alzheimer’s research reveals critical sex and gender differences in diagnosis and risk
7 minute read
women are almost twice as likely to develop alzheimer's than men.
getty images
women are affected by alzheimer’s disease at nearly twice the rate as men, and new research is now getting a better glimpse into why that may be. it’s long been thought that because women typically live longer than men, it only makes sense that they are far more affected. there were more women over a certain age than men.
historically, research also focused heavily on males, leaving these higher rates of alzheimer’s in women to contend with treatments and interventions that were not tailored to their unique individual experience of the neurodegenerative disease.
as it turns out, biological, hormonal, genetic and sociological factors also come into play regarding the development of alzheimer’s disease in women, opening the door to a new need—research regarding the risk factors and treatment of this form of dementia in women, exclusive to their unique genetic, biological, physiologic and sociologic makeup.
dr. howard chertkow, a canadian cognitive neurologist and chair in cognitive neurology and innovation at baycrest, wears many hats in the world of neurology, spending the bulk of his time researching memory loss, aging and dementia.
during his research, he’s found that the question regarding the reason why women are more likely to get alzheimer’s doesn’t have “a simple answer” because sex and gender are two different things, both of which play a role.
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“sex refers to the biology. you look in every cell of a person, you can see it. two x chromosomes or one x chromosome,” he said. “differences in gender refer to the social and psychological aspects of growing up as a woman versus growing up as a man. so, in fact, there are probably sex and gender differences that are responsible for this.”
he acknowledges that while aging and longevity are the most obvious, they don’t paint the entire picture.
“men have a higher midlife mortality from heart disease, from vascular disease, from cancer,” he said. “so, in that case, particularly for the vascular disease, since this is a big risk factor for dementia and even for alzheimer’s, many men who would have developed alzheimer’s disease may die earlier. so proportionally, more women are alive long enough to get the disease … having said that, there are other things about the biology of women which are important to consider.”
sex differences that drive alzheimer’s disease in women
physiologically, women and men are different. in the case of women and alzheimer’s, the hormone estrogen, which is found in much higher amounts in women, has something to do with higher rates.
as women get older and their body begins to go through perimenopause before eventually reaching menopause, their stores of estrogen drop significantly. according to dr. chertkow, estrogen acts as a neuroprotective hormone in the brains of women until that pivotal period. without adequate levels, that level of hormonal armour is gone.
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“we haven’t evolved to keep the estrogen level high, or when estrogen falls off, it increases the vulnerability of brain cells to many things, and alzheimer’s is likely one,” he said.
the second sex difference revolves around a specific gene, known as the apoe gene, which provides instructions for making a protein known as apolipoprotein e. this protein aids the body in the transport of fats, such as cholesterol, in the body, and helps to maintain several areas of cell health, with a special focus on the brain.
when the variant of that gene, known as apoe e4, is present, it can increase the risk of alzheimer’s development. however, it doesn’t work the same in male and female brains, and “seems to have a more pronounced action in women,” said dr. chertkow. but it doesn’t stop there.
“the third biological aspect is that women, as they age, show greater shrinkage of certain parts of their brain after menopause, the memory-related part of the brain, the hippocampus.”
as a result, they are far more likely to develop symptoms of memory loss.
the role of socioeconomics in alzheimer’s development in women
regarding brain loss, dr. chertkow notes that there is something that people can do throughout their lives to slow or reduce the amount of hippocampus shrinking in the brain, known as cognitive reserve. it involves engaging in stimulating occupations or educational and cognitive activities that keep the brain sharp, so to speak, helping protect it against dementia.
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however, the women who are now reaching the typical age of alzheimer’s onset didn’t have the same access to those activities as men.
“if we look at women in the core of their age, 70, 80, 90, they had less access to education when they were teenagers, in their mid-20s,” he said. “so, this historical cohort of older women has most likely had a lot less cognitive reserve because of factors like education and their ability to get into these stimulating occupations.”
he notes that modern changes in where women fit into the world will hopefully change that for future generations, but as it stands now, it remains a factor in today’s diagnoses of alzheimer’s in women.
he also mentions that since depression is a risk factor for dementia, and more women than men tend to have depression, that’s another piece of the puzzle.
caregiver stress is another area of research being looked at regarding the onset of the neurodegenerative disease, although more research is needed.
“caregivers have a higher rate of getting dementia because we think it’s so stressful, and now one can generalize and say that because women bear much of the brunt of family stress and caregiver stress and looking after everyone’s stress, and we don’t have any way to prove this yet, but maybe this is a factor that puts them more at risk.”
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early detection and the ‘men and women are the same’ issue
work is also being done regarding earlier detection of alzheimer’s in women, but the research is in its infancy, making it harder to say one way or another what differences can be seen.
according to dr. chertkow, there is some evidence to support variations between men and women, that they can continue to work through to try to prepare better for testing.
“we know that from long studies of brain imaging, all the sizes of brains and components of the brain are different,” he said. “so, the science is specifically saying you have to have the norms and the test specifically looking at women versus men, not lumping everyone together.”
he notes that in a perfect world, that would be the case, but in the real world, “that’s probably not done as much as it should be.”
there’s also an issue with how women are diagnosed because of how they present and score on tests during early detection.
“women in general, not all the time, women tend to score higher on verbal memory tests,” he said. “this is the main test we use for diagnosing early memory loss. if they started at a higher level and we lump men and women together, we probably won’t pick up the memory changes in women as quickly as we pick them up in men.”
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because of this, it’s probable that women are experiencing more delays in diagnosis than men as well.
early diagnosis hasn’t been as much of a priority in the past because there were no drugs to use if someone did show early signs to slow progression, but as more disease-modifying therapies become available, “i think we’re going to see a shift in the way doctors and family doctors and specialists view this and i think there will be more emphasis going to what are the reliable tests for the memory tests, the biological tests, the brain imaging tests to make diagnosis early.”
it won’t be an overnight process, though, said dr. chertkow, and people likely have years to wait before that happens.
building on research to create better interventions
while research continues to uncover more clues into alzheimer’s and its genetic and sex differences between men and women, dr. chertkow said that he doesn’t want to “overestimate how far we’ve gone” in the field.
he notes that canada, while ahead of the game regarding sex and gender differences when looking at the experience of women as they age, still operates on the fact that “95 per cent of what we know about biology is based on studying male mice … all the models of diseases are based on male animals and men are highly overrepresented, even in the human studies.”
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even at medical conferences, dr. chertkow has seen evidence that many medical researchers and practitioners continue to believe that male and female diseases are no different, leading to issues with the treatment of these types of diseases that present incredibly differently based on both biological sex and socioeconomic gender factors.
“and, yet, we know that’s not true,” he said. “there is some evidence that some of the anti-alzheimer’s medications coming out may have different efficacy in women and men, and this has to be specifically studied.”
he notes that governments have an important part to play by putting pressure on pharmaceutical manufacturers to see men and women differently, and create and study medications accordingly so that side effects, duration of treatment, dosage and efficacy are all adequately tailored to the sex and gender.
he does acknowledge, though, that in canada, “we’re ahead of the wave here” when it comes to using the default “men and women are basically the same” when it comes to studying diagnoses and disease.
“i’m very proud that the canadian institutes of health research has an institute of gender and health to specifically look at the issues of women,” he said. “and other groups like the women’s brain health initiative, making sure that we are looking at women separately and looking at their issues, as i said, bringing the sex and gender lens to looking at all of these questions is very important.”
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