Premenopausal bilateral oophorectomy and biomarkers of Alzheimer’s and cerebrovascular diseases - PROJECT SUMMARY / ABSTRACT The social and economic implications of dementia is greatest in women because of their longer life expectancy and resulting elevated risk for dementia compared to men, and this risk of dementia in women may be, in part, modulated by ovarian hormones. Although premenopausal bilateral oophorectomy (PBO) is associated with a reduced risk of ovarian and breast cancer, it is also associated with an increased risk of dementia and other neurological diseases later in life. It is estimated that one in ten U.S. women have undergone abrupt endocrine disruption by having their ovaries removed before reaching natural menopause and this rate is even higher in African American/Black (AA) women. For the large number of women who underwent prophylactic PBO over the past decade, it is critical that the pathologic mechanisms by which PBO influences the risk of dementia should be determined in a rigorous manner for preventive approaches. The most common pathologies that contribute to cognitive impairment and dementia are Alzheimer's disease (AD) and cerebrovascular disease. Our goal is to understand the effects of abrupt disruption of ovarian hormones before the onset of menopause on imaging biomarkers of AD and cerebrovascular disease pathophysiology later in life. We will enroll 150 women who underwent PBO and 150 women who did not undergo PBO drawn from a well-characterized and established population-based cohort. Because our current cohort is predominantly White in Mayo Clinic Rochester, we plan to enrich this cohort with a new AA cohort from Mayo Clinic Florida to reach a sample of 400 women (200 with and 200 without PBO). We hypothesize that imaging biomarkers of AD and cerebrovascular disease, and cognitive function will be abnormal both cross-sectionally and longitudinally in women who underwent PBO compared to referent women who did not undergo PBO, and that this difference will be modified by race (AA versus White), age at PBO, and APOE ε4. Findings from the proposed project have implications both for research and for clinical practice. Findings will contribute to clarifying the mechanisms underlying the development of dementia in women who underwent PBO. In addition, they hold the potential to alter the clinical practice paradigms related to PBO for non-malignant indications and outside of the setting of high genetic risk of ovarian cancer. For the one in ten women currently facing the decision to undergo PBO, determining the late life effects of PBO on the brain is critical for maintaining cognitive health in the long-term.
