Objective
We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI).
Design
Cross-sectional
Setting
Six Academic Centers
Participants
152 patients with plasma HIV RNA <1,000copies/ml 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 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year 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 via 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
NC 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 CNS immune activation are potential therapeutic targets for NCI in HIV+ patients.