Abstract

AbstractBackgroundNearly two‐thirds of individuals with Alzheimer’s disease (AD) are women, and the lifetime risk for AD is twice as high in women compared to men at age 45 (Alzheimer’s Association, 2019). Despite this increased prevalence, little is known about why more women develop AD. Early life events affecting 17β‐estradiol (E2) may be a potential mechanism behind this sex difference. E2 and/or ovarian loss leads to cognitive decline and neurodegeneration, which is mitigated with E2 (Gervais et al., 2020; Kantarci et al., 2018; Zeydan et al., 2019). Further, women with bilateral oophorectomy have an increased risk of AD in later life (Rocca et al., 2007). However, little is known about the long‐term trajectories of cognitive change post‐oophorectomy.MethodThe current study investigated cognitive decline over time in older women with bilateral oophorectomy (BO; n = 30; total visits = 131) prior to age 45 compared to spontaneously menopausal (SM; n = 61; total visits = 277) women from the Baltimore Longitudinal Study of Aging (BLSA; Shock et al., 1984). All participants were free of any dementia and completed a variety of demographic and cognitive assessments. Each eligible BO participant was age‐matched at a 1:2 ratio with a SM participant. Data were analyzed using linear mixed‐effects models in R 3.6.1 (R Core Team, 2019).ResultParticipants completed an average of four visits over 11‐years, and ranged in age from 52‐91 years. Our analyses revealed the BO group recalled significantly less words on the California Verbal Learning Test and made significantly more errors on the Benton Visual Retention Test over time than the SM group. Additionally, the BO group had poorer Digits Backward and Letter Fluency performance over time compared to the SM group.ConclusionResults demonstrate an association between BO prior to age 45 and greater longitudinal decline in executive function, verbal memory, visual memory, and working memory performance compared to age‐matched, spontaneously menopausal women. This is the first study to evaluate continuous cognitive decline post‐oophorectomy from midlife to older age, and suggests that even in normal aging, the early loss of E2 via BO may confer long‐lasting effects on cognition spanning decades of life.

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