A large international study has found that the human brain shrinks with age at different rates in men and women. Researchers discovered that men experience faster and more widespread brain volume loss than women, though this does not necessarily explain why women are more frequently diagnosed with Alzheimer’s and dementia.
Dr. Sandra Benizri, a neurologist at Assuta Medical Centers, said: “There isn’t necessarily a direct connection between brain volume loss and cognitive decline. In fact, certain cognitive functions may even improve with age."
The human brain naturally shrinks with age, but among Alzheimer’s patients, this process is significantly faster and more severe. Although women are diagnosed with the disease at twice the rate of men, little is still known about how biological sex difference influences brain volume loss over a lifetime.
The study, conducted at the University of Oslo and published in the journals PNAS and Nature, analyzed more than 12,000 brain scans from 4,726 cognitively healthy individuals aged 17 to 95. Each participant underwent at least two MRI scans, with an average interval of three years.
A gender gap in brain aging
After controlling for sex-based differences in brain size, the team found that men showed a decline in a greater number of brain regions, including many parts of the cortex, in older age. This area of the brain is responsible for high-level cognitive functions such as memory, language and decision-making.
Women, in contrast, showed a decline in fewer regions, and the thickness of their cortex was less altered with age, suggesting a slower and milder process of brain degeneration.
"If women's brains declined more, that could have helped explain their higher Alzheimer's prevalence," co-author Dr. Anne Ravndal, a neuroscientist at the University of Oslo in Norway, told Nature.
The findings suggest that there are real sex differences in the biology of aging, but the results should be interpreted with caution, the authors note, as the observed volume loss was mild but consistent, and not necessarily tied to a decline in function. Long-term studies are still needed to explore whether these differences affect cognition, memory or the development of age-related neurological diseases.
“This is a complex issue under broad scientific debate, and existing research doesn’t always reach the same conclusions,” said Dr. Benizri. “We know that Alzheimer’s is more common in women than in men, but the reason remains unclear. Researchers are looking at various factors, including average brain size, typically larger and heavier in men, as well as the pace of shrinkage with age and whether the process unfolds differently between genders."
Not all brain shrinkage points to dementia
Researchers found sex-based differences in total brain volume and other structural features such as cortical thickness, surface area and subcortical brain volume involved in sensory and cognitive functions. Surprisingly, they found no difference in volume changes to the hippocampus – a neural hub for memory and learning closely involved in dementia and neurodegenerative diseases.
Only in older age did women in the study begin to show a faster decline in the hippocampus, once their relative life expectancy was taken into account. But this may simply be a delay in aging: a product of women living longer than men and not necessarily a sign that explains their higher rates of Alzheimer’s disease.
According to Dr. Benizri, brain shrinkage with age is a natural process, much like skin changes over time. Still, there isn’t necessarily a direct link between brain volume loss and cognitive function. In fact, some cognitive processes may even improve with age. It’s a more complex mechanism that depends on which brain areas are involved, how quickly the process unfolds and the person’s age", she said.
Benizri noted that while brain shrinkage is generally correlated with dementia, it is not a definitive indicator. “We can measure shrinkage through brain MRIs, but when patients are told their brain has shrunk, that doesn’t automatically mean something is wrong,” she said. “In most cases, it’s a normal part of aging and doesn’t necessarily indicate dementia. While brain shrinkage does occur in dementia, not all shrinkage signals the disease."
Age can narrow the gender gap
When researchers compared men and women who were predicted to live the same amount, some of the brain decline between the sexes balanced out. This suggests some of the observed gaps may stem from general differences in longevity rather than from distinct biological aging processes.
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Dr. Benizri: "If a brain MRI shows shrinkage, one should not rush to conclusions"
(Photo: shutterstock)
Despite extensive investigation into the biology of the aging brain, there remains an extreme sex bias in the field. In 2019, only 5 percent of published studies in neuroscience or psychiatry considered the influence of sex on brain structure.
As a result, the overall picture remains inconclusive. Some studies show steeper brain shrinkage among men, while others show steeper declines among women.
The current research sought to clear up the picture, suggesting that between the sexes, researchers found sex-based differences, but they may not directly account for the higher incidence of Alzheimer’s among women.
The team emphasized that teasing apart the impact of sex on the brain from other genetic, environmental and social factors is particularly challenging, as there is lack of large-scale longitudinal research in the field. Therefore, many questions about brain degeneration are left unanswered.
A 2023 scientific review argued that the continued scientific bias in brain aging studies has "grave consequences" for wellbeing and places a "disproportionate burden" on female health.
Dr. Benizri concluded: “It’s important to stress that if a brain MRI shows shrinkage, one should not rush to conclusions. This is often a natural effect of aging and doesn’t necessarily signal cognitive impairment. Many other factors beyond shrinkage alone can influence the development of dementia."