The joint effect of aging and HIV infection on microstructure of white matter bundles

Abstract

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

Keywords: DTI; HIV; aging; tractography; white matter.

Conflict of interest statement

The authors report no conflict of interest.

PREVIOUS PRESENTATION OF THE ENCLOSED INFORMATION:

Preliminary findings similar to those reported herein and specific to the corpus callosum were presented as a poster at the 2017 meeting for the Organization for Human Brain Mapping. The citation is below:

1. Kuhn, T., Jin, Y., Huang, C., Kim, Y., Nir, T.M., Gullett, J.M., Jones, J., Singer, E.J., Shattuck, D., Jahanshad, N., Bookheimer, S.Y., Hinkin, C.H., Zhu, H., Thompson, P.M., Thames, A.D. The Joint Effect of Aging and HIV Infection on Integrity of the Corpus Callosum. Twenty‐third annual meeting of the Organization for Human Brain Mapping, Vancouver, British Columbia, Canada.

© 2019 Wiley Periodicals, Inc.

Figures

Figure 1

Depicting effect of advancing age on the CC (1), bilateral FRX (2), bilateral ATR (3), ILF (4), left ARC (5), and IFO (6) lower fractional anisotropy (a), and higher mean (b), axial (c), and radial diffusivity (d). The color bars correspond to the –log10 p‐values, where statistical significance was denoted as all –log values > 1.3 (p = .05), after multiple comparisons correction was applied across all fibers using false discovery rate [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Depicting effect of HIV group status on the CC (1), bilateral CST (2), bilateral CGC (3), left ARC (4), ILF (5), and IFO (6). The HIV+ group evidenced higher fractional anisotropy (a), and lower me/an (b), axial (c), and radial diffusivity (d). The color bars correspond to the –log10 p‐values, where statistical significance was denoted as all –log values >1.3 (p = .05), after multiple comparisons correction was applied across all fibers using false discovery rate [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Depicting interactive effect of HIV infection and advancing age on the CC (1), bilateral CST (2), left ARC (3), bilateral CGC (4), ILF (5), and IFO (6) lower fractional anisotropy (a), and higher mean (b), axial (c), and radial diffusivity (d). The color bars correspond to the –log10 p‐values, where statistical significance was denoted as all –log values > 1.3 (p = .05), after multiple comparisons correction was applied across all fibers using false discovery rate [Color figure can be viewed at http://wileyonlinelibrary.com]