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Cortical and Subcortical Volumes on Magnetic Resonance Imaging Associated with HIV History and Current Disease Status
R Cohen1, Jaroslaw Harezlak*2, D Tate3, C Yiannoutosos2, M Taylor4, G Schifitto5, C Guttmann3, G Hana1, U Clark1, B Navia6, and HIV Neuroimaging Consortium
1Warren Alpert Med Sch, Brown Univ, Providence, RI, US; 2Indiana Univ Sch of Med, Indianapolis, US; 3Harvard Med Sch, Boston, MA, US; 4Univ of California, San Diego Med Ctr, US; 5Univ of Rochester Sch of Med, NY, US; and 6Tufts Univ Sch of Med, Boston, MA, US
Background: Despite
reduced prevalence of HIV-associated dementia in the HAART era, HIV continues
to affect the brains of patients with chronic infection. The effects of duration
of HIV infection in the aging brain relative to the severity of current and
prior immune system dysfunction remains unresolved. We hypothesized that CD4 nadir,
illness duration, and age would be associated with reduced cortical volumes.
Methods: Cross-sectional analyses were conducted on MPRAGE brain
MRI from HIV+ patients (n = 82). Brain segmentation by voxel-based
morphometry (SPM-5), with AAL to determine frontal, parietal, temporal,
occipital, caudate, putamen, and hippocampal, and total gray and white matter,
and ventricular volumes was performed. Current CD4, CD4 nadir, plasma viral
load, ADC stage, time since HIV diagnosis, age, education, gender, and race were
entered as independent measures into linear regression analyses with each brain
ROI as a dependent variable. Final models were selected by minimizing Akaike
Information Criterion (AIC), which balances model fit and complexity.
Results: Smaller frontal (adj. R2 = 0.07) and
temporal (adj. R2 = 0.15) volumes were associated with CD4 nadir
less than 50 and greater duration of infection. Smaller parietal volume (adj. R2
= 0.15) was associated with longer time since diagnosis and ADC stage <1.
Hippocampal volume (adj. R2 = 0.08) was associated with all 3 of
these variables. Caudate volume (adj. R2 = 0.08) was associated with
detectable current plasma viral load and ADC stage >1. The putamen was not
significantly associated with any HIV variable. Total white matter volume (adj.
R2 = 0.08) was associated with CD4 nadir, while ventricular volume (adj.
R2 = 0.09) was associated with ADC stage and longer HIV duration.
Age did not contribute significantly to any of these associations.
Conclusions: Caudate volume was associated with current
plasma viral load, as expected based on evidence from the pre-HAART. In
contrast, HIV severity and duration related to reduced cortical and hippocampal
volumes, suggesting that patients who suffered prior severe immune dysfunction may
eventually experience cortical and hippocampal changes even in the context of
HAART. This is noteworthy, as these brain areas were not viewed as primary
sites of HIV infection in the past, suggesting an evolution of cortical disturbances
with chronic HIV infection that requires further investigation.
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