Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally suppressed people with HIV

OBJECTIVES: Virally suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used PET to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework. DESIGN: Cross-sectional investigation in VS-PWH ( n  = 25) versus HIV-uninfected individuals ( n  = 18) of cognitive control and declarative memory, as well as [ 11 C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest (ROI). METHODS: Group differences in [ 11 C]DPA-713 binding ( VT ) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype. RESULTS: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [ 11 C]DPA-713 VT across cognitive control regions [unstandardized beta coefficient reflecting mean difference [ B ] = 0.23, SE = 0.11, 95% confidence interval (CI) 0.01-0.45, P  = 0.04] and declarative memory regions ( B   =  0.24, SE = 0.11, 95% CI 0.02-0.45, P  = 0.03). Higher log [ 11 C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [ 11 C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory. CONCLUSION: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.