Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation. (1st March 2015)

• Record Type: Journal Article
• Authors: Sattler, Fred R.; He, Jiaxiu; Letendre, Scott; Wilson, Cara; Sanders, Chelsea; Heaton, Robert; Ellis, Ronald; Franklin, Donald; Aldrovandi, Grace; Marra, Christina M.; Clifford, David; Morgello, Susan; Grant, Igor; McCutchan, J. Allen
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 68:Number 3(2015)
• Publication Date: 2015-03-01
• Subjects: abdominal obesity -- HIV-associated neurocognitive disorder -- inflammation and immune activation -- global deficit score -- sCD40L -- sCD14; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000000458
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : 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 (ρ = 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 (ρ = 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. Abstract : Supplemental Digital Content is Available in the Text.