Sleep and Sex: Why Women Are Better Protected Against Brain Atrophy Than Men

A study published in Nature Communications shows that women with isolated REM sleep behaviour disorder (iRBD) exhibit significantly less brain atrophy — a reduction in cortical thickness — compared to men, despite having comparable clinical symptoms.

iRBD is characterised by people essentially “acting out” their dreams: during REM sleep, they perform sudden and vigorous movements. This condition was long considered harmless, but it is now recognised as one of the most reliable early warning signs of neurodegenerative diseases such as Parkinson’s disease, Lewy body dementia, or multiple system atrophy.

This large international study involved nearly 700 participants. The researchers analysed 888 MRI scans collected from nine centres in Canada, the Czech Republic, the UK, France, Australia, Denmark, and Italy. After quality control, the final analysis included 687 participants — 343 with iRBD and 344 healthy controls.

The findings were striking: men with iRBD showed significant cortical atrophy in 37% of cortical regions, whereas women showed atrophy in only 1% of such regions. The average age of participants was about 67, and both men and women had similar clinical characteristics.

The scientists also discovered that the brain regions “protected” in women demonstrate increased expression of genes associated with estrogen receptors (such as ESRRG and ESRRA). These genes — particularly ESRRG — play a key role in mitochondrial function, energy production, and the survival of dopaminergic neurons, the very neurons that degenerate in Parkinson’s disease.

The authors of the study stress that identifying such protective mechanisms is important not only for understanding sex as a biological variable in clinical research, but also for paving the way toward personalised medicine, where treatment strategies can account for a patient’s sex and specific gene expression patterns.

The study shows that women with iRBD have a brain-protection advantage even in the early stages of neurodegeneration, and that understanding this phenomenon may be key to developing new therapies and to more precise approaches for preventing and treating REM sleep–related and neurodegenerative disorders.

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