A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects
Open accessAbstract
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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Efficacy of statins on neurocognitive impairment has not been as promising in clinical studies.
“Despite the encouraging data from animal studies, the efficacy of statins on neurocognitive impairment has not been as promising in clinical studies [82].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [82]
The Results (page not available in our copy) report that, among 19 participants taking a statin at baseline, statin use was not associated with worsening or improvement in cognitive status. This supports a limited lack-of-benefit observation in people with HIV, but the paper does not establish statin efficacy across clinical studies or compare those findings with animal studies. (LLM, conf=0.84)
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Dickens, A. M., Tovar-y-Romo, L. B., Yoo, S.-W., Trout, A. L., Bae, M., Kanmogne, M., Megra, B., Williams, D. W., Witwer, K. W., Gacias, M., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aai7696 · Cited by 285 · see citing works
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“In this context, disruptions in peripheral cholesterol flux are also observed in HIV-infected individuals, thereby contributing to increased risk of atherosclerosis and cardiovascular disease (Bandaru et al. 2013; Feeney et al. 2013; Mujawar et al. 2006).”
BackgroundMohseni Ahooyi, T., Shekarabi, M., Torkzaban, B., Langford, T. D., Burdo, T. H., Gordon, J., Datta, P. K., Amini, S., & Khalili, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-34539-9 · Cited by 29 · see citing works
Cheng, Y., Jung, J., Guo, L., Shuboni-Mulligan, D. D., Chen, J.-F., Hu, W., & Guo, M.-L. (2025) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2024.09.011 · Cited by 16 · see citing works
- Authors
- Bandaru, V. V. R., Mielke, M. M., Sacktor, N., McArthur, J. C., Grant, I., Letendre, S., Chang, L., Wojna, V., Pardo, C., Calabresi, P., Munsaka, S., & Haughey, N. J.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- ORCID
- Venue
- Neurology
- Published
- 2013-10-22
- Volume
- 81
- Issue
- 17
- Pages
- 1492-1499
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3888167
- OpenAlex
- W2011442035
- Cited by
- 61
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 4 · 2014: 10 · 2013: 2
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01mh22005-16-0-1, 1u54rr026139-01a1)
- National Institute on Alcohol Abuse and Alcoholism (R01AA017408, AA0017408)
- National Institute on Aging (R21AG034849, AG034849)
- National Institute of Mental Health (U01MH083506, HHSN271201000030C, MH 22005, N01MH022005, MH071150, MH077542, HHSN271201000027C, U24MH100928, R01MH071150, R01MH061427, MH075673, R01MH077542, MH61427, P30MH075673)
- National Institute on Drug Abuse (DA61427)
- National Institute of Neurological Disorders and Stroke (U54NS056883, S11NS046278, U54NS 43011, S11NS46278, NS56883, U54NS043011)
- National Center for Research Resources (1U54RR026139-01A1, U54-RR026139)
- National Institute on Minority Health and Health Disparities (U54MD007587)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- HIV-associated neurocognitive disorders, cognitive decline, ceramide, cholesterol metabolism, sphingolipids, esterified cholesterol, highly active antiretroviral therapy, lipid storage disease, prognostic factors
- MeSH terms
- Adult, Ceramides, Cholesterol, Female, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Sphingolipids, Biomarkers, AIDS Dementia Complex, HIV Infections, Antiretroviral Therapy, Highly Active, Lipid Metabolism Disorders
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