The Effect of Bilateral Salpingo-Oophorectomy on Cognition in Women Prior to Natural Menopause

In this dissertation, I examined the effects of 17β-estradiol on cognitive functioning in middle-aged women, using a model of ovarian removal. Women with a BRCA1/2 mutation who have undergone bilateral salpingo-oophorectomy (BSO) for cancer prevention prior to natural menopause were enrolled in an accelerated longitudinal study designed to examine cognition up to 10 years post-surgically. The literature has found that women who have experienced an iatrogenic loss of estrogens following BSO are at increased risk of cognitive decline and dementia. The objective of my dissertation was to characterize two periods that have not been previously studied: up to 10-years post surgically and the timeframe leading up to dementia. I present here findings from the first year of cognitive testing in an accelerated longitudinal study, and retrospective analyses using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. I examined the effects of oophorectomy on verbal memory (Chapter 3), and executive functioning (Chapter 4) based on localization of estrogen receptors in the hippocampus and frontal cortex. In Chapter 5, I explored the interaction between a BRCA mutation and BSO on spatial memory. In Chapter 6, I examined if elderly women (aged >55 baseline) with a history of oophorectomy and mild cognitive impairment were at greater risk of conversion to Alzheimer’s disease using the ADNI database to understand the trajectory leading up to dementia. Overall, results indicate that performance of women with BSO were similar to controls except for a measure of verbal, episodic memory. In addition, a number of factors within the BSO group modulate cognitive functioning. This included levels of endogenous estrogens, the age at surgery, time since surgery, hormone therapy and education attainment. Results suggest that there are protective factors that modulate the risk of cognitive decline post-BSO, and more generally, underscore the complexity of the relationship between estrogens and cognition in middle-aged women.Ph.D.2020-07-10 00:00:0