Date Published:
2015 Mar 01
Publication Type:
Journal Article
Authors:
Secondary:
J Acquir Immune Defic Syndr
Volume:
68
Pagination:
281-8
Issue:
3
PMID:
25469522
URL:
https://pubmed.ncbi.nlm.nih.gov/25469522
DOI:
10.1097/QAI.0000000000000458
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:
<p>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.</p>