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Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial

HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain–derive...

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Autores principales: Thela, Lindokuhle, Decloedt, Eric, Zetterberg, Henrik, Gisslén, Magnus, Lesosky, Maia, Gleich, Melanie, Koutsilieri, Eleni, Scheller, Carsten, Hye, Abdul, Joska, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185609/
https://www.ncbi.nlm.nih.gov/pubmed/36790601
http://dx.doi.org/10.1007/s13365-023-01116-4
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author Thela, Lindokuhle
Decloedt, Eric
Zetterberg, Henrik
Gisslén, Magnus
Lesosky, Maia
Gleich, Melanie
Koutsilieri, Eleni
Scheller, Carsten
Hye, Abdul
Joska, John
author_facet Thela, Lindokuhle
Decloedt, Eric
Zetterberg, Henrik
Gisslén, Magnus
Lesosky, Maia
Gleich, Melanie
Koutsilieri, Eleni
Scheller, Carsten
Hye, Abdul
Joska, John
author_sort Thela, Lindokuhle
collection PubMed
description HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain–derived neurotrophic factors (BDNF). Lithium is also an inhibitor of glycogen synthase kinase-3 beta (GSK-3-β). We analyzed biomarkers obtained from participants in a randomized placebo-controlled trial of lithium in ART-treated individuals with moderate or severe HAND. We assayed markers at baseline and 24 weeks across several pathways hypothesized to be affected by HIV, inflammation, or degeneration. Investigated biomarkers included dopamine, BDNF, neurofilament light chain, and CD8 + lymphocyte activation (CD38 + HLADR +). Alzheimer’s Disease (AD) biomarkers included soluble amyloid precursor protein alpha and beta (sAPPα/β), Aβ38, 40, 42, and ten other biomarkers validated as predictors of mild cognitive impairment and progression in previous studies. These include apolipoprotein C3, pre-albumin, α1-acid glycoprotein, α1-antitrypsin, PEDF, CC4, ICAM-1, RANTES, clusterin, and cystatin c. We recruited 61 participants (placebo = 31; lithium = 30). The age baseline mean was 40 (± 8.35) years and the median CD4 + T-cell count was 498 (IQR: 389–651) cells/μL. Biomarker concentrations between groups did not differ at baseline. However, both groups’ blood dopamine levels decreased significantly after 24 weeks (adj. p < 002). No other marker was significantly different between groups, and we concluded that lithium did not confer neuroprotection following 24 weeks of treatment. However, the study was limited in duration and sample size. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13365-023-01116-4.
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spelling pubmed-101856092023-05-17 Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial Thela, Lindokuhle Decloedt, Eric Zetterberg, Henrik Gisslén, Magnus Lesosky, Maia Gleich, Melanie Koutsilieri, Eleni Scheller, Carsten Hye, Abdul Joska, John J Neurovirol Article HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain–derived neurotrophic factors (BDNF). Lithium is also an inhibitor of glycogen synthase kinase-3 beta (GSK-3-β). We analyzed biomarkers obtained from participants in a randomized placebo-controlled trial of lithium in ART-treated individuals with moderate or severe HAND. We assayed markers at baseline and 24 weeks across several pathways hypothesized to be affected by HIV, inflammation, or degeneration. Investigated biomarkers included dopamine, BDNF, neurofilament light chain, and CD8 + lymphocyte activation (CD38 + HLADR +). Alzheimer’s Disease (AD) biomarkers included soluble amyloid precursor protein alpha and beta (sAPPα/β), Aβ38, 40, 42, and ten other biomarkers validated as predictors of mild cognitive impairment and progression in previous studies. These include apolipoprotein C3, pre-albumin, α1-acid glycoprotein, α1-antitrypsin, PEDF, CC4, ICAM-1, RANTES, clusterin, and cystatin c. We recruited 61 participants (placebo = 31; lithium = 30). The age baseline mean was 40 (± 8.35) years and the median CD4 + T-cell count was 498 (IQR: 389–651) cells/μL. Biomarker concentrations between groups did not differ at baseline. However, both groups’ blood dopamine levels decreased significantly after 24 weeks (adj. p < 002). No other marker was significantly different between groups, and we concluded that lithium did not confer neuroprotection following 24 weeks of treatment. However, the study was limited in duration and sample size. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13365-023-01116-4. Springer International Publishing 2023-02-15 2023 /pmc/articles/PMC10185609/ /pubmed/36790601 http://dx.doi.org/10.1007/s13365-023-01116-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Thela, Lindokuhle
Decloedt, Eric
Zetterberg, Henrik
Gisslén, Magnus
Lesosky, Maia
Gleich, Melanie
Koutsilieri, Eleni
Scheller, Carsten
Hye, Abdul
Joska, John
Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title_full Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title_fullStr Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title_full_unstemmed Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title_short Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
title_sort blood and cerebrospinal fluid biomarker changes in patients with hiv-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185609/
https://www.ncbi.nlm.nih.gov/pubmed/36790601
http://dx.doi.org/10.1007/s13365-023-01116-4
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