Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation.
Title | Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Sattler, FR, He, J, Letendre, S, Wilson, C, Sanders, C, Heaton, R, Ellis, R, Franklin, D, Aldrovandi, G, Marra, CM, Clifford, D, Morgello, S, Grant, I, J McCutchan, A |
Corporate Authors | CHARTER Group |
Journal | J Acquir Immune Defic Syndr |
Volume | 68 |
Issue | 3 |
Pagination | 281-8 |
Date Published | 2015 Mar 01 |
ISSN | 1944-7884 |
Keywords | Adult, Aged, AIDS Dementia Complex, CHARTER, Cohort Studies, Cross-Sectional Studies, Cytokines, Female, HIV Infections, Humans, Inflammation, Internal, Male, Middle Aged, Obesity, Abdominal, Young Adult |
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. |
DOI | 10.1097/QAI.0000000000000458 |
Alternate Journal | J Acquir Immune Defic Syndr |
PubMed ID | 25469522 |
PubMed Central ID | PMC4551458 |
Grant List | R01 AG018169 / AG / NIA NIH HHS / United States K24 MH097673 / MH / NIMH NIH HHS / United States R01 AG18169 / AG / NIA NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States N01 MH022005 / MH / NIMH NIH HHS / United States |