A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects.
Title | A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Bandaru, VVenkata Ra, Mielke, MM, Sacktor, N, McArthur, JC, Grant, I, Letendre, S, Chang, L, Wojna, V, Pardo, C, Calabresi, P, Munsaka, S, Haughey, NJ |
Journal | Neurology |
Volume | 81 |
Issue | 17 |
Pagination | 1492-9 |
Date Published | 2013 Oct 22 |
ISSN | 1526-632X |
Keywords | Adult, AIDS Dementia Complex, Antiretroviral Therapy, Highly Active, Biomarkers, Ceramides, Cholesterol, Female, HIV Infections, Humans, Lipid Metabolism Disorders, Longitudinal Studies, Male, Predictive Value of Tests, Sphingolipids |
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. |
DOI | 10.1212/WNL.0b013e3182a9565e |
Alternate Journal | Neurology |
PubMed ID | 24027056 |
PubMed Central ID | PMC3888167 |
Grant List | 1U54RR026139-01A1 / RR / NCRR NIH HHS / United States 8U54MD007587 / MD / NIMHD NIH HHS / United States AA0017408 / AA / NIAAA NIH HHS / United States AG034849 / AG / NIA NIH HHS / United States DA61427 / DA / NIDA NIH HHS / United States HHSN271201000027C / / PHS HHS / United States HHSN271201000030C / / PHS HHS / United States MH071150 / MH / NIMH NIH HHS / United States MH075673 / MH / NIMH NIH HHS / United States MH077542 / MH / NIMH NIH HHS / United States MH22005 / MH / NIMH NIH HHS / United States MH61427 / MH / NIMH NIH HHS / United States NS56883 / NS / NINDS NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States S11NS46278 / NS / NINDS NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States U54NS43011 / NS / NINDS NIH HHS / United States |