Women’s Brain Health: Midlife Ovarian Removal Affects Associative Memory

Abstract

Women with early bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) have greater Alzheimer’s disease (AD) risk than women in spontaneous/natural menopause (SM), but early biomarkers of this risk are not well-characterized. Considering associative memory deficits may presage preclinical AD, we wondered if one of the earliest changes might be in associative memory and whether younger women with BSO had changes similar to those observed in SM. Women with BSO (with and without 17β-estradiol replacement therapy (ERT)), their age-matched premenopausal controls (AMC), and older women in SM completed a functional magnetic resonance imaging face-name associative memory task shown to predict early AD. Brain activation during encoding was compared between groups: AMC (n=25), BSO no ERT (BSO; n=15), BSO+ERT (n=16), and SM without hormone therapy (n=16). Region-of-interest analyses revealed AMC did not contribute to functional group differences. BSO+ERT had higher hippocampal activation than BSO and SM. This hippocampal activation correlated positively with urinary metabolite levels of 17β-estradiol. Multivariate partial least squares analyses showed BSO+ERT had a different network-level activation pattern than BSO and SM. Thus, despite being approximately 10 years younger, women with BSO without ERT had similar brain function to those with SM, suggesting early 17β-estradiol loss may lead to an altered functional brain phenotype which could influence late-life AD risk, making face-name encoding a potential biomarker for midlife women with increased AD risk. Despite similarities in activation, BSO and SM groups showed opposite within-hippocampus connectivity, suggesting menopause type is an important consideration when assessing brain function.

Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia

“…That similar right-lateralized areas of higher GM volume were not observed for either the BSO or the BRCA-preBSO groups suggests that postsurgical ERT may play a role in this plasticity. 61 Additionally, areas of higher GM volume were observed in right subcortical structures, including thalamus, putamen, and caudate, as well as extensively in bilateral cerebellum. Postmortem ER mapping in humans has indicated that structures like the putamen and caudate do not have high densities of ERs, suggesting that even without obvious structural changes, the brain may be recruiting those areas less affected by the sudden postsurgical E 2 loss in an effort to preserve function.…”

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later‐life

“…Premenopausal bilateral oophorectomy (PBO) causes abrupt endocrine dysfunction (e.g., loss of estrogen, progesterone, testosterone, and an increase in gonadotropins). Studies suggest that females with PBO are at an increased risk of cognitive impairment and dementia, 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 but few neuroimaging studies have been conducted to clarify the underlying pathogenesis. One small study reported PBO was associated with smaller amygdala volume, thinner parahippocampal‐entorhinal cortex, and lower entorhinal white matter fractional anisotropy (FA) compared to referent females.…”