Early bilateral oophorectomy linked to increased Alzheimer's disease risk

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLMDec 9 2024

Women with APOE4 allele and who underwent an early bilateral oophorectomy (BO) were at a higher risk of developing Alzheimer’s disease (AD). In contrast, those with early BO, increased education, and who underwent hormone therapy (HT) were at a lower risk of AD.

Study: Associated risk and resilience factors of Alzheimer’s disease in women with early bilateral oophorectomy: Data from the UK Biobank. Image Credit: Jo Panuwat D/Shutterstock.com

A recent Journal of Alzheimer’s Disease study investigated the risks and resilience factors of AD in women with early BO.

Factors leading to AD development in women

Since elderly women are at a higher risk of developing AD than men, it is pivotal to identify the AD-related risk and resilience factors that could help better manage AD prevalence.

The loss of 17β-estradiol (E2) during menopause was found to be associated with dementia, which is a type of AD, in women. Therefore, more studies are required to understand whether menopause is linked with AD development.

Mostly, spontaneous menopause (SM) occurs in women at approximately 51 years of age. A previous study using UK biobank data revealed that SM could lead to a decline in prospective memory tasks and reduce parahippocampal and hippocampal volume.

Menopause could also occur from surgical removal of both ovaries prior to the average age of SM, and this surgery is called early BO. Unlike SM, where E2 production gradually declines with advancing age, early BO causes sudden loss of endogenous E2 production.

Previous studies have indicated that early BO is associated with higher mortality risk and development of late-life AD. Women who underwent BO surgery prior to age 49 were found to experience greater cognitive decline over a period of up to 18 years.

Furthermore, these women develop multiple comorbidities, such as cardiovascular and pulmonary disease, quickly. It must be noted that many studies that used UK Biobank data have presented mixed findings, particularly concerning the benefits of HT.

About the study

A large population-based cohort study assessed whether early BO, i.e., BO prior to SM, increases the risks of AD development. This study hypothesized that women undergoing early BO are at a higher risk of AD than women with SM.

This study also hypothesized that the APOE4 allele in women undergoing early BO also increases the odds of AD incidence.  Furthermore, the authors hypothesized that women with early BO and who had undertaken HT were at a reduced risk of AD development than those who did not use HT.

All relevant data for this study were obtained from the UK Biobank. The samples were restricted to older women, i.e., 60 years of age or older, who either had BO at 49 years of age or younger or SM at 51 years of age or older. Women who had BO at age 49 or younger were only considered to capture the effect of BO and not SM.

To determine the risk and resilience factors for different menopauses linked with AD incidence, the current study directly compared and analyzed women with early BO sans AD (BO), women with early BO and AD (BO-AD), women with SM sans AD (SM), and women with SM and AD (SM-AD).

Study findings

This study recruited 34,603 participants, BO: 4356; BO-AD: 47; SM: 30,139; and SM-AD: 61. At baseline, the participants' average age was 63.8, and they had 13.0 years of education. Approximately 25% of the cohort had an APOE4 allele.

Statistical analysis, including ANOVA and Tukey's HSD test, revealed that APOE4, HT, education, age at menopause, and body mass index (BMI) are the potential risk and resilience factors for women with early-life BO.

In comparison to SM, early BO increased the odds of AD incidence by four times. Participants with early BO were more inclined to use HT. Individuals with BO and who had developed AD were more likely to be APOE4 carriers and have been diagnosed with cancer.

The combined menopause type model indicated that each additional year of education and HT use decreased AD risks. It also associated APOE4 allele and older age with higher odds of AD.

Similar observations were also obtained in the stratified model for the BO group, and sensitivity analysis was conducted on all women who attained SM above 40 and BO below 49.

The current study revealed that age at menopause did not significantly contribute to AD development.

Conclusions

The current study identified the risks and resilience factors associated with AD in women with early BO to be age, BMI, APOE4, education, and HT. A higher risk of AD was associated with ovaries removal and not menopause.

Interestingly, education was found to be associated with decreasing the risk of cognitive decline and odds of AD. In the future, more research is required to determine whether a particular HT type, duration, and route of administration could influence AD incidence.