A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects.

Abstract

OBJECTIVE:

In this multicenter cohort study, we sought to identify prognostic and associative metabolic indicators for HIV-associated neurocognitive disorders (HAND).

METHODS:

A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples collected from 7 different performance sites across the mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected individuals with longitudinal clinical and cognitive testing data and cognitively normal HIV-negative healthy controls.

RESULTS:

At baseline, HIV+ subjects could be differentiated from HIV- controls by reductions in a single ceramide species and increases in multiple forms of cholesterol. Perturbations in cholesterol metabolism and ceramide were influenced by combined antiretroviral therapy (cART) use. There were no cross-sectional baseline differences in any lipid metabolite when HIV+ subjects were grouped according to cognitive status. However, a single sphingolipid metabolite and reduced levels of esterified cholesterols were prognostic indicators of incident cognitive decline. Longitudinal patterns of these disturbances in sphingolipid and sterol metabolism suggest that a progressive disorder of lipid metabolism that is similar to disorders of lipid storage may contribute to the pathogenesis of HAND.

CONCLUSIONS:

These findings suggest that HIV infection and cART are independently associated with a CNS metabolic disturbance, identify surrogate markers that are prognostic for cognitive decline, and implicate a lipid storage-like disorder in the progression of HAND.

• Authors: Veera Venkata Ratnam Bandaru, Michelle M Mielke, Ned Sacktor, Justin C McArthur, Igor Grant, Scott Letendre, Linda Chang, Valerie Wojna, Carlos Pardo, Peter Calabresi, Sody Munsaka, Norman J Haughey
• Journal: Neurology (Neurology) Vol. 81 Issue 17 Pg. 1492-9 (Oct 22 2013) ISSN: 1526-632X [Electronic] United States
• PMID: 24027056 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Ceramides
• Sphingolipids
• Cholesterol

Topics

• AIDS Dementia Complex (cerebrospinal fluid, etiology, physiopathology)
• Adult
• Antiretroviral Therapy, Highly Active (adverse effects)
• Biomarkers (cerebrospinal fluid)
• Ceramides (cerebrospinal fluid)
• Cholesterol (cerebrospinal fluid)
• Female
• HIV Infections (cerebrospinal fluid, complications, drug therapy)
• Humans
• Lipid Metabolism Disorders (cerebrospinal fluid, complications, etiology)
• Longitudinal Studies
• Male
• Predictive Value of Tests
• Sphingolipids (cerebrospinal fluid)