Age exacerbates HIV-associated white matter abnormalities

Abstract

Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity.

Keywords: Aging; Diffusion tensor imaging; Fractional anisotropy; HIV; White matter; White matter hyperintensities.

Fig. 1

The HIV+ group shows greater increase in a whole-brain volumetric measure of white matter hyperintensities (WMH) with age vs. HIV- participants, depicting how age exacerbates HIV associated white matter damage. Results are displayed as best-fit lines with 95% confidence bands. Data are extrapolated for HIV+ individuals over age 65.

Fig. 2

White matter areas for which the age by HIV interaction was significant (p < .05). HIV+ participants showed stronger associations between older age and reduced FA compared to HIV- participants in the anterior corona radiata (β = -.142), posterior limbs of the internal capsules (β = -.198), and cerebral peduncles (β = -.184), showing that older age exacerbates HIV associated decreases of white matter integrity in these regions.

Fig. 3

Fractional anisotropy (FA) of white matter regions of interest as a function of age for HIV- and HIV+ groups. The HIV+ group shows greater FA decline with age in a the anterior corona radiata, b the posterior limbs of the internal capsules, and c the cerebral peduncles. Results are displayed as best-fit lines with 95% confidence bands. Data are extrapolated for HIV+ individuals over age 65.

Fig. 4

White matter regions of interest (ROIs) color-coded by the correlation with whole-brain white matter hyperintensities (WMH). Greater WMH were moderately correlated (-.204 ≤ r ≤ -.470) with lower fractional anisotropy in all ROIs and all relationships were significant (p < .05).