Effect of aging on brain metabolism in antiretroviral-naive HIV patients

Abstract

Normal aging as well as HIV infection may lead to inflammatory changes and injury to the brain; however, it is unclear if and how these processes interact. The goal of this pilot study was to evaluate the interaction between aging and HIV infection in the brain using proton magnetic resonance spectroscopy (H-MRS). Analyses of covariance (ANCOVA) were performed to determine the effects of HIV and age, and their interaction, on MRS variables. Forty-six HIV patients naive to antiretroviral medications and 58 seronegative control subjects were examined using localized H-MRS in the frontal gray matter, frontal white matter and basal ganglia, and metabolite concentrations were determined. Compared with seronegative controls, HIV-positive subjects showed additional and marked increases in the concentration of glial markers, choline-containing compounds (seronegative controls +2%/decade; HIV-positive subjects +10%/decade) and myoinositol (seronegative controls +3%/decade; HIV-positive subjects +12%/decade), with aging in the frontal white matter. In the basal ganglia, N-acetyl compounds and total creatine decreased with age only in HIV patients (N-acetyl compounds -3.7%/decade; creatine -4%/decade). ANCOVA showed significant interaction effects between HIV and aging on the metabolites in the basal ganglia (N-acetyl peak P = 0.03; creatine P = 0.04) and in the frontal white matter (interaction: choline-containing compounds P = 0.002; myoinositol P = 0.007). In the basal ganglia, HIV infection appeared to induce neuronal damage or loss beyond that observed in normal aging. In the frontal white matter, HIV infection seemed to exacerbate glial activation beyond that observed in normal aging.