Parkinson’s disease (PD) is linked to faster brain aging. Male sex is associated with higher prevalence, severe symptoms, and a faster progression rate in PD. There remains a significant gap in understanding the function of sex in the process of brain aging in PD. The structural T1-weighted MRI-driven brain-predicted age difference (i.e., Brain-PAD: the actual age subtracted from the brain-predicted age) was computed in a group of 373 people with PD (mean age ± SD: 61.37 ± 9.81, age range: 33–85, 34% female) from the Parkinson’s Progression Marker Initiative 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. Males with Parkinson’s disease (PD-M) exhibited a significantly higher mean Brain-PAD than their female counterparts (PD-F) (t(256) = 2.50, p = 0.012). In the propensity score-matched PD-M group (PD-M*), 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-F group. Having ‘older’ looking brains in PD-M than PD-F supports the idea that sex plays a vital function in PD, such that the PD mechanism may be different in males and females. This study has the potential to broaden our understanding of dissimilarities in brain aging between sexes in the context of PD.

帕金森病 (PD) 与大脑加速老化有关。男性与帕金森病的患病率较高、症状严重和进展速度较快有关。对于性在帕金森病大脑衰老过程中的作用的理解仍然存在很大差距。在 373 名 PD 患者中计算了结构 T1 加权 MRI 驱动的大脑预测年龄差异（即 Brain-PAD：从大脑预测年龄中减去实际年龄）（平均年龄 ± SD：61.37 ± 9.81 ，年龄范围：33-85 岁，34% 女性）来自帕金森病进展标记计划数据库，使用强大的大脑年龄估计框架，该框架在 949 名健康受试者身上进行了培训。使用线性回归模型研究 Brain-PAD 与 PD 临床变量之间的关联，按性别分层。帕金森病男性 (PD-M) 的平均 Brain-PAD 显着高于女性患者 (PD-F)（t (256) = 2.50，p  = 0.012）。在倾向评分匹配的 PD-M 组 (PD-M*) 中，发现 Brain-PAD 与一般认知能力下降、睡眠行为障碍程度更严重、视觉空间敏锐度降低和尾状核萎缩有关。相反，在 PD-F 组中，这些因素与 Brain-PAD 之间没有观察到显着的联系。 PD-M 患者的大脑比 PD-F 患者的大脑看起来“更老”，这支持了性别在 PD 中发挥重要作用的观点，因此男性和女性的 PD 机制可能不同。这项研究有可能扩大我们对帕金森病背景下两性大脑衰老差异的理解。