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

作者：Bandaru Veera Venkata Ratnam; Mielke Michelle M; Sacktor Ned; McArthur Justin C; Grant Igor; Letendre Scott; Chang Linda; Wojna Valerie; Pardo Carlos; Calabresi Peter; Munsaka Sody; Haughey Norman J^*

来源：Neurology, 2013, 81(17): 1492-1499.

DOI：10.1212/WNL.0b013e3182a9565e

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.

• 出版日期2013-10-22