Men’s brains appear to age more quickly than women’s, according to a recent study published in Proceedings of the National Academy of Sciences.
Brain ageing is a major risk factor for Alzheimer’s, the most common form of dementia, leading some scientists to suggest that different brain ageing speeds might explain why women are nearly twice as likely to develop the disease than men.
Yet this research has suggested that, in fact, male brains might age more quickly than female brains, throwing into question why women have such a high Alzheimer’s risk.
What the scientists did
In this study, an international team of scientists led by neuroscientists at the University of Oslo, Norway analysed brain scans from more than 4,700 adults, aged 17 to 95 years.
Overall, they found that male brains showed a greater reduction in brain volume and signs of decline in more regions of the brain compared to female brains. This suggests that male brains may deteriorate more rapidly with age.
None of the participants had Alzheimer’s or any other form of cognitive impairment, and they were only followed for an average of three years, which is relatively short for this type of brain ageing study.
During the study, each participant had at least two scans taken of their brain using magnetic resonance imaging (MRI) so the scientists could compare how the participants’ brains changed over time.
The difference was most stark in the postcentral cortex, which processes sensations of touch, temperature, pain, and the body’s awareness of its own positioning.
This area declined by an average of 2 per cent per year among men, but only 1.2 per cent per year among women.
Men were also more likely to show signs of thinning and deterioration in other brain regions, including those associated with visual processing, memory, learning and movement.
Meanwhile, women did show signs of brain decline – in some areas, more than men. For instance, fluid-filled cavities called ventricles were more likely to expand over time in female brains, which is a sign of brain tissue loss.
But overall, the scientists concluded that men’s brains seemed to be ageing more quickly.
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What this means
The findings of this study might help scientists understand why women are more likely to develop Alzheimer’s than men – a mystery that remains to be solved.
Prof Charles Marshall – a clinical neurologist at Queen Mary University of London, who was not involved in this study – told BBC Science Focus that this study served as “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 explained that the relationship between brain ageing and Alzheimer’s was not straightforward. In other words, ageing didn’t directly cause the other.
Instead, he said, the disease developed when proteins called amyloid and tau built up in the brain. Our brains could resist the negative effects of these proteins while healthy and young, Marshall explained, but this becomes more difficult when age makes our brains shrink and decline.
“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.”
Some scientists have suggested that female brains may experience this decline earlier than men, to explain why they were more likely to develop dementia.
But earlier studies came to mixed conclusions – and this one seems to overturn the idea that women’s brains age more quickly.
That’s not to say that this study has totally disproven that idea. Dr Jacqui Hanley – the head of research at Alzheimer’s Research UK, who also did not take part in this study – told BBC Science Focus that there were some key limitations to this research.
“All participants were healthy, and the brain changes seen do not necessarily mean that they will go on to develop Alzheimer’s disease,” she said, noting that this was a relatively short study compared to the timespan in which Alzheimer’s could develop – sometimes decades.
“Future studies need to monitor people for longer periods and see if the changes lead on to Alzheimer’s,” said Hanley.
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An alternative explanation
While the Norwegian study couldn’t explain why women were more likely to develop dementia than men, other recent studies have suggested alternative explanations.
Notably, a mouse study published in Science Translational Medicine has pointed to a gene that might be to blame.
Scientists at the University of California, Los Angeles (UCLA) concluded that a gene called Kdm6a might drive inflammation in brain immune cells, known as microglia.
Inflammation, like ageing, is a key risk factor for Alzheimer’s – but Kdm6a might, perhaps, block microglia from being able to clear away harmful proteins in the brain, like tau, allowing them to accumulate and cause damage.
The crux is that Kdm6a lives on the X chromosome. Men only have one X chromosome, whereas women have two – meaning they have two copies of this gene and might be doubly affected by it.
In fact, when the UCLA scientists tried deactivating Kdm6a in female mice, it also deactivated some inflammatory molecules in their brains.
However, when they tried the same thing in male mice, the effect was almost undetectable.
Prof Rhonda Voskuhl, the study’s lead author and a neurologist at UCLA, said in a statement that this heightened inflammation might be useful earlier in a woman’s life.
She said that, at childbearing age, extra inflammation might help female bodies ward off infection, while being kept in check by oestrogen – a female sex hormone with anti-inflammatory and brain-protective properties.
But, when women reach menopause, their oestrogen levels drop, which Voskuhl said may "unleash the proinflammatory and neurodegenerative effects" of Kdm6a.
The link between oestrogen exposure and Alzheimer’s risk was further cemented by another recent study, this time by the University of Galway and Boston University.
This time, scientists found that entering menopause at an earlier age was associated with an increased risk of dementia.
Meanwhile, using hormone replacement therapy (HRT) after menopause – in other words, supplementing oestrogen – was associated with a lower dementia risk.
So, women’s heightened dementia risk might be linked to elevated levels of inflammation in their brains, caused by duplicated Kdm6a genes and a loss of oestrogen after menopause.
Voskuhl told BBC Science Focus that, in future, menopausal women might be able to reduce their Alzheimer’s risk with treatments counterbalancing the effects of Kdm6a and oestrogen 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 said.
However, her study was only on mice – for now at least, the mystery behind women's heightened Alzheimer's risk is one scientists are continuing to unlock.
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