A recent study published in the Journal of Alzheimer’s Disease has delved into the risks and resilience factors for Alzheimer’s disease (AD) among women who have undergone an early bilateral oophorectomy (BO).
As elderly women are at a greater risk of developing AD compared to men, it’s crucial to pinpoint the risk and resilience factors related to AD to better manage its prevalence. The loss of 17β-estradiol (E2) during menopause has been associated with dementia, a form of AD, in women. Hence, more research is needed to understand the link between menopause and AD development.
Typically, spontaneous menopause (SM) occurs in women around the age of 51. A prior study using UK Biobank data showed that SM could lead to a decline in prospective memory tasks and a reduction in parahippocampal and hippocampal volume.
Menopause can also result from the surgical removal of both ovaries before the average age of SM, which is known as early BO. Unlike SM, where E2 production gradually decreases with age, early BO causes a sudden loss of endogenous E2 production.
Previous studies have indicated that early BO is linked to a higher mortality risk and the development of late-life AD. Women who had BO surgery before age 49 were found to experience greater cognitive decline over up to 18 years and developed multiple comorbidities like cardiovascular and pulmonary diseases quickly. It’s worth noting that many studies using UK Biobank data have presented mixed findings, especially regarding the benefits of hormone therapy (HT).
A large population-based cohort study was conducted to assess whether early BO (before SM) increases the risks of AD development. The study hypothesized that women undergoing early BO are at a higher risk of AD than those with SM. It also hypothesized that the APOE4 allele in women with early BO increases the odds of AD incidence and that women with early BO who had undertaken HT were at a reduced risk of AD compared to those who didn’t use HT.
All relevant data for this study were obtained from the UK Biobank. The samples were limited to older women aged 60 or older, who either had BO at 49 or younger or SM at 51 or older. Women with BO at 49 or younger were considered to isolate the effect of BO rather than SM. To determine the risk and resilience factors for different menopausal states linked to AD incidence, the study directly compared and analyzed women with early BO without AD (BO), women with early BO and AD (BO-AD), women with SM without AD (SM), and women with SM and AD (SM-AD).
The study recruited 34,603 participants: 4,356 in the BO group, 47 in the BO-AD group, 30,139 in the SM group, and 61 in the SM-AD group. At baseline, the participants had an average age of 63.8 and 13.0 years of education. Approximately 25% of the cohort had an APOE4 allele.
Statistical analyses, including ANOVA and Tukey’s HSD test, revealed that factors like APOE4, HT, education, age at menopause, and body mass index (BMI) are potential risk and resilience factors for women with early BO. Compared to SM, early BO increased the odds of AD incidence by four times. Participants with early BO were more likely to use HT. Those with BO who had developed AD were more likely to be APOE4 carriers and have been diagnosed with cancer.
The combined menopause type model showed that each additional year of education and HT use decreased AD risks, while the APOE4 allele and older age were associated with higher odds of AD. Similar observations were obtained in the stratified model for the BO group, and sensitivity analysis was conducted on all women with SM above 40 and BO below 49. The study also found that age at menopause did not significantly contribute to AD development.
The current study identified age, BMI, APOE4, education, and HT as the risks and resilience factors associated with AD in women with early BO. A higher risk of AD was linked to the removal of ovaries rather than menopause itself. Interestingly, education was found to be associated with reducing the risk of cognitive decline and the odds of AD. In the future, more research is needed to determine if specific aspects of HT, such as type, duration, and route of administration, could influence AD incidence.
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