Objective: To investigate sex-related differences of resting-state functional magnetic resonance imaging (rs-fMRI) metrics in early-stage, untreated Parkinson’s disease (PD) patients.

Background: Sex plays an important role in the heterogeneity of PD, but its effects on resting-state brain activity in PD remain unclear.

Method: Three hundred and six PD patients (207 males and 99 females) and 242 controls (107 males and 135 females) were included based on the availability of T1-weighted magnetic resonance imaging (MRI) and rs-fMRI. We first generated three diverse rs-fMRI metrics for both PD patients and healthy controls (HC), specifically regional homogeneity (ReHo) map, amplitude of low-frequency fluctuation (ALFF) map, and functional connectivity (FC) matrices. Then, we performed voxel-wise analysis to examine differences of whole-brain ReHo and ALFF between PD patients and HCs across sexes, and region-to-region level analysis to explore potential sex-related differences in FC between brain regions in PD.

Results: Primarily, ReHo differences between PD patients and HCs varied in males and females, while ALFF differences driven by PD compared to HCs remained consistent across sexes. Additionally, region-to-region FC analysis revealed higher FC of multiple regional pairs in male PD patients compared to females, while no sex-related differences were observed in HCs. Moreover, in contrast to the predominantly positive within-network FC observed in male PD patients and all HCs, female PD patients exhibited significant between-network negative FC. This was particularly evident within the default mode network (DMN) and somatomotor network (SMN), as well as between the DMN and ventral attention network (VAN). Lastly, we found sex-related differences in the correlation between rs-fMRI metrics and the severity of non-motor symptoms in PD.

Conclusion: Our study highlights significant sex-related differences of brain function and non-motor symptoms in PD, underlining the importance of considering sex in PD research and treatment approaches.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-related-differences-of-resting-state-brain-activity-in-parkinsons-disease/