Women are far more likely than men to end up with Alzheimer’s disease (AD). This may, at least partially, be due to women’s longer average lifespans, but many scientists think there is probably more to the story. It would be easy to surmise that the increased risk is also related to differences in the way men’s and women’s brains change as they age. However, the research thus far has been unclear, as results across different brain regions and methods have been inconsistent.
Now, a new study, published in Proceedings of the National Academy of Sciences, indicates that it’s men who experience greater decline in more regions of the brain as they age. Researchers involved in the study analyzed 12,638 brain MRIs from 4,726 cognitively healthy participants (at least two scans per person) from the ages of 17–95 to find how age-related changes occurred and whether they differed between men and women.
The results showed that men experienced declines in cortical thickness and surface area in many regions of the brain and a decline in subcortical structures in older age. Meanwhile, women showed greater decline only in a few regions and more ventricular expansion in older adults. So, while differences in brain aging between the sexes are apparent, the cause of increased AD prevalence in women is still a bit mysterious.
“These findings suggest that the higher prevalence of AD diagnoses in women likely stems from factors beyond differential rates of age-related brain atrophy,” the study authors write.
One factor that might be to blame is genetics, particularly the APOE ?4 allele, which may affect protein accumulation in the brain and work differently in men and women. Other factors might include differences in hormonal changes, diagnosis patterns, and sociocultural influences.
Survival bias may also skew the results in AD studies, as more men may have been diagnosed with AD if their average lifespans matched women’s more closely. In this particular study, participants were also more educated on average, which is a protective factor for AD—leading to a potential representativity bias.
When the researchers corrected for life expectancy, they say some of the differences did clear up for men and additional differences cropped up in women.
“The interpretation of these sex differences is complicated by our life expectancy analyses, which removed several cortical decline effects in men while revealing effects in women, including greater hippocampal decline. Whether this reflects the removal of proximity-to-death artifacts or elimination of biological aging differences cannot be determined, and these findings should be interpreted with caution, especially considering representativity bias in our sample with potentially healthier men,” the authors explain.
It’s clear that more research is needed, but the study has overall let researchers get a step closer to understanding the mechanisms behind Alzheimer’s disease by addressing the questions they set out to answer about how the brain changes with age.
Written for you by our author Krystal Kasal, edited by Gaby Clark, —this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive.
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More information:
Anne Ravndal et al, Sex differences in healthy brain aging are unlikely to explain higher Alzheimer’s disease prevalence in women, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2510486122
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