Independent effects of HIV, aging, and HAART on brain volumetric measures

Abstract

Background: Neurocognitive impairment remains prevalent in HIV-infected (HIV+) individuals despite highly active antiretroviral therapy (HAART). We assessed the impact of HIV, HAART, and aging using structural neuroimaging.

Methods: Seventy-eight participants [HIV- (n = 26), HIV+ on stable HAART (HIV+/HAART+; n = 26), HIV+ naive to HAART (HIV+/HAART-; n = 26)] completed neuroimaging and neuropsychological testing. A subset of HIV+ subjects (n = 12) performed longitudinal assessments before and after initiating HAART. Neuropsychological tests evaluated memory, psychomotor speed, and executive function, and a composite neuropsychological score was calculated based on normalized performances (neuropsychological summary Z score, NPZ-4). Volumetrics were evaluated for the amygdala, caudate, thalamus, hippocampus, putamen, corpus callosum, and cerebral gray and white matter. A 3-group 1-way analysis of variance assessed differences in neuroimaging and neuropsychological indices. Correlations were examined between NPZ-4 and volumetrics. Exploratory testing using a broken-stick regression model evaluated self-reported duration of HIV infection on brain structure.

Results: HIV+ individuals had significant reductions in brain volumetrics within select subcortical regions (amygdala, caudate, and corpus callosum) compared with HIV- participants. However, HAART did not affect brain structure as regional volumes were similar for HIV+/HAART- and HIV+/HAART+. No association existed between NPZ-4 and volumetrics. HIV and aging were independently associated with volumetric reductions. Exploratory analyses suggest caudate atrophy due to HIV slowly occurs after self-reported seroconversion.

Conclusions: HIV associated volumetric reductions within the amygdala, caudate, and corpus callosum occurs despite HAART. A gradual decline in caudate volume occurs after self-reported seroconversion. HIV and aging independently increase brain vulnerability. Additional longitudinal structural magnetic resonance imaging studies, especially within older HIV+ participants, are required.

Figure 1

Using Freesurfer the corpus callosum, amygdala, caudate, thalamus, and putamen were determined for each subject. * Denotes the p-value for brain regions that were significantly different after a one-way analysis of variance (correcting for multiple comparisons). All error bars are presented as quartiles.

Figure 2. Effects of HIV and aging within the caudate

For both HIV+ and HIV− subjects a significant reduction in caudate volume was seen with aging. Overall HIV+ participants had a greater atrophy than HIV−. For this analysis, HIV+/HAART+ and HIV+/HAART− were combined into a single group as similar results were seen for the two subgroups.

Figure 3. Effects of self-reported duration of HIV infection on caudate volume

HIV− are represented at T=0. This group can be seen as subjects just prior to HIV infection. The upper hashed line is the mean log volume for HIV−. The lower dotted line is the mean log-volume for chronically infected HIV. The dashed smooth line (lowess) and the solid broken-stick line (piecewise linear model) show the progression of caudate atrophy from the HIV− status to the chronically infected HIV+ status. Approximately 160 months (~13 years) is required for this transition. A large amount of variability exists. All lines were age-adjusted.