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.

Objective

We evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and human immunodeficiency virus (HIV) infection with cognition. We hypothesized that HIV-infected perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition.

Methods

This cross-sectional study included 708 HIV-infected and 278 HIV-uninfected premenopausal, perimenopausal, or postmenopausal women (64% African American; median age, 44 y) from the Women's Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms.

Results

In multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (P's < 0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (P's < 0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (P's < 0.05). Vasomotor symptoms were associated with worse attention (P < 0.05). HIV and anxiety symptoms interacted to influence verbal learning (P's < 0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only.

Conclusions

Vasomotor, depressive, and anxiety symptoms, but not menopausal stage, are associated with worse cognitive performance in both HIV-infected and HIV-uninfected women, although elevated anxiety symptoms are more associated with verbal learning deficits in HIV-infected women. Because cognitive problems can interfere with everyday functioning, including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women.