Title:Sex-based Disparities in Brain Aging: A Focus on Parkinson's Disease

Abstract:PD is linked to faster brain aging. Sex is recognized as an important factor in PD, such that males are twice as likely as females to have the disease and have more severe symptoms and a faster progression rate. Despite previous research, there remains a significant gap in understanding the function of sex in the process of brain aging in PD patients. The T1-weighted MRI-driven brain-predicted age difference was computed in a group of 373 PD patients from the PPMI database using a robust brain-age estimation framework that was trained on 949 healthy subjects. Linear regression models were used to investigate the association between brain-PAD and clinical variables in PD, stratified by sex. All female PD patients were used in the correlational analysis while the same number of males were selected based on propensity score matching method considering age, education level, age of symptom onset, and clinical symptom severity. Despite both patient groups being matched for demographics, motor and non-motor symptoms, it was observed that males with Parkinson's disease exhibited a significantly higher mean brain age-delta than their female counterparts . In the propensity score-matched PD male group, brain-PAD was found to be associated with a decline in general cognition, a worse degree of sleep behavior disorder, reduced visuospatial acuity, and caudate atrophy. Conversely, no significant links were observed between these factors and brain-PAD in the PD female group.