December 2, 2025

Men and women who act out their dreams at night may not face the same risks for dementia later in life.

A new international study finds that men with REM sleep behavior disorder (RBD)—a sleep condition linked to vivid, physical dream enactment—show greater early brain shrinkage than women with the same disorder. Those brain changes appear in the same areas that later deteriorate in dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). The discovery suggests that women’s brains may have natural biological protections that slow or reduce the damage that can lead from RBD to dementia.

The connection between RBD and dementia

In healthy REM sleep, the brain turns off muscle activity so that dream content does not result in movement. In RBD, that “off switch” fails, and people may talk, punch, kick, or fall out of bed as they physically act out their dreams. On its own, RBD can be disruptive and even dangerous. But researchers have learned that it is also one of the earliest warning signs of certain brain diseases. More than 70% of people with RBD eventually develop a synucleinopathy—a disease marked by abnormal buildup of a protein called alpha-synuclein. The most common of these are Parkinson’s disease andDLB.

Because RBD can appear years or even decades before dementia symptoms start, it offers a unique window into the earliest stages of neurodegeneration.

A closer look at men’s and women’s brains

The new study, led by scientists at the University of Montreal and published in Nature Communications, analyzed brain MRI scans from 888 people—408 with confirmed RBD and 480 healthy controls, meaning people with no known major brain disorders. The researchers examined the cortex, which is the thin outer layer of the brain that supports thinking, voluntary movement, and sensation. When the cortex becomes thinner, that signals a loss of brain cells, a process that researchers call atrophy.

The results showed clear differences between the sexes:

• Men with RBD had much more cortical thinning than women, particularly in the back and top parts of the brain—regions that help with movement, coordination, and visual processing.
• Women had far less thinning, even though they were similar in age and disease severity.
• Among healthy volunteers, there were no meaningful sex differences, suggesting the gap appears only once the disease process begins.

In short, men’s brains showed more early damage, while women’s brains seemed to resist it.

Searching for the reason behind women’s resilience

To find out why, the team looked at gene activity patterns in healthy brain tissue and compared them with the brain regions that stayed intact in women with RBD. They discovered that these protected regions had higher expression of genes linked to estrogen-related receptors. One of the genes, ESRRG, was especially active in brain tissue compared to other organs, suggesting it plays a brain-specific protective role. This kind of molecular activity could help female brains withstand early damage from toxic proteins such as misfolded alpha-synuclein, which accumulate in Lewy body dementias.

What this means for dementia risk

The findings support the idea that sex-linked biological factors influence the path from RBD to dementia.

• For men, more widespread cortical thinning could indicate a faster or higher-risk trajectory toward diseases like DLB and PDD.
• For women, estrogen-related genetic activity may provide some protection, delaying or reducing early brain damage.

This does not mean women are immune—many still develop dementia—but understanding these differences may help doctors identify who is most at risk and why. It also highlights potential targets for future therapies that could strengthen the brain’s systems in both sexes.

Key takeaways for the public

• RBD is a powerful early warning sign for Lewy body–related dementias. Anyone who acts out dreams during sleep should be evaluated by a physician.
• Monitoring over time is key. Regular follow-up visits can help detect early cognitive or movement changes that suggest progression.
• Sex matters. Men and women may follow different paths from RBD toward dementia. Understanding these differences could lead to more personalized monitoring and treatment strategies.
• Research continues. Scientists are now studying whether targeting estrogen-related pathways could slow neurodegeneration.

Putting it all together

This large international study shows that men’s brains show earlier and more widespread atrophy in REM sleep behavior disorder, while women’s brains may benefit from protective, estrogen-related genes.

RBD remains one of the most important early clues to who may develop Lewy body–related dementia. By uncovering how sex differences shape that journey, researchers are getting closer to understanding why some brains are more resilient—and how that resilience might be shared with everyone.

REFERENCE:

Filiatrault, M., Ayral, V., Tremblay, C.et al. Estrogen-related receptor gene expression associates with sex differences in cortical atrophy in isolated REM sleep behavior disorder.Nat Commun16, 9016 (2025).https://doi.org/10.1038/s41467-025-63829-w