Project 2. Effects of Menopausal Hormone Therapy on Imaging Markers of Cognitive Health

Principal investigator: Kejal Kantarci, M.D., co-investigators: Val Lowe, M.D., and Julie Fields, Ph.D., L.P.

The long-term goal of this research is to establish noninvasive imaging markers for measuring the effectiveness of treatments to prevent dementia. Specifically, this project will investigate the neuroprotective effects of estrogen treatment on surrogate imaging markers of cognitive health and cognitive performance in women who were treated with estrogens vs. placebo during early menopause, which is considered the critical stage or "window of opportunity" for estrogen treatment.

These experiments will build off the Kronos Early Estrogen Study (KEEPS), which is a nationwide, multicenter, randomized blinded study of estrogen treatment in newly menopausal women. Mayo Clinic enrolled 105 women who underwent brain MRI studies and cognitive testing at baseline before they were randomized to treatment. We are proposing to follow KEEPS participants with imaging and cognitive studies seven years after randomization.

Four imaging markers will be employed:

  • Volume of WMH by MRI as a surrogate for ischemic white matter disease
  • PiB (Pittsburgh compound B) retention on PET as a surrogate for beta-amyloid pathology of Alzheimer's disease
  • Ventricular volume change on MRI as a surrogate for neuronal degeneration
  • Regional atrophy rates using tensor-based morphometry by MRI

Each of these surrogates will be evaluated in association with cognitive function. Results from this study will stand on their own to address the controversy of whether MHT administered to postmenopausal women within the “window of opportunity” affect brain-imaging surrogates of cognitive health. Results will clarify the question posed in the overarching theme of the SCOR of how the female sex-specific condition of menopause and menopausal hormone therapy impact cognition. Because women identified in this project will undergo testing of cerebrovascular function and platelet/microvesicle analysis, it will be possible to provide insight into mechanisms for ischemic or degenerative changes in the brain that result from a history of natural menopause or from menopausal hormone therapy.