Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation

Objective:We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and central nervous system immunoinflammatory mediators contributes to neurocognitive impairment (NCI).Design:Cross-sectional.Setting:Six Academic Centers.Participants:One hundred fifty-two patients with plasma HIV RNA <1000 copies per milliliter had clinical evaluations and cognitive function quantified by global deficit scores (GDS).Outcome Measures:GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9.Results:WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 ( = 0.39, P = 0.005). IL-6 correlated with GDS only if WC was 99 cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest ( = 0.60, P < 0.0001). Across 3-5 visits within 1 year of the index visit, GDS remained worse in patients with IL-6 levels in the high versus low tertile (P = 0.02). Path analysis to explore potential mediators of NCI produced a strong integrated model for patients in the high CSF sCD40L tertile. In this model, WC affected GDS both directly and through a second path that was mediated by IL-6. Inclusion of plasma sCD14 levels strengthened the model. NCI was more common in men and for individuals with components of the metabolic syndrome.Conclusions:Neurocognitive function was significantly linked to abdominal obesity, systemic inflammation (high IL-6), and immune activation in plasma (high sCD14) and CSF (high sCD40L). Abdominal obesity, inflammation, and central nervous system immune activation are potential therapeutic targets for NCI in HIV-positive patients.