Bilateral Oophorectomy on Imaging Biomarkers of Alzheimer's and Cerebrovascular Diseases

Hypothesis

Investigators in the Mayo Clinic SCORE on Sex Differences are testing the hypothesis that imaging biomarkers of Alzheimer's disease and cerebrovascular disease pathophysiology will differ in women who had both ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy, or BSO) before reaching menopause, compared with an age-matched referent cohort of women who did not undergo premenopausal BSO. Further, the team hypothesizes that this difference will be modulated by the APOE genotype.

This study provides a unique opportunity to clarify how abrupt ovarian hormonal disruption affects the long-term risk of cognitive decline and dementia through imaging biomarkers of early pathology. For women considering BSO for cancer prophylaxis, the findings will provide critical insights to help guide their health care decisions.

Women participating in the study ranged in age from 66 to 85 years old; the median age was 66.

Background

Women who undergo BSO before the onset of menopause have an accelerated accumulation of multimorbidity, with an increased risk of aging-related neurological diseases, including dementia. The most common pathologies that contribute to cognitive impairment and dementia in women are Alzheimer's disease and cerebrovascular disease.

Determining how premenopausal BSO affects the risk of dementia would require decades of follow-up; alternatively, noninvasive imaging biomarkers can potentially assess the effects of an abrupt loss of ovarian hormones on the risk of Alzheimer's and cerebrovascular diseases in a shorter time frame. Furthermore, imaging biomarkers may provide insight into the underlying causes of cognitive impairment and dementia associated with premenopausal BSO.

Project aims

The specific goals of the SCORE's project on how BSO affects imaging biomarkers of Alzheimer's disease and cerebrovascular disease are to:

  • Quantify and compare Alzheimer's-related β-amyloid and tau pathology and Alzheimer's-related neurodegeneration in women with a history of premenopausal BSO with age-matched referent women
  • Quantify and compare MRI findings associated with cerebrovascular disease in women with a history of premenopausal BSO with age-matched referent women
  • Determine whether the APOE genotype modifies the above associations
  • Determine the association of neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease with cognitive function in women with a history of premenopausal BSO, compared with age-matched referent women

Project leader