The KEEPS-cognitive and affective study: Baseline associations between vascular risk factors and cognition

Whitney Wharton, Carey E. Gleason, N. Maritza Dowling, Cynthia M. Carlsson, Eliot A. Brinton, M. Nanette Santoro, Genevieve Neal-Perry, Hugh Taylor, Frederick Naftolin, Rogerio A. Lobo, George Merriam, Joann E. Manson, Marcelle I. Cedars, Virginia M. Miller, Dennis M. Black, Matthew Budoff, Howard N. Hodis, S. Mitchell Harman, Sanjay Asthana

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)331-341
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2014


  • Attention
  • blood pressure
  • clinical trial
  • cognition
  • estradiol
  • estrogen
  • hormone therapy
  • memory
  • vascular risk

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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