title: Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation.
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).
  
  
  METHODS
  Cross-sectional.
  
  
  METHODS
  Six Academic Centers.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: *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.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Sattler
authors.forename: Jiaxiu
authors.initials: J
authors.lastname: He
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Cara
authors.initials: C
authors.lastname: Wilson
authors.forename: Chelsea
authors.initials: C
authors.lastname: Sanders
authors.forename: Robert
authors.initials: R
authors.lastname: Heaton
authors.forename: Ronald
authors.initials: R
authors.lastname: Ellis
authors.forename: Donald
authors.initials: D
authors.lastname: Franklin
authors.forename: Grace
authors.initials: G
authors.lastname: Aldrovandi
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: David
authors.initials: D
authors.lastname: Clifford
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
mesh_terms: D015526:AIDS Dementia Complex / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications*; D055815:Young Adult
chemical_list: D016207:Cytokines