Women Show Better Brain Protection Against Early Neurodegeneration in Parkinson's Disease

Strategic Insights -

A groundbreaking international study has found that women with a precursor condition to Parkinson's disease, known as isolated REM sleep behavior disorder, exhibit significantly less brain atrophy than men, despite similar clinical severity. The research, involving nearly 700 participants from nine international centers, reveals that women show remarkable brain protection, with only 1% of cortical regions affected, compared to 37% in men. This protective phenomenon may be linked to the action of estrogens and estrogen-related receptors in the brain, which play a crucial role in mitochondrial function, cellular energy production, and the survival of dopamine-producing neurons.

Key Takeaways:

  • Women with isolated REM sleep behavior disorder show significantly less brain atrophy than men, with 1% of cortical regions affected compared to 37% in men.
  • The study involved nearly 700 participants from nine international centers, including the University of Montreal, the Czech Republic, the United Kingdom, France, Australia, Denmark, and Italy.
  • The research team used an innovative approach to compare brain images with gene presence in different brain regions, measured in healthy brains studied after death, revealing increased expression of estrogen-related hormone receptors in brain regions less affected in women.
  • The ESRRG and ESRRA genes, which produce estrogen-related hormone receptors, play a crucial role in mitochondrial function, cellular energy production, and the survival of dopamine-producing neurons.
  • The study's findings suggest that estrogen-related receptors may be a promising therapeutic target for the treatment of Parkinson's disease.
  • The researchers recommend considering sex as a biological variable in clinical trials, which could increase statistical power and reduce the number of participants needed.
  • Longitudinal data currently being collected will enable better understanding of how these sex differences influence progression to manifest neurodegenerative diseases.

Statistics:

  • 87% of cortical areas showed significant atrophy in men with isolated REM sleep behavior disorder.
  • 1% of regions were affected in women with isolated REM sleep behavior disorder.
  • 343 patients with isolated REM sleep behavior disorder and 344 healthy individuals were included in the final analysis.
  • The study involved 687 participants, with a mean age of around 67 years.
  • The brain regions less affected in women showed increased expression of genes associated with estrogen function, notably the ESRRG and ESRRA genes.

Sources:

  • "Estrogen-related receptor gene expression associates with sex differences in cortical atrophy in isolated REM sleep behavior disorder" by Marie Filiatrault and collaborators, published in Nature Communications on October 10, 2025.
  • Alzheimer Society of Canada
  • Parkinson Canada