Association between central adiposity and cognitive domain function in recently postmenopausal women: an analysis from the KEEPS-Cog substudy of the Kronos Early Estrogen Preventive Study

Taryn T. James, University of Wisconsin-Madison, Madison, WI.
N Maritza Dowling, George Washington University, Washington, DC.
Carola Ferrer Simó, University of Wisconsin-Madison, Madison, WI.
Hector Salazar, University of Pittsburgh, School of Nursing, Pittsburgh, PA.
Carol A. Van Hulle, University of Wisconsin-Madison, Madison, WI.
Gilda Ennis, University of Wisconsin-Madison, Madison, WI.
Adrienne L. Johnson, University of Wisconsin-Madison, Madison, WI.
Mary F. Wyman, University of Wisconsin-Madison, Madison, WI.
Lauren W. McLester-Davis, University of Wisconsin-Madison, Madison, WI.
Diane C. Gooding, University of Wisconsin-Madison, Madison, WI.
Barbara Fischer, University of Wisconsin-Madison, Madison, WI.
Shenikqua Bouges, University of Wisconsin-Madison, Madison, WI.
Emre Umucu, University of Texas at El Paso, El Paso, TX.
Firat Kara, Mayo Clinic, Rochester, MN.
Juliana M. Kling, Mayo Clinic, Scottsdale, AZ.
JoAnn E. Manson, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Eliot A. Brinton, Utah Lipid Center, Salt Lake City, UT.
Marcelle I. Cedars, University of California, San Francisco, CA.
Rogerio A. Lobo, Columbia University, New York City, NY.
Genevieve Neal-Perry, University of North Carolina-Chapel Hill, Chapel Hill, NC.
Nanette F. Santoro, University of Colorado School of Medicine, Aurora, CO.
Frederick Naftolin, e-Bio Corporation, New York, NY.
Sherman M. Harman, Phoenix VA Health Care System, Phoenix, AZ.
Lubna Pal, Yale University, New Haven, CT.
Virginia M. Miller, University of Texas at El Paso, El Paso, TX.
Kejal Kantarci, University of Texas at El Paso, El Paso, TX.
Carey E. Gleason, University of Wisconsin-Madison, Madison, WI.

Document Type

Journal Article

Publication Date

11-4-2025

Journal

Menopause (New York, N.Y.)

DOI

10.1097/GME.0000000000002666

Keywords

Central adiposity; Estrogens; Menopausal hormone therapy; Metabolic syndrome diseases; Waist-to-hip ratio

Abstract

OBJECTIVE: To determine associations between central adiposity, cognitive function, and randomized menopausal hormone therapy (MHT) in a reanalysis of the Kronos Early Estrogen Prevention Study-Cognitive and Affective (KEEPS-Cog) sub-study participants. METHODS: KEEPS randomized 727 women (ages 42-58) who were <36 months postnatural menopause to oral conjugated equine estrogens (o-CEE), transdermal 17-β-estradiol (t-E2), or placebo for 48 months. Participants with diabetes, body mass index >35 kg/m2, coronary artery calcium score >50 Agatston Units, and other cardiometabolic disease risk indicators were excluded from enrollment. In the ancillary KEEPS-Cog study, cognitive tests were completed at baseline, 18-, 36-, and 48-month post-randomization. In these analyses, cognitive variables were summarized as four cognitive domain-specific factor scores: verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. Waist-hip-ratio (WHR), an indicator of central adiposity, was measured at screening (baseline) and modeled as a covariate in linear latent growth models assessing associations of MHT with cognitive functions at baseline and over time. RESULTS: Higher baseline WHR was associated with poorer performance on all domain-specific cognitive outcomes at baseline and with changes in visual attention and executive function across time. Models including interaction effects were not significant for either o-CEE x WHR or t-E2 x WHR. CONCLUSION: Central adiposity is a risk factor for domain-specific cognitive decline, and thus, cognitive health effects should be investigated in early postmenopausal women, even in women with low cardiovascular risk statuses.

Department

Nursing Faculty Publications

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