TY - JOUR
T1 - A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects
AU - Bandaru, Veera Venkata Ratnam
AU - Mielke, Michelle M.
AU - Sacktor, Ned
AU - McArthur, Justin C.
AU - Grant, Igor
AU - Letendre, Scott
AU - Chang, Linda
AU - Wojna, Valerie
AU - Pardo, Carlos
AU - Calabresi, Peter
AU - Munsaka, Sody
AU - Haughey, Norman J.
PY - 2013/10/22
Y1 - 2013/10/22
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0b013e3182a9565e
DO - 10.1212/WNL.0b013e3182a9565e
M3 - Article
C2 - 24027056
AN - SCOPUS:84887253206
SN - 0028-3878
VL - 81
SP - 1492
EP - 1499
JO - Neurology
JF - Neurology
IS - 17
ER -