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Variability in C-reactive protein is associated with cognitive impairment in women living with and without HIV: a
Leah H Rubin1,2, Lorie Benning3, Sheila M Keating4
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA. lrubin1@jhmi.edu.
Insights
Cognitive impairment (CI) in women with and without HIV may be predicted by changes in inflammatory markers over time. Greater variability in C-reactive protein (CRP) specifically predicted cognitive decline in both groups.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Women's Health
Background:
- Cognitive impairment (CI) persists in HIV-infected (HIV+) individuals despite effective antiretroviral therapy.
- Inflammatory processes driven by monocytes and macrophages are implicated in HIV-associated CI, primarily in male cohorts.
- Sex differences in immune function necessitate investigation into inflammatory markers and CI in women.
Purpose of the Study:
- To investigate the predictive value of mean and intra-individual variability of peripheral inflammatory markers for cognitive impairment (CI) in HIV-positive (HIV+) and HIV-negative women.
- To explore sex-specific differences in the relationship between inflammatory markers and CI.
Main Methods:
- Analysis of 13 peripheral immune markers from stored biospecimens at three time points in 72 HIV+ and 58 HIV- women.
- Neuropsychological testing to determine cognitive impairment (CI) status.
- Propensity score matching was used to control for confounding variables.
Main Results:
- HIV+ women exhibited alterations in 8 immune markers compared to HIV- women.
- Lower mean soluble tumor necrosis factor receptor I (sTNFRI) and higher mean interleukin-6 (IL-6) levels predicted CI across both groups.
- Greater intra-individual variability in C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) were the strongest predictors of CI.
- Specifically, CRP variability predicted lower executive function, attention/working memory, and psychomotor speed in HIV+ women, and learning in HIV- women.
Conclusions:
- Intra-individual variability in C-reactive protein (CRP) levels over time is a significant predictor of cognitive impairment (CI).
- This finding holds true for both HIV-positive and HIV-negative women, suggesting a broader role for inflammatory variability in cognitive health.
- CRP variability may serve as a valuable biomarker for tracking cognitive changes, particularly in diverse populations of midlife women.
Abstract:
Despite the availability of effective antiretroviral therapies, cognitive impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence from primarily cross-sectional studies, in predominantly male samples, implicates monocyte- and macrophage-driven inflammatory processes linked to HIV-associated CI. Thus, peripheral systemic inflammatory markers may be clinically useful biomarkers in tracking HIV-associated CI. Given sex differences in immune function, we focused here on whether mean and intra-individual variability in inflammatory marker-predicted CI in HIV+ and HIV- women. Seventy-two HIV+ (36 with CI) and 58 HIV- (29 with CI) propensity-matched women participating in the Women's Interagency HIV Study completed a neuropsychological battery once between 2009 and 2011, and performance was used to determine CI status. Analysis of 13 peripheral immune markers was conducted on stored biospecimens at three time points (7 and 3.5 years before neuropsychological data collection and concurrent with data collection). HIV+ women showed alterations in 8 immune markers compared to HIV- women. The strongest predictors of CI across HIV+ and HIV- women were lower mean soluble tumor necrosis factor receptor I (sTNFRI) levels, higher mean interleukin (IL)-6 levels, and greater variability in C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 (p values < 0.05). Stratified by HIV, the only significant predictor of CI was greater variability in CRP for both HIV+ and HIV- women (p values < 0.05). This variability predicted lower executive function, attention/working memory, and psychomotor speed in HIV+ but only learning in HIV- women (p values < 0.05). Intra-individual variability in CRP levels over time may be a good predictor of CI in predominately minority low-socioeconomic status midlife women.
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