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Investigation of menopausal stage and symptoms on cognition in human immunodeficiency virus–infected women

Rubin, Leah H. PhD1; Sundermann, Erin E. PhD1; Cook, Judith A. PhD1; Martin, Eileen M. PhD2; Golub, Elizabeth T. PhD, MPH3; Weber, Kathleen M. RN, BSN4; Cohen, Mardge H. MD4,5; Crystal, Howard MD6; Cederbaum, Julie A. PhD7; Anastos, Kathyrn MD8; Young, Mary MD9; Greenblatt, Ruth M. MD10; Maki, Pauline M. PhD1,11

doi: 10.1097/GME.0000000000000203
Original Articles

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.

From the 1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL; 2Department of Psychiatry, Rush University, Chicago, IL; 3Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD; 4The Core Center, Cook County Health and Hospital System and Hektoen Institute of Medicine, Chicago, IL; 5Department of Medicine, Stroger Hospital and Rush University, Chicago, IL; 6Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY; 7School of Social Work, University of Southern California, Los Angeles, CA; 8Department of Medicine and Epidemiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; 9Georgetown University School of Medicine, Washington, DC; 10Departments of Clinical Pharmacy, Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, CA; and 11Department of Psychology, University of Illinois at Chicago, Chicago, IL.

Received October 22, 2013; revised and accepted December 4, 2013.

The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Preliminary data were presented at The North American Menopause Society, San Diego, CA, October 1 to 3, 2009 (poster), and at the Ninth Annual Interdisciplinary Women’s Health Research Symposium, Washington, DC, November 15, 2012 (invited talk).

Funding/support: L.H.R. was supported by the National Institute of Mental Health (grant 1K01MH098798-01), the National Institute of Child Health and Human Development (grant K12HD055892), and the National Institutes of Health Office of Research on Women’s Health. Data in this manuscript were collected by the Women’s Interagency HIV Study Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The Women’s Interagency HIV Study was funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study was cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding was also provided by the National Center for Research Resources (University of California San Francisco–Clinical and Translational Science Institute grant UL1 RR024131).

Financial disclosure/conflicts of interest: P.M.M. served as a consultant for Depomed pharmaceuticals; K.A. served as a consultant for Bristol Meyers Squibb.

Address correspondence to: Leah H. Rubin, PhD, Department of Psychiatry, University of Illinois at Chicago, MC 913, 912 South Wood Street, Chicago, IL 60612. E-mail:

© 2014 by The North American Menopause Society.