White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV

Abstract

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV−; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV− groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV− group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.

The Use of Visual Rating Scales to Quantify Brain MRI Lesions in Patients with HIV Infection

“…Further supporting their validity, all three scales were also associated with neurocognitive impairment, as reflected by the global T score derived from a comprehensive neuropsychological assessment. These data are consistent with previous studies reporting associations between WMH and global neurocognitive ability in HIV . Additionally, we report the novel finding that WMH burden is associated with memory functions in HIV patients, which aligns with data from non‐HIV older adult samples with memory complaints …”

“…Hence, there is large overlap between the clinical correlates of CSVD and WMH in HIV‐infected cohorts. Furthermore, increases in WMH have observable functional consequences in HIV patients, including neurocognitive difficulties, particularly in the domains of executive function and psychomotor speed …”

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

“…43 Volumetric reductions are correlated to the frequency of white matter lesions thought to be due to SVID in HIV-uninfected study groups, providing another underlying factor that may be disproportionately present in the setting of HIV. 34,42 Our findings in both grey and white matter suggest SVID alone is insufficient to explain our findings.…”

“…25,34 Similarly, we employed regression models to examine clinical variables including duration of HIV, nadir and proximal CD4 counts. These analyses comprised of two different levels, first assessing relationships between baseline volume and all clinical variables simultaneously, correcting for age, sex and TIV.…”

An augmented aging process in brain white matter in HIV

“…Additionally, BAG outperformed each individual DTI metric in its ability to discriminate between HIV+ and HIV− participants and demonstrate the effect of HIV infection on advancing brain white matter age. BAG also may be more useful than, or at the very least a meaningful compliment to, hyper/hypo-intense lesion volume and count which has been shown to relate to HIV infection and cognitive performance, but not to HIV clinical variables or HIV-associated aging 41, 42, 43 . Additionally, BAG is a relatively easy metric to understand and thus it circumvents the cumbersome and difficult to interpret multivariate score often used with DTI metrics which are inherently difficult to connect to clinical variables.…”