Brain aging is a major risk factor for Alzheimer’s disease. 

A large new brain-imaging study indicates that men’s brains may undergo age-related decline faster than women’s, challenging long-held assumptions about why Alzheimer’s disease is more common in women.

The research, published in Proceedings of the National Academy of Sciences, examined patterns of brain ageing—a key risk factor for Alzheimer’s, the most prevalent form of dementia. Because women are diagnosed with Alzheimer’s nearly twice as often as men, many scientists have proposed that female brains might age more quickly. The new findings complicate that explanation.

How the study was conducted

An international team led by neuroscientists at the University of Oslo analyzed MRI scans from more than 4,700 healthy adults between the ages of 17 and 95. None of the participants had Alzheimer’s or any diagnosed cognitive impairment.

Each individual underwent at least two brain scans over an average follow-up period of about three years. This allowed researchers to track structural changes in the brain over time, including volume loss and thinning in specific regions.

Across the dataset, male brains showed steeper declines in overall brain volume and more widespread signs of deterioration compared with female brains. The differences were especially pronounced in the postcentral cortex—a region involved in processing touch, temperature, pain, and body awareness.

In this area, men experienced an average annual decline of around 2 percent, while women showed a decrease closer to 1.2 percent per year.

Men were also more likely to show age-related thinning in regions tied to vision, memory, learning, and movement. Women, however, were not entirely spared. In some brain areas, including the ventricles—fluid-filled spaces whose expansion signals tissue loss—women showed greater changes than men.

Taken together, the researchers concluded that, overall, male brains appear to age more rapidly.

What the findings suggest

The results may help rule out one popular explanation for women’s higher Alzheimer’s risk. Professor Charles Marshall, a clinical neurologist at Queen Mary University of London who was not involved in the study, described the findings as strong evidence against the idea that women develop Alzheimer’s more often because their brains age faster.

Marshall emphasized that brain ageing alone does not directly cause Alzheimer’s. Instead, the disease is driven by the accumulation of proteins such as amyloid and tau. Younger, healthier brains can better tolerate these changes, but as the brain shrinks and weakens with age, its resilience declines.

“The extent of brain decline influences how quickly symptoms appear once Alzheimer’s pathology is present,” Marshall explained. “That’s why the disease becomes more common with advancing age.”

Some earlier studies had suggested that women might experience this vulnerability sooner, but past research has produced mixed results. This new study challenges that hypothesis, though it does not definitively disprove it.

Dr Jacqui Hanley, head of research at Alzheimer’s Research UK, noted important limitations. The participants were all healthy, and the brain changes observed do not necessarily mean they will go on to develop dementia. She also pointed out that three years is a relatively short window for studying a disease that can take decades to emerge.

Longer-term studies, she said, will be needed to determine whether these structural changes are linked to future Alzheimer’s risk.

Other possible explanations

While the Norwegian study sheds light on brain ageing, it does not fully explain why women remain at higher risk for dementia. Other research points to biological differences beyond ageing itself.

One recent mouse study, published in Science Translational Medicine, identified a gene called Kdm6a as a potential contributor. Researchers at UCLA found that this gene may increase inflammation in microglia—the brain’s immune cells. Chronic inflammation is a known risk factor for Alzheimer’s and may interfere with the brain’s ability to clear toxic proteins such as tau.

Crucially, Kdm6a is located on the X chromosome. Women have two X chromosomes, while men have only one, meaning women carry two copies of the gene. In the study, deactivating Kdm6a in female mice reduced inflammatory signaling, whereas the same intervention had little effect in males.

Professor Rhonda Voskuhl, the study’s lead author, suggested that this heightened inflammatory response may be beneficial earlier in life, helping protect against infection during childbearing years. Oestrogen, which has anti-inflammatory and neuroprotective effects, likely keeps this response in check.

After menopause, however, declining oestrogen levels may allow inflammation linked to Kdm6a to intensify, potentially increasing the risk of neurodegeneration.

Supporting this idea, separate research from the University of Galway and Boston University found that earlier menopause was associated with a higher risk of dementia, while post-menopausal hormone replacement therapy was linked to a reduced risk.

Together, these findings suggest that women’s elevated Alzheimer’s risk may stem from a combination of genetic factors, inflammation, and hormonal changes rather than faster brain ageing alone.

Voskuhl has proposed that future treatments might aim to both counteract the effects of Kdm6a and address oestrogen loss after menopause. For now, however, much of this work remains based on animal models, and researchers continue to investigate the complex reasons behind women’s disproportionate risk of Alzheimer’s disease.

This article is for informational purposes only and is not medical advice.