Age-Accelerated Increase of White Matter Hyperintensity Volumes Is Exacerbated by Heavy Alcohol Use in People Living With HIV

Abstract

Background: Antiretroviral treatment has enabled people living with HIV infection to have a near-normal life span. With longevity comes opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether HIV infection, even if successfully treated, or AUD alone results in signs of accelerated white matter aging and whether HIV+AUD comorbidity further accelerates brain aging.

Methods: Longitudinal magnetic resonance imaging-FLAIR data were acquired over a 15-year period from 179 control individuals, 204 participants with AUD, 70 participants with HIV, and 75 participants with comorbid HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized, and their functional relevance was examined with cognitive and motor testing.

Results: The 3 diagnostic groups each had larger WMH volumes than the control group. Although all 4 groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than control individuals; the comorbid group showed faster acceleration than the HIV-only group. Sex and HIV infection length, but not viral suppression status, moderated acceleration. Correlations emerged between WMH volumes and attention/working memory and executive function scores of the AUD and HIV groups and between WMH volumes and motor skills in the 3 diagnostic groups.

Conclusions: Even treated HIV can show accelerated aging, possibly from treatment sequelae or legacy effects, and notably from AUD comorbidity. WMH volumes may be especially relevant for tracking HIV and AUD brain health because each condition is associated with liability for hypertensive processes, for which WMHs are considered a marker.

Keywords: Aging; Alcohol; Brain; Cognition; HIV infection; White matter hyperintensity.

Figure 1.

Axial images from FLAIR images acquired in an HIV infected woman examined when she was age 49 and then 54 years old. Note the enlargement of the WMHs delineated in red outlining. Examples of periventricular WMH (yellow arrows) and deep WMH tissue (red arrows) are indicated.

Figure 2.

Top row: Box plots and data points of volumes of the Total (left column), PVWMH (middle column), and DWMH (right column) volumes for each participant’s data for all visits. Controls (gray), AUD (blue), HIV (green), and HIV+AUD (red). Bottom 12 spaghetti plots: Total, PVWMH, and DWMH volumes for individual from each study group. Data and regression lines of the three diagnostic groups are plotted on the control regression lines for comparison. The diagnostic group-by-control interaction results are provided in the upper left corner of the plots. Although all three diagnostic groups had larger WMH volumes in each region, only the two HIV groups showed significant interactions with controls over age, indicating age accelerations.

Figure 3.

Longitudinal data and regression lines for PVWMH volumes of individuals with HIV (green) and HIV+AUD (red). The HIV+AUD group shows a faster volume acceleration over age than the HIV group.

Figure 4.

Box plots overlaid on the scatterplots of Z-scores for the five domain composite scores and the mean domain scores, each of which was age, sex, and education adjusted on the controls and acquired at initial study time. The four study groups are color coded.

Figure 5.

Linear regressions and 95% confidence intervals for significant correlations between mean composite Z-scores and Total WMH volumes at initial study time, indicating that larger WMH volumes correlated with poorer performance in each group. Additional functional-WMH volume correlations appear in Tables 3 and 4.