A new large-scale international study published in Nature Communications revealed a significant difference in the brains of men and women with a precursor condition of Parkinson’s disease. It was found that women exhibit a considerably lower degree of brain atrophy, despite similar clinical severity of the disease.
The study focused on isolated REM sleep behavior disorder (iRBD), a condition in which people physically act out their dreams during sleep. This condition (iRBD) is fundamentally different from typical sleep movement (such as twitching). In iRBD, muscle paralysis does not occur during the REM sleep phase, causing patients to physically act out the content of their dreams, which often manifests as violent or vigorous movements. This behavior can lead to injury for both the patient and their bed partner.
iRBD is linked to a dysregulation of dopamine release in the central nervous system. This dysfunction is considered a factor in the development of Parkinson’s disease (PD).
More than 70% of patients with iRBD eventually develop neurodegenerative diseases such as Parkinson’s, Dementia with Lewy Bodies, or Multiple System Atrophy. Therefore, the study of iRBD provides a unique opportunity to investigate the mechanisms of neurodegeneration.
The researchers analyzed brain data from 687 participants across nine international centers. The results were striking: atrophy was observed in 37% of cortical regions in men with iRBD, while this figure was only 1% in women. Men exhibited more widespread and severe cortical thinning, particularly in areas responsible for controlling movement, sensation, vision, and spatial orientation.
To understand this protective phenomenon observed in women, the scientists used an innovative approach: they compared the results of brain scans with which genes were active in different parts of the brain. The analysis showed an increased expression of genes related to estrogen function, specifically the ESRRG and ESRRA genes, in the less affected brain regions of women.
These genes produce estrogen-related hormone receptors that play a crucial role in mitochondrial function, cellular energy production, and the preservation of dopamine-producing neurons—the very neurons destroyed in Parkinson’s disease.
The study’s findings are significant because, as it turned out, certain areas of the female brain are better protected, likely through the action of estrogens and associated energy processes. The study results underscore the necessity of considering sex as a biological variable in clinical research.
