Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation.

TitleAbdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation.
Publication TypeJournal Article
Year of Publication2015
AuthorsSattler, 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 AuthorsCHARTER Group
JournalJ Acquir Immune Defic Syndr
Volume68
Issue3
Pagination281-8
Date Published2015 Mar 1
ISSN1944-7884
KeywordsAdult, Aged, AIDS Dementia Complex, Cohort Studies, Cross-Sectional Studies, Cytokines, Female, HIV Infections, Humans, Inflammation, 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.

DOI10.1097/QAI.0000000000000458
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25469522
PubMed Central IDPMC4551458
Grant ListHHSN271201000036C / MH / NIMH NIH HHS / United States
HHSN271201000036C / / PHS HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
N01 MH22005 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R01 AG018169 / AG / NIA NIH HHS / United States
R01 AG18169 / AG / NIA NIH HHS / United States