The KEEPS-Cognitive and Affective Study: Baseline Associations between Vascular Risk Factors and Cognition

Article type: Research Article

Authors: Wharton, Whitney^{a; b; *} | Gleason, Carey E.^{c; d; e} | Dowling, N. Maritza^{c; e; f} | Carlsson, Cynthia M.^{c; d; e} | Brinton, Eliot A.^g | Santoro, M. Nanette^h | Neal-Perry, Genevieveⁱ | Taylor, Hugh^j | Naftolin, Frederick^k | Lobo, Rogerio A.^l | Merriam, George^m | Manson, JoAnn E.ⁿ | Cedars, Marcelle I.^o | Miller, Virginia M.^p | Black, Dennis M.^q | Budoff, Matthew^r | Hodis, Howard N.^s | Harman, S. Mitchell^t | Asthana, Sanjay^{c; d; e}

Affiliations: [a] Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA | [b] Emory Alzheimer's Disease Research Center, (ADRC) Atlanta, GA, USA | [c] Department of Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA | [d] Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA | [e] Wisconsin Alzheimer's Disease Research Center, (ADRC) Madison, WI, USA | [f] University of Wisconsin, Department of Biostatistics and Medical Informatics, Madison, WI, USA | [g] Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA | [h] Obstetrics & Gynecology, University of Colorado School of Medicine, Aurora, CO, USA | [i] Obstetrics & Gynecology, Albert Einstein College of Medicine, Bronx, NY, USA | [j] Obstetrics & Gynecology, Yale University School of Medicine, New Haven, CT, USA | [k] Obstetrics & Gynecology, New York University, New York, NY, USA | [l] Obstetrics & Gynecology, Columbia University School of Medicine, New York, NY, USA | [m] VA Puget Sound Health Care System and Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, USA | [n] Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA | [o] Obstetrics & Gynecology, University of California at San Francisco, San Francisco, CA, USA | [p] Surgery & Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA | [q] Epidemiology & Biostatistics, University of California at San Francisco, San Francisco, CA, USA | [r] Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA | [s] Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, USA | [t] Kronos Longevity Research Institute and Phoenix VA Medical Center, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Whitney Wharton, Ph.D., Emory University, Department of Neurology, Emory Alzheimer's Disease Research Center, Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, GA 30329, USA. Tel.: +1 404 728 6918; E-mail: [email protected].

Abstract: Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42–59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

Keywords: Attention, blood pressure, clinical trial, cognition, estradiol, estrogen, hormone therapy, memory, vascular risk

DOI: 10.3233/JAD-130245

Journal: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 331-341, 2014