Sex-specific brain morphological and network differences in patients showing Parkinson's disease with and without possible rapid eye movement sleep behavior disorder

Yang Liu ¹ Pengfei Zhang ¹ Hao Li ¹ Liang Zhou ¹ Jingqi Jiang ¹ Yanli Jiang ¹ Kai Ai ² Guangyao Liu ¹ Jing Zhang ^1*

• ¹ Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
• ² Department of Clinical and Technical Support, Philips Healthcare, Xi’an, China

Background: Sex is a crucial determinant in the clinical manifestations of diseases. However, previous studies have not clarified whether altered brain morphology shows sex-specific patterns in patients with Parkinson's disease (PD) with or without possible rapid eye movement sleep behavior disorder (RBD). This study aimed to investigate sex-specific differences in the patterns of morphological changes among different subgroups of PD. Methods: High-resolution T1weighted magnetic resonance imaging and clinical scale data were collected from 278 participants in the Parkinson's disease Progression Marker Initiative database: 93 patients with PD-pRBD (60 males, 33 females), 114 patients showing PD without RBD (PDnon-pRBD group; 68 males, 46 females), and 71 healthy controls (HCs; 44 males, 17 females). The Computational Anatomy Toolbox (CAT) 12 was utilized to collect data on gray matter volume (GMV) and cortical morphological metrics. Subsequently, individual-level morphological similarity networks were constructed on the basis of these cortical metrics. Finally, the topological properties of the network were analyzed using graph theoretical methods.In the PD-pRBD group, the GMV in the frontal and temporal lobes of males was lower than that of females. In contrast, the gyrification index (GI) of the frontal lobe in males was lower than that in females within the PDnon-pRBD group. Network analyses based on graph theory revealed that male PD-pRBD patients showed lower network information integration than female patients, particularly in terms of the global properties of fractal dimension (FD) networks.Moreover, in the PD-pRBD group, male patients showed a strong correlation between morphological network metrics and cognitive performance, as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) memory scores. Conclusion:The presence of more significant sex-related differences in brain morphological changes in the PD-pRBD group in comparison with the PDnon-pRBD group highlights the importance of considering sex-related differences in the diagnosis and management of patients with PD-pRBD.