A groundbreaking study from the Universities of Toronto and Alberta found that women who have bilateral oophorectomy (the surgical removal of both ovaries) before they turn 50 have a much higher chance of getting Alzheimer's disease (AD) if they have the APOE4 genetic variant. The Journal of Alzheimer's Disease published the study, shedding light on important risk and resilience factors. For example, it shows how hormone therapy, schooling, and body mass index (BMI) can lower or raise the risk of Alzheimer's in old age.

Using data from the UK Biobank, the study looked at a group of 34,603 women and found that women who had an early bilateral oophorectomy had four times the chance of Alzheimer's as women who were going through natural menopause. Many fewer women developed the disease during their natural menopause, which occurred at an average age of 54. Loss of oestradiol, an endogenous oestrogen, and the presence of the APOE4 allele—a genetic trait known to raise the risk of Alzheimer's—were closely linked to this higher risk.

Lead researcher and professor at the University of Toronto, Dr. Gillian Einstein, talked about how this group of people is in double danger. Einstein said, "Loss of naturally occurring oestradiol due to ovarian removal interacts with the APOE4 allele to greatly increase the risk of Alzheimer's." Given that women account for two-thirds of all cases of Alzheimer's, a trend currently under investigation, this finding sheds light on the differences between men and women who develop the disease.

The study found that hormone treatment might protect women who have an early oophorectomy from getting Alzheimer's. People who used hormone therapy based on oestrogen had less than half the risk of getting Alzheimer's disease compared to people who did not use hormone therapy. For example, this shows how estrogen can help protect brain health. But hormone therapy didn't seem to help women who went through natural menopause much, according to the study. 

Dr. Esme Fuller-Thomson, co-author and director of the Institute for Life Course & Aging at the University of Toronto, said, "This shows how important estrogen-based therapies are for lowering the risk of Alzheimer's in women who lose ovarian function early."  However, the fact that natural menopause doesn't have any effect shows how important the time and hormones are.

Higher levels of education were linked to a 9% lower risk of Alzheimer's for women going through both types of menopause, showing that it was a strong predictor of resiliency. This finding backs up an earlier study that says cognitive engagement makes the brain stronger. Also, researchers found an unexpected link between BMI and Alzheimer's risk: for women who had an early oophorectomy The Journal of Alzheimer's found that the risk decreased by 7% for every unit of BMI.

The study's first author and postdoctoral researcher, Dr. Noelia Calvo, explained this surprising finding by saying, "Adipose tissue produces oestrone, which might partially compensate for the loss of oestradiol, thereby protecting cognitive function in early middle age."

Alzheimer's is expected to affect 12.7 million people aged 65 and up by 2050, with women making up two-thirds of that group. This study identifies a crucial early-life factor that contributes to this disparity and demonstrates how hormone therapy and educational approaches can reduce risk. Researchers emphasize the critical need for further research to enhance these methods, particularly for women with genetic susceptibility to harm.

Einstein said, "Our results strongly suggest that early bilateral oophorectomy, along with APOE4 and oestradiol loss, accounts for a substantial portion of the difference between male and female Alzheimer's cases." Also, and this is very important, they show us ways to make ourselves stronger against this terrible disease.