From body to brain: Understanding how sex and gender contribute to brain health as we age
Why do more women develop Alzheimer's disease than men?
This is a question that has intrigued medical doctors, psychologists, and scientists for decades. Among those is Dr. Gillian Einstein, a neuroscientist and professor of psychology at the University of Toronto.
"More than two-thirds of Canadians who have Alzheimer's disease are women," says Dr. Einstein, who also holds the Wilfred and Joyce Posluns Chair in Women's Brain Health and Aging. "We don't exactly know why, but it may be a combination of many factors, biological and social, both of which can affect the brain. There have been some studies that suggest it may have something to do with the loss of hormones as women age, but we need to do more research to understand what other factors are involved."
Dr. Einstein is currently exploring how sex (the anatomical and physiological characteristics we are born with) and gender (the behavioural, cultural, and psychological traits associated with social expectations and norms, as well as our identity) affect brain changes as we age, as well as the role that social factors and lived experiences play. Specifically, her team in the Einstein Lab recruits women, men, and gender-diverse individuals to study how their brains and behaviour react and respond when they experience sex-specific health conditions, medical treatments, or social practices.
"The brain is not autonomous; our brain, our body, and our environment are intertwined," Dr. Einstein explains. "So, while brain development and function are influenced by genetics, hormones, and sex and gender, they are also influenced by culture, social environment, and life experiences. Through my work, I am interested in understanding if – and how – women's experiences in early life effect their brain development as they age, and whether certain experiences could increase their risk of developing Alzheimer's disease in their later years."
Understanding the link between lived experience and brain development
The human brain is highly interconnected with the rest of our body, which regulates how we function, feel, and think. This interconnectivity can have its downsides, however, because events, conditions, or medical procedures that directly affect one part of our body can leave a long-term mark on the brain as well.
For example, Dr. Einstein points to a 2007 epidemiological study in the United States that inspired several of her current research studies. In the 2007 study, it was found that women who had their ovaries surgically removed before the age of 50 – which is before they would naturally experience menopause – had higher rates of late-life dementia and Alzheimer's disease, compared to women who kept their ovaries. When Dr. Einstein read those results more than a decade ago, she knew she needed to find more answers.
Dr. Einstein and her team launched their own study focused on women who had their ovaries removed between the ages of 30 and 60 to explore the long-term effects of this experience on their cognition (thinking, attention, and memory). Using brain-imaging, neuropsychological testing, and qualitative interviews, they are monitoring participants' brain changes, functioning, and behaviour from one year post-surgery to 10 years post-surgery.
"There are medical reasons for ovary removal, but it's worth keeping in mind that patients are then living the rest of their lives – sometimes 20, 30 or 40 years – without the benefits of ovarian hormones," Dr. Einstein explains. "What we don't know is how this will affect their brain and behaviour over those years. What happens to their memory as they age? What happens to their immune system and sleep patterns? What happens to the whole body, including their sense of self and who they are? These are all the questions we want to find answers to through this study."
Supporting women who are at risk of developing cancer
One of the reasons patients opt for ovary removal has to do with cancer risk. For example, women who carry specific mutations in what are known as the BRCA1 and BRCA2 genes have a much higher-than-average risk of developing breast and ovarian cancers. As a result, some of these women choose to have their ovaries removed as a way of pre-emptively reducing their risk of developing cancer later in life.
"Choosing to have your ovaries removed is not a decision you make overnight," Dr. Einstein says. "It requires a lot of contemplation and understanding of the potential implications. When it comes to women who carry the BRCA gene mutation, yes, having this surgery will reduce their likelihood of developing cancer – but if it will potentially increase their chances of developing Alzheimer's disease, then we want them to be aware of that, too."
It is for this reason that all the women recruited for her team's study carry the BRCA gene mutation. The study is still underway, but Dr. Einstein believes the information gathered over the coming years will be useful for women who are considering having preventive surgery in the future, as well as for those who have already elected to have this procedure. More broadly, the study will provide new insights into the effects of estradiol, one of the many estrogens, and estradiol withdrawal on cognition and memory, which has the potential to benefit all women, especially if it helps lead to new therapeutics and brain health interventions.
"Considering women generally live longer than men and are affected by age-related brain health disorders more often than men, the work we're doing is really important – not only to understand the health of aging women, but also to inform policies and solutions that can help promote wellness in aging more broadly," she says. "Aging is a gift. Our work is simply about ensuring it's a healthy one."
The Wilfred and Joyce Posluns Chair in Women's Brain Health and Aging is an initiative of the late Wilfred Posluns' Family Foundation and the Women's Brain Health Initiative. It is supported through a partnership between the Foundation, the Canadian Institutes of Health Research (CIHR), Alzheimer Society of Canada, and the Ontario Brain Institute.
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