Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

Abstract

Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36).Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses.HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. There were no associations between neurometabolites and neuronal damage markers in blood or CSF.Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.

FIGURE 1

Exemplar planning of chemical shift imaging (CSI), superimposed on a 3D-T1-weighted image. Based on the 3D-T1-weighted scan (A), gray matter (GM), and white matter (WM) segmentation was performed within the CSI field-of-view (B). Estimated metabolite levels (C) were averaged within all GM and WM voxels to obtain mean GM and WM values (D). CSI = chemical shift imaging, GM = gray matter, WM = white matter.