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Background and objectives: Alzheimer's disease (AD) is more prevalent in women than in men; however, there is a discrepancy in research on sex differences in AD. The human brain is a large-scale network with hub regions forming a central core, the rich-club, which is vital to cognitive functions. However, it is unknown whether alterations in the rich-clubs in AD differ between men and women. We aimed to investigate sex differences in the rich-club organization in the brains of patients with AD. Methods: In total, 260 cognitively unimpaired individuals with negative amyloid positron emission tomography (PET) scans, 281 with prodromal AD (mild cognitive impairment due to AD) and 285 with AD dementia who confirmed with positive amyloid PET scans participated in the study. We obtained high-resolution T1-weighted and diffusion tensor images and performed network analysis. Results: We observed sex differences in the rich-club and feeder connections in patients with AD, suggesting lower structural connectivity strength in women than in men. We observed a significant group-by-sex interaction in the feeder connections, particularly in the thalamus. In addition, the connectivity strength of the thalamus in the feeder connections was significantly correlated with general cognitive function in only men with prodromal AD and women with AD dementia. Conclusion: Our findings provide important evidence for sex-specific alterations in the structural brain network related to AD.
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OBJECTIVE: To investigate whether the presence of autonomic dysfunction is associated with white matter and functional connectivities and the level of cognitive performance in patients with de novo Parkinson disease (PD). METHODS: Seventy-five patients with de novo PD underwent a comprehensive autonomic function test and were classified into 2 groups according to the Composite Autonomic Severity Score (CASS; 30 with moderate to severe autonomic dysfunction [CASS 4-10, PD-AUT+] and 45 without significant autonomic dysfunction [CASS 0-3, PD-AUT-]). Network-based statistics and a graph theoretical analysis were performed to assess the interregional white matter connectivity using diffusion tensor imaging. We also performed analyses of resting-state functional connectivity and compared cognitive performance between the 2 groups. RESULTS: There were no significant differences in demographic characteristics and vascular risk factors between the PD-AUT+ and PD-AUT- groups. The PD-AUT+ group showed poorer cognitive performance on frontal/executive function than the PD-AUT- group. The PD-AUT+ group exhibited severely disrupted white matter connectivity in both fronto-subcortical and posterior cortical regions, which was well correlated with the severity of autonomic dysfunction assessed by the CASS. In addition, functional connectivity within the executive control network and dorsal attention network negatively correlated with the CASS. CONCLUSIONS: Our results suggest that autonomic dysfunction is associated with disrupted white matter and functional brain connectivity as well as cognitive impairment in de novo patients with PD.