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

TitleA lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects.
Publication TypeJournal Article
Year of Publication2013
AuthorsBandaru, VVenkata Ra, Mielke, MM, Sacktor, N, McArthur, JC, Grant, I, Letendre, S, Chang, L, Wojna, V, Pardo, C, Calabresi, P, Munsaka, S, Haughey, NJ
JournalNeurology
Volume81
Issue17
Pagination1492-9
Date Published2013 Oct 22
ISSN1526-632X
KeywordsAdult, AIDS Dementia Complex, Antiretroviral Therapy, Highly Active, Biological Markers, 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.

DOI10.1212/WNL.0b013e3182a9565e
Alternate JournalNeurology
PubMed ID24027056
PubMed Central IDPMC3888167
Grant List1U54RR026139-01A1 / 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