Cerebral CorteXX:Gillian Einstein’s Work on the Aging Female Brain is Changing the Way We Look at Human Health

Jennifer McIntyre
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University of Toronto researcher Dr. Gillian Einstein has been investigating why brain disorders like Alzheimer’s disease, stroke, and dementia occur more frequently in women than in men.

Her lab recently received a welcome financial boost: in December 2016, Einstein, a distant cousin of physicist Albert Einstein, was awarded the inaugural Wilfred and Joyce Posluns chair in Women’s Brain Health and Aging, which comes with $1 million over five years.

“The goal of the chair,” explains Einstein, “is to advance our understanding of women’s brain health and aging. My own focus is on how hormones, or a loss of hormones, might affect that.”

Her interest in the field began when she was an art history undergraduate at Harvard, with a seemingly casual question about how we see.

“I got interested in the brain because of my interest in vision. I really wanted to understand how people see things,” she says. “I’ve always really loved art, but in terms of a profession, I wanted to do something more, to understand the mechanism [of vision] a little bit more.”

Einstein enrolled in the then-new neurobiology program at the University of Pennsylvania, where she ultimately earned her PhD in neuroanatomy. From there, she went on to do research in vision and Alzheimer’s disease at Duke University. The link between the two might not seem clear, but to Einstein, the connection was obvious.

“The occipital lobe, the part of the brain I was studying, [plays a part] in Alzheimer’s disease. The occipital lobe [the brain’s visual processing centre] itself is not affected, but the other regions of the brain with which it communicates are affected. These other regions affect [a person’s] interpretation of the visual scene.”

She then began to question why Alzheimer’s is more prevalent in women. Previously, it was assumed that this was mainly because age is the largest risk factor for the disease, and women tend to live longer than men.

But Einstein suspected other factors were at play, like the unique life stresses experienced by women (such as caregiving responsibilities, sexual violence, and economic inequalities) and the effects of hormones like estrogen that diminish as a woman ages.

Currently, she says, “my focus is on how hormones, or a loss of hormones, might affect [the brain]— through menopause, through having one’s ovaries removed, through having ovarian failure for any reason. I’m studying memory and attention in women who carry the BRCA mutation, who’ve been advised to have their ovaries removed to protect them from the risk of breast and ovarian cancer.”

“The results are very preliminary—we’re still recruiting for the study—but we are finding changes.”

There have been several landmark studies on how various stimuli change the male brain, but very few focusing specifically on women. The “cortical homunculus,” a well-known representation of the human brain depicting where sensations from various body parts are processed, references the male body, not the female.

“There is no map of the female body and the brain,” Einstein says. “We know that the map of male [brains] changes. There’ve been famous studies of violinists, cab drivers, and so forth, but we really haven’t studied females. 

“[In my early research] I was trying to understand what might happen to that map for women who had experienced female genital cutting. I started scouring the literature and found there wasn’t anything for women on that map. I think it would be great to make that map. Qualitatively it may resemble the male map, but it may also be a map that changes—for example with the menstrual cycle, at different reproductive stages, with pregnancy, and so forth.”

She refers to her imaginary female diagram as the “hermunculus.”

“I’d love to be able to do it,” she enthuses. “I would like to look for funding, but it’s not something I’ve started yet.”

There are several important implications for her research on hormones and the brain.

“First, I’d like us to better understand the importance of hormones for healthy brain aging in women,” says Einstein. “In the broader picture, I would like a smart biophysicist to design a method for visualizing the ovaries so they could be followed over time. It would be better if you could tell when the ovaries were beginning to have cancer so they could be removed then, rather than removing healthy tissue.

“The ovaries produce hormones that are important for the brain, but also for every body system. So, it would be best if people could keep them. Right now, however, for women with the BRCA mutation, [removal] is the best prophylaxis.”

Einstein is adamant, however, that her research is not just “women’s research.”

“I think people in science want their work to be broadly generalizable. But [in the past], people only studied males and then generalized those findings—I think that’s a problem.”

She applauds the recent changes in several key research funding bodies, for example the Canadian Institutes of Health Research and the National Institutes of Health in the US, both of which now require scientists to justify their work if they are studying only males or only females.

“It’s becoming much more important in the field of dementia research to think about this as well: Who are the people who get Alzheimer’s disease? The greater proportion are women, so why aren’t we trying to understand how it’s the same or different in men and women?

“And why aren’t we thinking about women when we design clinical trials for drugs?” she continues. “We need to think about dosing, and about developing drugs that might be effective in women and not so effective in men and vice versa. Drugs have been taken off the market because they were extremely effective in men but not in women. Why don’t we leave them on the market for men?

“Even in Alzheimer’s disease, a lot of the drugs are tried on women because most of the people are women—and again it’s then assumed they’re going to work for men. So, we’re back to the larger issue of this being important for human health.”

Her lab has also examined cognitive issues in LGBTQ communities as part of the larger issues surrounding sex, gender, and brain health.

“We also need to think more broadly about, for example, trans health, about the long-term effects of taking hormones. That’s one of reasons why we did the trans cognition project [Transgender Cognition and the Origins of Gender Dysphoria],” which studied the impact of cross-sex hormones on thinking, memory, and attention,

This latter aspect of her research was greatly enhanced, she stresses, by the diverse and inclusive atmosphere of University College.

“I really value the UC community, the openness to ideas and the trans-disciplinary nature of what goes on there,” says Einstein warmly. “I’ve found it a very welcoming place.”

She is eager to get more researchers to consider sex and gender differences when they’re designing their studies, and to include women in their research. These seemingly simple steps will not only fill a yawning gap in the existing research, but enhance the relevance of research findings overall.

“I think there are a lot of similarities between people who are XX and people who are XY,” she says.

“But where there’s difference, we need to acknowledge it.”