We’re learning more about how Alzheimer’s disease presents differently in men and women
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Women tend to have more robust verbal memories than men, which can mask signs of early Alzheimer’s disease. This means that commonly used memory tests may fail to pick up on the condition in women, delaying their diagnosis and treatment, according to a new study.
“We are starting to recognise that gender differences in Alzheimer’s is a big issue,” says Ralph Martins at Edith Cowan University in Perth, Australia, who wasn’t involved in the research.
Sasha Novozhilova at McGill University in Montreal and her colleagues analysed data from two large, long-term studies that conducted regular cognitive testing and brain imaging of older adults in the US and Canada, some of whom developed Alzheimer’s disease.
The participants’ cognition was assessed by getting them to learn a list of 15 words that were read to them, then asking them to recall the words immediately, after being distracted with different words, and again later on. This kind of verbal memory test is commonly used in clinical settings as part of investigations for Alzheimer’s disease.
The researchers found that many of the female participants still passed this test even after significant Alzheimer’s pathology had accumulated in their brains, characterised by clumps of misfolded amyloid proteins. On average, they maintained “normal” test scores for 2.7 years longer than male participants with the same pathology.
The reason for this may be that, across the lifespan, it is well-established that women have better baseline verbal memory, on average, than men, says Novozhilova. As a result, they have greater “cognitive reserve” to fall back on when their brains start to be affected by the condition, she says. “Females seem to have better connectivity within their brains, so it might be the case that if one part starts to deteriorate, there are lots of connections around it that can help to maintain normal cognition.”
The problem is that once this reserve eventually runs out, cognition can go downhill quickly and it might be too late to offer treatments, says team member Louis Collins, also at McGill University. New medications like lecanemab and donanemab have been found to slightly slow the progression of Alzheimer’s, but they need to be taken at a relatively early stage in the condition to work, he says. This may explain why women haven’t responded as well to the drugs in clinical trials, because they receive them at a later stage, he says.
“Women’s brains seem to be able to compensate for the accumulating pathology for longer than men’s, but at a certain point, they can no longer compensate, and instead of a slow decline, they have a rapid loss of function,” says Novozhilova. To detect Alzheimer’s disease earlier in women, we may need to interpret their scores on verbal memory tests differently and have different thresholds for considering underlying pathology, she says.
Another option may be to offer screening to all women once they reach a certain age using blood tests that can pick up early Alzheimer’s disease before memory problems become apparent, says Martins. If the condition is detected, there are also non-pharmacological ways to slow its progression, such as through brain training tasks, exercise and the MIND diet, he says.
It is unclear why women have better baseline verbal memory on average, while men tend to remember spatial information better, but there may be evolutionary reasons. In the past, women may have had to hone their verbal skills to effectively communicate with their community and pass knowledge to their children, while men went out to hunt, says Novozhilova. In modern times, a higher proportion of women also work in jobs like writing, editing, nursing, teaching and office administration that may further strengthen verbal memory, she says.
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