why are women more at risk for alzheimer's disease than men?

research is showing differences in the ways that women's brains change compared to men's, a finding that might help scientists develop early interventions to prevent disease.

by robin roberts

published dec 19, 2022

6 minute read

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6 minute read

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women tend to develop alzheimer's later, but they progress quicker

women experience poorer health from missed diagnoses, minimized symptoms, and poorly targeted treatment compared to men. getty

women comprise half the world’s population yet are largely under-represented in health studies. in neuroscience specifically, they factor in at as little as three per cent. yet, according to the centre for addiction and mental health, women have higher rates of mood disorders such as depression and anxiety. they are also three times more likely than men to develop dementia, which affects about 600,000 canadians, reports the alzheimer society of canada.

and, according to ubc’s women’s health research cluster, “women experience poorer health from missed diagnoses (when they are diagnosed, it’s two years later for the same disease as a man’s), minimized symptoms, greater burdens of specific diseases, and poorly targeted treatment compared to men.”

female scientists are all too aware of the long-standing disparity — in the incidence in alzheimer’s disease, poor diagnoses, and study subjects — despite more women entering the health and science fields. typical reasons given are that, historically, more men than women are employed in health sciences and there’s likely a self-interest at stake; that women, because of their biological makeup (menstrual cycle, pregnancy, menopause), are too complicated to study; and because, if women are included in studies, twice as many participants are needed, which makes them more expensive.

there’s also the claim that women have “atypical” symptoms for such conditions as depression or heart attack.

“atypical symptoms to who?” wonders dr. liisa galea, who is the treliving family chair for women’s mental health, and a senior scientist at the campbell family mental health research institute. “for women, who are half of the population or more, they’re not atypical. if your standard is always male physiology and what men’s symptoms look like, of course you’re going to think they’re atypical. some [researchers] will interpret a difference between men and women as women being inferior. who sets that? why can’t it be that men are inferior? it’s not that one is inferior to the other, it’s just that we’re different. and because of these differences, we have different physiological needs and different susceptibilities to disease.”

galea, who is also a professor in university of toronto’s department of psychiatry, lead at ubc’s research cluster, focuses her research on the biological reasons that women are at a greater lifetime risk for alzheimer’s disease and depression — research that could ultimately benefit men also. “if we find a treatment that doesn’t work in females but [may] work in males, that’s good for the men in our lives,” she says.

the brain on hormones

galea emphasizes that her work looks at not just the prevalence of disease but how the manifestation of the symptoms may differ between men and women, and how hormones might be contributing to those differences. to wit: the huge upheaval due to sex hormones in the minds and bodies of adolescents going through puberty. as well, pregnancy, she says, pumps a cascade of hormones through the system, in turn affecting the body and brain — and not entirely negatively.

“there’s been some interesting research coming out of norway that looked at thousands of women’s brains [that found that] women who had pregnancies showed less evidence of clinical brain aging,” she says, adding that the finding is likely due to biological changes during pregnancy. “there’s [also] a reduction in risk to develop certain kinds of cancer after giving birth — sometimes for 10 to 20 years for breast and uterine cancer. so it’s not surprising that [the effect of hormones] might extend to other kinds of diseases as well.”

dr. gillian einstein, faculty member in the department of psychology at the university of toronto, adjunct scientist at the women’s college research institute, and a member of both the institute for life course & aging and the bonham centre for sexual diversity studies at the university of toronto, also delves into the relation of hormones to brain health by zeroing in on ovaries, where the female hormones estrogen and progesterone are made. at her einstein lab, she also explores how the brains of women, men and gender-diverse individuals respond when they experience sex-specific health conditions, treatments and practices.

as the wilfred and joyce posluns chair in women’s brain health & aging, einstein (yes, she’s a distant relative of the more famous einstein) is studying women who have had their ovaries removed before the age of 49, when they would naturally go into menopause.

“we found that, within five years of their surgery, they have decrements in remembering words and stories, and in remembering things for a short period of time, called working memory,” she says. “the region of the brain that plays a role in verbal memory has a sub-region that is smaller in volume in women who have had their ovaries removed before 49 if they do not have hormone replacement. and if they take estradiol [estrogen hormone] replacement, their short-term memory improves. [but] it’s not a silver bullet. it works for some areas of cognition and not necessarily for others. it’s more successful in some people than in other people [which] makes it really hard to know how to prescribe it.”

einstein notes other studies that have shown that the younger the women who had their ovaries removed, the steeper the cognitive changes. “the risks for having late life dementia for women who have had their ovaries removed before the age 49 is about twice that of women who keep their ovaries.”

she says researchers are looking at brain and cognitive changes earlier “because we’re beginning to realize that you don’t just one day get alzheimer’s disease when you’re 75 years old; it’s a long process. and because there are no successful treatments for alzheimer’s disease, people are trying to understand what the earliest stages might look like so we can possibly intervene with lifestyle factors like exercise, diet, sleep.”

(the brain health initiative itemizes the six pillars of brain health that could lower the risk.)

gender impact on alzheimer’s

it’s widely assumed that women are at greater risk for alzheimer’s disease because they typically live longer than men, and age is a risk factor (although not always, since some experience dementia in their forties and fifties). but it’s not the sole reason.

“the data is there that there’s something unique that sets the stage for more alzheimer’s in women,” says einstein. “[but] i don’t think the jury’s in. whatever the case, there certainly are differences in some of the earliest brain changes. women tend to get alzheimer’s disease later than men but once they get it, they progress more quickly. women also maintain their verbal memory longer than men do.”

so, armed with all this knowledge, why is it that every new “breakthrough” drug seems to disappoint? “that’s a very deep and important question that doesn’t have a simple answer,” says einstein. “it may be that people are looking at the wrong problem. alzheimer’s disease research has focused for a long time on plaques, and most of the therapies that are being developed are designed to get rid of, or prevent, the plaques. but plaques may not be causative. we need to think a bit more broadly, but i’m not a clinical trials person for alzheimer’s. i’m more interested in early life interventions and the possibilities that things that we do to ourselves might increase our risk factors. the earlier we are able to identify when changes start and what they are [the earlier] we can come up with lifestyle interventions that could be very important in slowing the progression of change.”

meanwhile, galea is optimistic that a shift is happening, albeit slowly, in how the genders are studied and treated. “i don’t believe we’ll get to where we need to be in terms of our understanding of body and mind until we consider gender as a factor in our studies,” she says. “it’s important to study these differences because it can lead us to better diagnoses and treatments more quickly, no matter your gender.”