Sex differences permeate many aspects of dementia with Lewy bodies (DLB), yet sex differences in patterns of neurodegeneration in DLB remain largely unexplored. Here, we test whether grey matter networks differ between sexes in DLB and compare these findings to sex differences in healthy controls. In this cross-sectional study, we analysed clinical and neuroimaging data of patients with DLB and cognitively healthy controls matched for age and sex. Grey matter networks were constructed by pairwise correlations between 58 regional volumes after correction for age, intracranial volume, and centre. Network properties were compared between sexes and diagnostic groups. Additional analyses were conducted on w-scored data to identify DLB-specific sex differences. Data from 119 (68.7 ± 8.4 years) men and 45 women (69.9 ± 9.1 years) with DLB, and 164 healthy controls were included in this study. Networks of men had a lower nodal strength compared to women. In comparison to healthy women, the grey matter networks of healthy men showed a higher global efficiency, modularity, and fewer modules. None of the network measures showed significant sex differences in DLB. Comparing DLB patients with healthy controls revealed global differences in women and more local differences in men. Modular analyses showed a more distinct demarcation between cortical and subcortical regions in men compared with women. While topologies of grey matter networks differed between sexes in healthy controls, those sex differences were diluted in DLB patients. These findings suggest a disease-driven convergence of neurodegenerative patterns in women and men with DLB, which may inform precision medicine in DLB.

Center for Age Related Medicine Stavanger University Hospital Stavanger Norway

Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas Barcelona Catalonia Spain

Day Hospital of Geriatrics Memory Resource and Research Centre of Strasbourg Department of Geriatrics Hopitaux Universitaires de Strasbourg Strasbourg France

Department of Electrical Engineering and Computer Science University of Stavanger Stavanger Norway

Department of Neuroimaging Centre for Neuroimaging Sciences Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Neurology and Alzheimer Center VU University Medical Center Amsterdam Netherlands

Department of Neurology Mayo Clinic Rochester MN USA

Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Radiology Mayo Clinic Rochester MN USA

Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institute Stockholm Sweden

Facultad de Ciencias de la Salud Universidad Fernando Pessoa Canarias Las Palmas Spain

ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg ICONE Strasbourg France

Institute of Biomedical Research August Pi i Sunyer Barcelona Spain

Medical Psychology Unit Department of Medicine Institute of Neurosciences University of Barcelona Barcelona Spain

Memory Clinic Department of Neurology 2nd Faculty of Medicine Charles University Prague Czech Republic

Motol University Hospital Prague Czech Republic

Quantitative Health Sciences Mayo Clinic Rochester MN USA

University Hospital of Psychiatry and Psychotherapy Bern University of Bern Bern Switzerland

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Res Sq. 2023 Jan 30:rs.3.rs-2519935. doi: 10.21203/rs.3.rs-2519935/v1. PubMed

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