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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1492-1499
Number of pages8
JournalNeurology
Volume81
Issue number17
DOIs
StatePublished - Oct 22 2013

ASJC Scopus subject areas

  • Clinical Neurology

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