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. 2021 Mar:93:111-118.
doi: 10.1016/j.bbi.2020.12.021. Epub 2020 Dec 24.

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda

Alyssa C Vecchio  1 , Dionna W Williams  2 , Yanxun Xu  3 , Danyang Yu  4 , Deanna Saylor  5 , Sarah Lofgren  6 , Riley O'Toole  7 , David R Boulware  6 , Noeline Nakasujja  8 , Gertrude Nakigozi  9 , Alice Kisakye  9 , James Batte  9 , Richard Mayanja  9 , Aggrey Anok  9 , Steven J Reynolds  10 , Thomas C Quinn  10 , Ronald H Gray  11 , Maria J Wawer  11 , Ned Sacktor  5 , Leah H Rubin  12
Affiliations

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda

Alyssa C Vecchio et al. Brain Behav Immun. 2021 Mar.

Abstract

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.

Keywords: Cognition; Global health; HIV; Inflammation; Sex.

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Conflict of interest statement

Conflicts of interest

All coauthors have nothing to disclose.

Figures

Figure 1.
Figure 1.
Log CSF inflammatory levels in the overall sample and by sex. MWH=men with HIV; WWH=women with HIV.
Figure 2.
Figure 2.
Neuropsychological performance in the overall sample and by sex. MWH=men with HIV; WWH=women with HIV. ***P<0.001; **P<0.01; *P<0.05; + P=0.05
Figure 3.
Figure 3.
Significant associations (boxes with standardized beta coefficients) between CSF inflammatory markers and cognitive performance in the overall sample. Coeff=standardized beta coefficient. GPEG=Grooved Pegboard; SDMT=Symbol Digit Modalities Test; DSPAN=Digit Span; AVLT=Auditory Verbal Learning Test.
Figure 4.
Figure 4.
Significant associations (boxes with standardized beta coefficients) between CSF inflammatory markers and cognitive performance by sex. Coeff=standardized beta coefficient. GPEG=Grooved Pegboard; SDMT=Symbol Digit Modalities Test; DSPAN=Digit Span; AVLT=Auditory Verbal Learning Test.
See this image and copyright information in PMC

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