Men’s brains may age faster than women’s, according to a new study that complicates long-held assumptions about why women face a higher risk of Alzheimer’s disease. Brain ageing is one of the strongest risk factors for Alzheimer’s, the most common form of dementia, and differences in how male and female brains change over time have been closely studied in an effort to explain why women are almost twice as likely to develop the disease.
The new research, published in Proceedings of the National Academy of Sciences, suggests that the explanation may not lie in faster brain ageing among women, after all. The findings indicate that male brains tend to deteriorate more rapidly across several regions, even among people who are otherwise healthy.
Tracking brain changes over time
The study was led by neuroscientists at the University of Oslo and involved an international team of researchers. They analysed brain scans from more than 4,700 adults between the ages of 17 and 95. None of the participants had Alzheimer’s disease or any other form of cognitive impairment.
Each participant underwent at least two magnetic resonance imaging (MRI) scans over an average follow-up period of three years. This allowed the researchers to track subtle changes in brain structure over time, including shifts in brain volume and cortical thickness.
Overall, the researchers found that male brains showed a greater reduction in volume and signs of decline in more brain regions than female brains. The contrast was especially pronounced in the postcentral cortex, a region responsible for processing touch, temperature, pain, and awareness of body position. In men, this area declined by an average of 2 per cent per year, compared with 1.2 per cent per year in women.
Men were also more likely to show thinning and deterioration in regions linked to visual processing, memory, learning, and movement. Women did show signs of decline, too, and in some cases more than men. For example, fluid-filled cavities in the brain known as ventricles expanded more rapidly in women, a recognised marker of brain tissue loss. Still, taken together, the researchers concluded that men’s brains appeared to age more quickly overall.
Rethinking Alzheimer’s risk
The findings challenge a popular theory that women’s higher Alzheimer’s risk stems from faster brain ageing. Prof Charles Marshall, a clinical neurologist at Queen Mary University of London who was not involved in the study, told BBC Science Focus magazine that the results offered strong evidence against one possible explanation for an increased risk of Alzheimer’s disease in women, which is that women’s brains age faster than men’s.
Marshall cautioned that brain ageing and Alzheimer’s are linked in complex ways. He explained that Alzheimer’s develops when proteins such as amyloid and tau accumulate in the brain. “The degree to which this decline happens affects how quickly someone develops symptoms when they have Alzheimer’s proteins in their brain,” he said. “This is a major reason why people show symptoms of Alzheimer’s disease more as they get older.”
Limits and alternative explanations
Not all experts believe the study settles the issue. Dr Jacqui Hanley, head of research at Alzheimer’s Research UK, said there were important limitations. “All participants were healthy, and the brain changes seen do not necessarily mean that they will go on to develop Alzheimer’s disease,” she told the magazine, noting that the study period was short compared with the decades over which dementia can develop. “Future studies need to monitor people for longer periods and see if the changes lead on to Alzheimer’s.”
Other research points to different explanations for women’s higher dementia risk. A recent mouse study led by scientists at the University of California, Los Angeles (UCLA), highlighted a gene called Kdm6a, which sits on the X chromosome and may drive inflammation in brain immune cells known as microglia. Because women have two X chromosomes, they carry two copies of this gene.
Prof Rhonda Voskuhl, the study’s lead author, suggested that heightened inflammation may be beneficial earlier in life, helping women fight infection while oestrogen keeps inflammation in check. After menopause, when oestrogen levels fall, this balance may shift. Voskuhl said the loss of oestrogen could “unleash the proinflammatory and neurodegenerative effects” of Kdm6a.
Supporting this idea, separate research has found that earlier menopause is associated with higher dementia risk, while hormone replacement therapy after menopause is linked to lower risk. Voskuhl said future treatments might aim to counter both inflammation and hormone loss. “This two-pronged approach to mitigate a sex chromosome effect and boost a sex hormone effect may be the ideal solution for women,” she told the magazine.
For now, the reasons behind women’s higher Alzheimer’s risk remain unresolved. But the new findings suggest that faster brain ageing in women is unlikely to be the full explanation, adding another layer to an already complex puzzle.
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