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J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):281-8. doi: 10.1097/QAI.0000000000000458.

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

Author information

  • 1*Department of Medicine, Division of Infectious Diseases, University of Southern California, Los Angeles, CA; †Department of Preventative Medicine, University of Southern California, Los Angeles, CA; Departments of ‡Medicine, and Departments of §Psychiatry, and ‖Neurology, University of California San Diego, San Diego, CA; ¶Department of Medicine, Division of Infectious Diseases and Clinical Immunology, University of Colorado, Medicine, Denver, CO; #Department of Pediatrics, Division of Infectious Disease, Children's Hospital Los Angeles, Los Angeles, CA; **Department of Neurology, Department of Medicine, Division of Allergy, and Infectious Diseases, University of Washington, Seattle, WA; ††Department of Neurology and Medicine, Washington University, St. Louis, MO; and ‡‡Department of Neurology, Pathology, and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY.

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.

PMID:
25469522
[PubMed - indexed for MEDLINE]
PMCID:
PMC4551458
Free PMC Article
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