Differences in brain aging between sexes in Parkinson's disease

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Parkinson's disease (PD) is associated with accelerated brain aging, with males exhibiting higher prevalence and more severe symptoms.
• The role of sex in brain aging within Parkinson's disease remains under-investigated, highlighting a critical knowledge gap.

Purpose of the Study:

• To investigate the association between sex and brain-predicted age difference (Brain-PAD) in individuals with Parkinson's disease.
• To explore the relationship between Brain-PAD and clinical variables, stratified by sex, in Parkinson's disease patients.

Main Methods:

• Brain-predicted age difference (Brain-PAD) was calculated using structural T1-weighted MRI data from 373 Parkinson's disease patients.
• A robust brain-age estimation framework trained on 949 healthy subjects was employed.
• Linear regression models analyzed the association between Brain-PAD and clinical variables (cognition, sleep, visuospatial acuity, caudate atrophy), stratified by sex.

Main Results:

• Males with Parkinson's disease (PD-M) demonstrated a significantly higher mean Brain-PAD than females with Parkinson's disease (PD-F).
• In propensity score-matched PD-M, higher Brain-PAD correlated with general cognitive decline, worse sleep behavior disorder, reduced visuospatial acuity, and caudate atrophy.
• No significant associations between Brain-PAD and these clinical factors were found in the PD-F group.

Conclusions:

• Accelerated brain aging in males with Parkinson's disease suggests a vital role for sex in PD pathogenesis.
• The findings indicate potentially distinct mechanisms of Parkinson's disease in males and females.
• This study enhances understanding of sex-based differences in brain aging within the context of Parkinson's disease.