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
Year: 2025
Type: article
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/m 2 , 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.
Authors: Taryn T. James, N. Maritza Dowling, Carola Ferrer Simó, Hector Salazar, Carol A. Van Hulle, Gilda Ennis, Adrienne L. Johnson, Mary F. Wyman, Lauren W. Y. McLester-Davis, Diane C. Gooding, Barbara Fischer, Shenikqua Bouges, Emre Umucu, Firat Kara, Juliana M. Kling, JoAnn E. Manson, Eliot A. Brinton, Marcelle I. Cedars, Rogerio A. Lobo, Genevieve Neal-Perry, Nanette F. Santoro, Frederick Naftolin, Sherman M. Harman, Lubna Pal, Virginia M. Miller, Kejal Kantarci, Carey E. Gleason
Institutions: University of Wisconsin–Madison, George Washington University, University of Pittsburgh, William S. Middleton Memorial Veterans Hospital, The University of Texas at El Paso, Mayo Clinic, Mayo Clinic in Arizona, Brigham and Women's Hospital, Harvard University, University of California, San Francisco, Columbia University, University of North Carolina at Chapel Hill, University of Colorado Anschutz, University of Colorado Denver, Phoenix VA Health Care System, Yale University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Clinical and Translational Science Institute, Estrogen, Platelets, and Artherosclerosis, Research Infrastructure for the study of Alzheimer's Disease and Alzheimer's Disease-related dementias in older Asian Americans, Clinical and Translational Science Award (UL1), Clinical and Translational Science Award-K12, KEEPS Cognitive and Affective Study, Prevention of Alzheimer's disease in women: risks and benefits of hormone therapy, Yale University Clinical and Translational Science Award Program, Clinical and Translational Science Award-T32 (TL1), Mayo Clinic Center for Translational Science Activities, Arterial Stiffness, Cognition, and Equol (ACE), ADRD Prevention Messaging to Increase Smoking Cessation Attempts in Older Adult Smokers, Premenopausal bilateral oophorectomy and biomarkers of Alzheimer’s and cerebrovascular diseases, Colorado Nutrition Obesity Research Center
OpenAlex ID: W4415879769