Sex-Specific Imaging Biomarkers for Parkinson’s Disease Diagnosis: A Machine Learning Analysis

Abstract

This study aimed to identify sex-specific imaging biomarkers for Parkinson’s disease (PD) based on multiple MRI morphological features by using machine learning methods. Participants were categorized into female and male subgroups, and various structural morphological features were extracted. An ensemble Lasso (EnLasso) method was employed to identify a stable optimal feature subset for each sex-based subgroup. Eight typical classifiers were adopted to construct classification models for PD and HC, respectively, to validate whether models specific to sex subgroups could bolster the precision of PD identification. Finally, statistical analysis and correlation tests were carried out on significant brain region features to identify potential sex-specific imaging biomarkers. The best model (MLP) based on the female subgroup and male subgroup achieved average classification accuracy of 92.83% and 92.11%, respectively, which were better than that of the model based on the overall samples (86.88%) and the overall model incorporating gender factor (87.52%). In addition, the most discriminative feature of PD among males was the lh 6r (FD), but among females, it was the lh PreS (GI). The findings indicate that the sex-specific PD diagnosis model yields a significantly higher classification performance compared to previous models that included all participants. Additionally, the male subgroup exhibited a greater number of brain region changes than the female subgroup, suggesting sex-specific differences in PD risk markers. This study underscore the importance of stratifying data by sex and offer insights into sex-specific variations in PD phenotypes, which could aid in the development of precise and personalized diagnostic approaches in the early stages of the disease.