PMID- 35308084 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240214 IS - 2666-3546 (Electronic) IS - 2666-3546 (Linking) VI - 21 DP - 2022 May TI - Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years. PG - 100437 LID - 10.1016/j.bbih.2022.100437 [doi] LID - 100437 AB - BACKGROUND: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years. METHODS: PWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor - type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Abeta)-42, soluble amyloid precursor protein-alpha (sAPPalpha)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline. RESULTS: Participants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/muL (19,205), current CD4 568/muL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPalpha). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r ​= ​-0.168, p ​= ​0.0205 and r ​= ​-0.156, p ​= ​0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r ​= ​-0.154, p ​= ​0.0332), while IL-6 did not (r ​= ​-0.109, p ​= ​0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r ​= ​-0.1734, p ​= ​0.0006). Together BDI-II (p ​= ​0.0290), F1 (p ​= ​0.0484) and F3 (p ​= ​0.0309) contributed independently to NC decline (p ​= ​0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression. CONCLUSIONS: PWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation. CI - (c) 2022 The Authors. FAU - Ellis, Ronald J AU - Ellis RJ AD - University of California San Diego, San Diego, CA, United States. FAU - Heaton, Robert K AU - Heaton RK AD - University of California San Diego, San Diego, CA, United States. FAU - Tang, Bin AU - Tang B AD - University of California San Diego, San Diego, CA, United States. FAU - Collier, A C AU - Collier AC AD - University of Washington, Seattle, WA, United States. FAU - Marra, Christina M AU - Marra CM AD - University of Washington, Seattle, WA, United States. FAU - Gelman, Benjamin B AU - Gelman BB AD - University of Texas at Galveston, Galveston, TX, United States. FAU - Morgello, S AU - Morgello S AD - Icahn School of Medicine at Mount Sinai, New York, NY, United States. FAU - Clifford, David B AU - Clifford DB AD - Washington University, St Louis, MO, United States. FAU - Sacktor, N AU - Sacktor N AD - Johns-Hopkins University, Baltimore, MD, United States. FAU - Cookson, D AU - Cookson D AD - University of California San Diego, San Diego, CA, United States. FAU - Letendre, Scott AU - Letendre S AD - University of California San Diego, San Diego, CA, United States. LA - eng GR - HHSN271201000030C/MH/NIMH NIH HHS/United States GR - HHSN271201000036C/MH/NIMH NIH HHS/United States GR - UM1 AI069481/AI/NIAID NIH HHS/United States GR - P30 MH062512/MH/NIMH NIH HHS/United States GR - N01 MH022005/MH/NIMH NIH HHS/United States GR - R01 MH107345/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20220310 PL - United States TA - Brain Behav Immun Health JT - Brain, behavior, & immunity - health JID - 101759062 PMC - PMC8928134 COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/03/22 06:00 MHDA- 2022/03/22 06:01 PMCR- 2022/03/10 CRDT- 2022/03/21 08:34 PHST- 2021/12/08 00:00 [received] PHST- 2022/02/09 00:00 [revised] PHST- 2022/02/26 00:00 [accepted] PHST- 2022/03/22 06:00 [pubmed] PHST- 2022/03/22 06:01 [medline] PHST- 2022/03/21 08:34 [entrez] PHST- 2022/03/10 00:00 [pmc-release] AID - S2666-3546(22)00027-8 [pii] AID - 100437 [pii] AID - 10.1016/j.bbih.2022.100437 [doi] PST - epublish SO - Brain Behav Immun Health. 2022 Mar 10;21:100437. doi: 10.1016/j.bbih.2022.100437. eCollection 2022 May.