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 CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Design Cross-sectional Setting Six Academic Centers Participants 152 patients with plasma HIV RNA <1,000copies/ml 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 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year 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 via 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 NC 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 CNS immune activation are potential therapeutic targets for NCI in HIV+ patients.

Body mass index, inflammatory biomarkers and neurocognitive impairment in HIV-infected persons

“…McCutchan et al, 2012, found a protective effect of increased BMI on an overall global measure of neurocognitive impairment, whereas higher waist circumference, was predictive of neurocognitive impairment after correcting for a diagnosis of AIDS or diabetes and serum triglycerides among 130 participants of the CHARTER study(McCutchan et al, 2012; Sattler et al, 2014). However, this study did not assess specific cognitive domains by BMI status.…”

Changes in weight and weight distribution across the lifespan among HIV-infected and -uninfected men and women

“…These changes in WC in those more than 60 years with a leveling off of BMI suggest a concomitant loss of lean mass (an estimate of skeletal muscle) that may have important clinical consequences in an aging population: changes in WC are highly correlated with changes in trunk fat by dual-energy absorptiometry and with visceral adipose tissue area by computed tomography scan (Priya Bhagwat, et al; Measurement of Abdominal Fat Changes in HIV-Infected Individuals Initiating Therapy ; Abstract #704, presented at Conference on Retroviruses and Opportunistic Infections; Boston, MA 2/2016). Moreover, central obesity has negative metabolic effects and has been associated with increased mortality [24] and neurocognitive impairment, [25] in addition to fatty liver disease [26] and liver stiffness among HIV-infected individuals. [27] …”

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

“…In HIV-infected persons, poorer neurocognitive function has been associated with both increased waist circumference (a marker of visceral adiposity[85])[86] and obesity[87]. Among a subset of middle-aged, HIV-infected and at risk HIV-uninfected women in the Womens Interagency HIV Study, higher leptin levels (indicative of higher adiposity) correlated strongly with poorer neurocognitive testing performance[88].…”