Cognitive and brain health in women with early bilateral salpingo-oophorectomy: Implications for risk, resilience, and subjective cognitive decline

Abstract

Introduction: Early life bilateral salpingo-oophorectomy (BSO) leads to immediate estradiol loss and increased risk of late-life Alzheimer's disease (AD). We investigated risk and resilience (RandR) on the average of 5 years post BSO and their possible impact on subjective cognitive decline (SCD), and brain structure.

Methods: A cohort in Canada (n = 333) included women with and without BSO of whom some reported SCD. We used multiple factor analysis, logistic regression, and magnetic resonance imaging to assess RandR, odds of SCD, and differences in gray matter volume (GMV).

Results: BSO was a risk for worse neuropsychological performance, a 2-fold increase in the odds of SCD, and decreases in GMV in regions sensitive to estradiol, and important for mood, memory, and language. However, estradiol therapy (ET_BSO), and verbal IQ mitigated this risk.

Discussion: Risk of SCD exists for younger women with BSO, which affects GMV. Importantly, ET_BSO and verbal IQ may shift that risk.

Highlights: Oophorectomy in early middle age may be a risk for subjective cognitive decline. Oophorectomy is associated with less gray matter volume in the prefrontal cortex. Estradiol therapy and verbal IQ might be resilience factors mitigating such risk.

Keywords: early life bilateral salpingo‐oophorectomy; estradiol; estradiol therapy; risk and resilience; subjective cognitive decline; verbal IQ.

FIGURE 1

MFA correlation pattern for AMC, BRCA‐C, and BSO. A, Correlation circle showing the topographical influence in the arrangement of the variables on the graph along the abscissa (D1) and the ordinate (D2). Positively correlated variables are grouped together, whereas negative ones are positioned on opposite sides of the plot origin (opposed quadrants). For D1, the variables that were positively associated are grouped together on the right side of the plot, and the variables that were negatively associated with these are on the left side. D2 shows a similar separation with the variables positively associated at the top of the plot and the variables negatively associated at the bottom of the plot. Note that E1G is not grouped together with the other set of variables. The most contributing variables are on a gradient, with orange representing the most contribution to the pattern. The bar plots for (B) and (C) represent the moderate and strong correlations of the variables that contributed the most. Variables in the top of the bar plots show positive correlations, and variables on the bottom show negative correlations. Variables that contribute the most to D1 and D2 (either positive or negative correlations) are the most important in explaining the variability in the data set. APOE, apolipoprotein E gene; BRCA1, BRCA1_m , breast cancer gene; BSO, bilateral salpingo‐oophorectomy; CESD, total score of the Center for Epidemiologic Studies Depression Scale; D1, dimension 1; D2, dimension 2; E1G, metabolite of the hormone estradiol; ET_BSO, ever use of estradiol therapy for early life BSO; HC_ever, ever use of hormone contraceptives; MFA, multiple factor analysis; NAART, North American Adult Reading Test IQ; PdG, pregnanediol glucuronide; PSS, total score of the Perceived Stress Scale; RAVLT, Rey Auditory Verbal Learning test; SPWM_errors, total of errors in the Spatial Working Memory Test

FIGURE 2

Group comparison of gray matter volume: (A) shows the two clusters found in the whole brain approach and the gray matter differences among the groups, (B) shows the post hoc analysis revealing greater gray matter loss in BSO group, (C) shows the ROI analysis comparing women with and without SCD, (D) shows the ROI analysis for women with BSO and SCD. AMC, age‐matched control; BRCA1, BRCA1_m , breast cancer gene; BSO, bilateral salpingo‐oophorectomy; GM, gray matter; ROI, region of interest; SCD, subjective cognitive decline; SM, spontaneous menopause