Sex Differences in Brain Structure in De Novo Parkinson's Disease: A Cross-Sectional and Longitudinal Neuroimaging Study

Background: Parkinson's disease (PD) varies in occurrence, presentation, and severity between males and females. However, the sex effects on the patterns of brain structure, cross-sectionally and longitudinally, are still unclear.

Objective: We aimed to compare sex differences in brain features cross-sectionally and longitudinally using grey matter volume (GMV) and cortical thickness in a large sample of newly diagnosed drug-naive PD patients.

Methods: Cognitive assessments and structural MR images of 262 PD patients (171 males) and 113 healthy controls (68 males) were selected from the Parkinson's Progression Markers Initiative. Of these, 97 PD patients (66 males) completed 12- and 24-month follow-up examinations. After regressing out the expected effects of age and sex, brain maps of GMV and cortical thickness were compared using two-sample t tests cross-sectionally and were compared using repeated measurement analyses of variance longitudinally.

Results: At baseline, male PD patients exhibited a greater extent of brain atrophy and cortical thickness reduction than females, which mainly occurred in the cerebellum, frontal lobe, parietal lobe, and temporal lobe. At follow-up, female and male PD patients showed similar dynamics of disease progression, as both groups declined over time while the females maintained the advantage. The cortical thickness of the right precentral gyrus at baseline was negatively associated with the longitudinal changes of motor function in male PD patients.

Conclusion: The current findings might demonstrate sex effect in neuroanatomy during the course of PD, provide new insights into the neurodegenerative process, and facilitate the development of more effective sex-specific therapeutic strategies.