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

Abstract

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 T1-weighted 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.

Results: 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.

Keywords: Parkinson's disease; cortical surface; morphological brain network; rapid eye movement sleep behavior disorder; sex differences.

Figure 1

Brain regions showing intragroup differences between males and females analyzed by VBM. (A) Shows the findings for the HC group, and (B, C) show the findings for the PD-pRBD groups. The red area represents a higher GMV in females than in males. M, male; F, female.

Figure 2

Brain regions showing intragroup differences in cortical morphological indicators between males and females in SBM analyses, (A) indicates differences in cortical morphometric indices between male and female healthy controls, (B) indicates sex differences in the PDnon-pRBD group, and (C) indicates sex differences in the PD-pRBD group. Negative values indicate that the indices for males were higher than those for females, and positive values indicate that the indices for males were lower than those for females (few-corrected, P < 0.001 for vertex, P < 0.05 for cluster). M, male; F, female.

Figure 3

Topological characterization of the network. (A–C) Represent global brain network properties, (A) shows the findings for the PD-pRBD group, while (B, C) show the findings for the PDnon-pRBD group, (D–F) represent nodal brain network properties. (D) Shows the findings for the PD-pRBD group; (E) shows the findings for the PDnon-pRBD group, and (F) shows the findings for the HC group. *Denotes P < 0.05 and ** denotes P < 0.01. M, male; F, female. Eg, Global efficiency; Cp, Clustering coefficient; Eloc, Local efficiency; Lp, Characteristic path length; γ, Normalized clustering coefficient; σ, Small world; Ne, Nodal efficiency; Dc, Degree centrality; Bc, Betweenness centrality.

Figure 4

Relationships between network properties and clinical variables. The correlation between the Delayed Recall of HVLT-R with global brain network properties in PD-pRBD patients is illustrated in the figure. The Delayed Recall score of HVLT-R is positively correlated with Eloc, Cp, Eg, γ, and σ, and negatively correlated with the Lp.