Cognitive markers of dementia risk in middle-aged women with bilateral salpingo-oophorectomy prior to menopause

Gervais, Nicole; Au, April; Almey, Anne; Duchesne, Annie; Gravelsins, Laura; Brown, Alana; Reuben, Rebekah; Baker‐Sullivan, Elizabeth; Schwartz, Deborah; Evans, Kelly; Bernardini, Marcus Q.; Eisen, Andrea; Meschino, Wendy S.; Foulkes, William D.; Hampson, Elizabeth; Einstein, Gillian

doi:10.1016/j.neurobiolaging.2020.04.019

Cited by 27 publications

(28 citation statements)

References 38 publications

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“…Despite this, we support exogenous hormone use, specifically estrogen‐replacement therapy, after early surgical menopause to help mitigate the impact of hormonal withdrawal on other end points, including the management of menopausal symptoms as well as cardiovascular and bone health 19,31,32 . One study of 46 BRCA mutation carriers and 25 age‐matched controls recently reported a significant decline in verbal and working memory at least 1 year after oophorectomy and that use of estradiol ameliorated the effect of working memory 12 . It may be that the use of more elaborate, in‐depth, and lengthy tests used in the latter study are capable of detecting more subtle changes in cognitive function.…”

Section: Discussionmentioning

confidence: 95%

“…BRCA mutation carriers represent a group of women who may be at high risk of cognitive decline because they undergo oophorectomy before natural menopause and because many are exposed to systemic chemotherapy and tamoxifen after a diagnosis of breast cancer 11 . To our knowledge, there is only 1 small study that has focused on the BRCA mutation carrier population exclusively 12 . Gervais et al reported a decline in both verbal and working memory after oophorectomy among 46 women with BRCA mutations compared with 25 noncarrier, premenopausal controls.…”

Section: Introductionmentioning

confidence: 99%

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An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool

Kotsopoulos

Kim

Armel

et al. 2021

Cancer

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Background The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation. Methods BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores. Results In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23‐86 years). The mean overall test score was 54.4 (range, 0‐93). The individual subtask scores declined with age at test completion (P < .0001) and increased with level of education (P ≤ .01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P = .01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P = .005). Chemotherapy and hormone‐replacement therapy were not predictive of the overall score. Conclusions These findings are reassuring to high‐risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool

Kotsopoulos

Kim

Armel

et al. 2021

Cancer

Self Cite

View full text Add to dashboard Cite

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“…Early menopause, especially before the age of 40 (either spontaneous or due to bilateral oophorectomy) is associated with an increased risk of MCI, AD, and medial temporal lobe neurodegeneration 89–94 . This risk is most pronounced among women who do not use menopausal hormone therapy (MHT) up until the age of 50.…”

Section: Sex‐specific Risk Factors (Table 3)mentioning

confidence: 99%

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective

Mielke

Aggarwal

Vila‐Castelar

et al. 2022

Alzheimer's & Dementia

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Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk.

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“…Two additional studies were published on the same association after 2019. 9,10 Nevertheless, the association between bilateral oophorectomy and cognitive decline or dementia is not considered established and is not included in mainstream reviews or summaries of the literature on risk factors associated with dementia. [11][12][13] The major reasons for this lack of recognition are the association of age at which the bilateral oophorectomy is performed with cognitive decline or dementia and controversial data about the association of ET after oophorectomy with cognitive decline or dementia.…”

Section: Introductionmentioning

confidence: 99%

Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment

et al. 2021

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IMPORTANCEThe associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial. OBJECTIVE To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance. DESIGN, SETTING, AND PARTICIPANTSThis case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021. EXPOSURES Medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP). MAIN OUTCOMES AND MEASURES Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years. RESULTS Among 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, −0.17; 95% CI, −0.32 to −0.03; P = .02), attention and executive domain z score (β, −0.21; 95% CI, −0.36 (continued) Key Points Question Is bilateral oophorectomy performed before spontaneous menopause associated with later-life cognition? Findings In a case-control ...

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Cognitive markers of dementia risk in middle-aged women with bilateral salpingo-oophorectomy prior to menopause

Cited by 27 publications

References 38 publications

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective

Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment

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