regional brain tissue volume, expressed as ICV- and age- corrected Z-scores, for each of the four study groups. Low scores are in the direction of tissue deficits. * denotes significant differences from controls (Scheffé posthoc tests p≤.05).

Figure 3

Mean±S.E.M of each regional ventricular and sulcal volume, expressed as ICV- and age-corrected Z-scores, for each of the four study groups. High scores are in the direction of CSF-space expansion. * denotes significant differences from controls (Scheffé posthoc tests p≤.05).

Figure 4

Mean±S.E.M of each regional brain volume, expressed as ICV- and age- corrected Z-scores, for each of the patient study groups divided by presence or absence of an AIDS-defining event. Low scores for tissue volumes and high scores for CSF volumes are in the direction of abnormality. * denotes significant differences from controls (t-tests p≤.05).

Figure 5

Linear regressions showing older age at MRI and older age at HIV-infection onset correlating with anterior cingulate ICV- and age-corrected Z-scores in the HIV-only group.