The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

Abstract

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus in 81 participants ranging in age from 24 – 76 including 59 HIV+ individuals and 22 HIV-seronegative controls. T1-weighted MRI underwent a pre-processing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus and thalamus. Of greatest interest, an age*HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age*HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study

“…25 For episodic memory, the neuroanatomical referent is the hippocampus, wherein dysfunction and atrophy have been noted to occur independently with both aging 26 and HIV infection 27 as well as in a deleterious interaction between aging and HIV infection. 28 Several studies have documented these regions to be of particular concern for damage in the setting of older persons with HIV infection. A critical review reported that HIV infection has been associated with greater than age-related brain atrophy in the basal ganglia and hippocampus.…”

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

“…However, the literature disagrees on whether there is an interactive relationship between HIV infection and aging in cognitively unimpaired patients (Holt, Kraft-Terry, & Chang, 2012). Some scientists contend that there is no interactive or synergistic effect of HIV and aging on the brain Valcour et al, 2004a), whereas others contend that HIV infection accelerates brain aging (Kuhn et al, 2016;Morgan, Lee, & Nyagode, 2011;Sacktor et al, 2010;Vance, McGuinness, Musgrove, Orel, & Fazeli, 2011). We suggest here that the previous inability to detect significant Age*HIV interactive effects in WM microstructure may be due to methodological differences (including neuroimage processing, statistical analysis, and sample size) rather than the lack of an Age*HIV interaction.…”

An Augmented Aging Process in Brain White Matter in HIV

“…Although no significant relationships between BAG and nadir CD4+ or HIV disease duration were reported, the authors investigated white matter volume, rather than white matter microstructure (using DTI) and in a sample of HIV+ participants with undetectable viral loads. Thus, it is unclear to which degree findings of "attenuated brain aging" in HIV 9,11,12 may be mediated by primary or secondary processes related to the infection. It is also unclear what effects these processes may have on WM microstructure.…”