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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).

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.

SUBMITTER: Sattler FR 

PROVIDER: S-EPMC4551458 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Sattler Fred R FR   He Jiaxiu J   Letendre Scott S   Wilson Cara C   Sanders Chelsea C   Heaton Robert R   Ellis Ronald R   Franklin Donald D   Aldrovandi Grace G   Marra Christina M CM   Clifford David D   Morgello Susan S   Grant Igor I   McCutchan J Allen JA  

Journal of acquired immune deficiency syndromes (1999) 20150301 3


<h4>Objective</h4>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).<h4>Design</h4>Cross-sectional.<h4>Setting</h4>Six Academic Centers.<h4>Participants</h4>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).<h4>Outcome measures</h  ...[more]

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