Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

Abstract

Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

Increased brain-predicted aging in treated HIV disease

“…Previous research has associated nadir CD4 count 14,15 and duration of known HIV infection 13,17 with measures of brain structure, although not universally. 10,16,19 The nature of the participants in these studies differs substantively from ours. In general, HIV-positive individuals in our study were older, and all were effectively treated with cART and had higher CD4 counts.…”

“…Our findings favor the latter interpretation, as we found no relationship between brain-PAD score and chronological age or duration of HIV diagnosis. This fits with evidence from neuroimaging studies that have demonstrated independent effects of aging and HIV on the brain, 10,11,16,19,29 and does not support reports of accelerating effects. 12,21,30 However, these previous studies often included a preponderance of untreated individuals, those with detectable HIV viremia, or younger adults (i.e., <50 years old).…”

“…9 Deviations from a typical brain-aging trajectory (e.g., acceleration) may result from a brain injury, neurodegenerative disease, or, potentially, chronic HIV. While reduced brain volumes are frequently reported in HIV disease, 10–19 the evidence supporting accelerated brain aging is more equivocal. 10,20,21 These studies used macroscopic brain volume measures to correlate with chronological age.…”

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

“…Most notably, VBM analysis revealed reductions in WM tissue density in the brainstem and thalamus. These results are consistent with several prior studies that have reported volume loss in similar regions 7,11,13,29,30 , including diffusion tensor imaging studies that show loss of WM integrity in the thalamus and brainstem of HIV-infected patients 31,32 . The findings here support the hypothesis that subcortical structures are particularly vulnerable to the virus 33 , and add spatial detail regarding the distribution of atrophy.…”

Cognitive Impairment and Persistent CNS Injury in Treated HIV

“…The neuroanatomic structures involved in HIV infection are largely consistent across the various imaging modalities, with the most common affected brain regions being the frontal white matter (FWM) [38, 39], basal ganglia (BG) [42, 43, 38, 39], and the thalami [42]. The effect of HIV infection on frontostriatal circuitry was similarly reported by a meta-analysis combining six task-based functional MRI (fMRI) studies (n=105 HIV-infected and n=102 HIV-uninfected controls) where frontostriatal dysfunction correlated to degree of cognitive impairment, disease progression, and treatment effect [44].…”