Early bilateral oophorectomy linked to increased Alzheimer’s disease risk

Women with APOE4 allele and who suffered it Early bilateral oophorectomy (BO) were at higher risk of developing Alzheimer’s disease (AD). In contrast, those with early BO, higher education, and undergoing hormone therapy (HT) had 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 credits: Jo Panuwat D/Shutterstock.com

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

Factors leading to AD development in women

Because older women are at higher risk of developing AD than men, it is critical to identify the AD-related risk and resilience factors that can help better control AD ​​prevalence.

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

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

Menopause can also occur due to surgical removal of both ovaries before the average age of SM, and this surgery is called early BO. Unlike SM, in which E2 production gradually decreases with aging, early BO causes a sudden loss of endogenous E2 production.

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

In addition, these women quickly develop multiple comorbidities, such as heart and lung diseases. It should be noted that many studies using data from the UK Biobank have produced mixed findings, especially regarding the benefits of HT.

About the study

A large population-based cohort study assessed whether early BO, that is, BO prior to SM, increases the risk of developing AD. This study hypothesized that women undergoing early BO are at higher risk for AD than women with SM.

This study also assumed that the APOE4 allele in women undergoing early BO also increases the risk of AD incidence. Furthermore, the authors hypothesized that women with early BO and who had undergone HT were at lower risk of developing AD than those who did not use HT.

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

To determine the risk and resilience factors for different menopause events associated with AD incidence, the current study included women with early BO without AD (BO), women with early BO and AD (BO-AD), women with SM without AD (BO-AD) directly compared and analyzed. SM), and women with SM and AD (SM-AD).

Findings of the study

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

Statistical analysis, including ANOVA and Tukey’s HSD test, revealed that APOE4HT, education, age at menopause and body mass index (BMI) are the potential risk and resilience factors for women with BO at a young age.

Compared with SM, early BO increased the odds of AD incidence by fourfold. Participants with early BO were more likely to use HT. Individuals with BO and who had developed AD were more likely to develop this APOE4 are carriers and have been diagnosed with cancer.

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

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

The current study found that age at menopause did not significantly contribute to the development of AD.

Conclusions

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

Interestingly, education was found to be associated with reducing the risk of cognitive decline and the likelihood of AD. In the future, more research is needed to determine whether a particular HT type, duration, and route of administration can influence AD ​​incidence.