Greater than age-related changes in brain diffusion of HIV patients after 1 year

Abstract

Chronic infection with HIV is associated with neuroinflammation. Prior diffusion tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and decreased fractional anisotropy (FA) in the white matter (WM) and subcortical brain regions of HIV patients. The current study aims to detect whether there are greater than age-related brain changes in HIV patients after a 1-year follow-up period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV-seronegative (SN) controls were evaluated, with neuropsychological tests and DTI, at baseline and after 1 year. MD and FA in the genu and splenium of the corpus callosum and in six other subcortical and white matter regions were evaluated bilaterally. Compared to SN controls, HIV subjects had significantly higher MD in the frontal WM (p = 0.0104) and lower FA in the parietal WM (p = 0.006). After 1 year, HIV subjects showed increase in MD in frontal and parietal WM, putamen, and genu; HIV subjects also showed greater increased genu diffusion than SN controls (p = 0.005). Changes in global cognitive deficit score correlated with changes in MD in the genu and FA in the parietal and frontal WM and putamen (multiple regression, p = 0.0008). Lastly, normal age-dependent changes in frontal WM diffusion and FA in genu and putamen were not observed in HIV subjects. Since increased MD may reflect increased neuroinflammation, our findings suggest greater than normal age-related inflammatory changes in the genu of these HIV patients, which may contribute to the cognitive deficits. Measurements of MD in the genu may be useful for monitoring disease progression in HIV brain infection.

Figures

Fig. 1

Axial DTI showing the brain regions evaluated

Fig. 2

Mean diffusivity in SN and HIV subjects at baseline and after 1 year (mean±SE). Compared to SN, HIV subjects showed greater 1-year increases in MD in the genu (top left). Additionally, significant increases in MD were observed in the putamen, frontal, and parietal white matter regions only in the HIV subjects but not in the SN subjects

Fig. 3

Age dependence of MD and FA in various brain regions in the two subject groups. Significant age-dependent changes are observed only in the SN subjects but not in the HIV subjects, with trends for significant group difference in the genu FA (p=0.056), frontal white matter MD (p=0.18), and the putamen FA (p=0.11)

Fig. 4

Linear regression analyses showing changes in the global deficit scores in relation to changes in MD in genu (top left), FA in the frontal white matter (bottom left), and FA in the putamen (top right) in both subject groups. Multiple regression analyses showed that GDS is associated with change in the genu MD (p=0.0038), change in parietal white matter FA (p=0.049), change in frontal white matter FA (p=0.0037), and change in putamen FA (p=0.0007)