INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

Alzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam Amsterdam UMC location Vumc Amsterdam The Netherlands

Amsterdam Neuroscience Neurodegeneration Vrije Universiteit Amsterdam Amsterdam UMC location Vumc Amsterdam The Netherlands

Brain and Mind Research Central European Institute of Technology Masaryk University Brno Czech Republic

Center for Age Related Medicine Stavanger University Hospital Stavanger Norway

Department of Medicine and Aging Sciences University G d'Annunzio of Chieti Pescara Chieti Chieti Italy

Department of Neurology Mayo Clinic Rochester USA

Department of Neurology University Medical Center Ljubljana Slovenia

Department of Neuroscience Rehabilitation Ophthalmology Genetics Maternal and Child Health University of Genova Genova Italy

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

Department of Quality and Health Technology Faculty of Health Sciences University of Stavanger Stavanger Norway

Department of Quantitative Health Sciences Mayo Clinic Rochester Minnesota USA

Department of Radiology and Nuclear Medicine Amsterdam UMC Vrije Universiteit Amsterdam the Netherlands

Department of Radiology Mayo Clinic Rochester Minnesota USA

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

Division of Psychiatry University College London London UK

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

Geriatrics and Neurology Units Research and Resources Memory Center Hôpitaux Universitaires de Strasbourg Strasbourg France

ICube Laboratory Strasbourg France

Institute of Biomedical Research August Pi i Sunyer Barcelona Catalonia Spain

Medical Psychology Unit Department of Medicine Institute of Neuroscience University of Barcelona Barcelona Catalonia Spain

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

Memory Clinic Landspitali Reykjavik Iceland

Network Center for Biomedical Research in Neurodegenerative Diseases Barcelona Catalonia Spain

Neurology Unit Department of Clinical and Experimental Sciences University of Brescia Brescia Italy

Parkinson and Movement Disorders Unit Study Center on Neurodegeneration Padova Italy

Queen Square Institute of Neurology and Centre for Medical Image Computing University College London London UK

St Margaret's Hospital Essex Partnership University NHS Foundation Trust Essex UK

Stavanger Medical Imaging Laboratory Department of Radiology Stavanger University Hospital Stavanger Norway

The Norwegian Centre for Movement Disorders Stavanger University Hospital Stavanger Norway

Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK

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

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$a Sex differences in brain atrophy in dementia with Lewy bodies / $c J. Oltra, A. Habich, CG. Schwarz, Z. Nedelska, SA. Przybelski, A. Inguanzo, P. Diaz-Galvan, VJ. Lowe, K. Oppedal, MC. Gonzalez, N. Philippi, F. Blanc, F. Barkhof, AW. Lemstra, J. Hort, A. Padovani, I. Rektorova, L. Bonanni, F. Massa, MG. Kramberger, JP. Taylor, JG. Snaedal, Z. Walker, A. Antonini, T. Dierks, B. Segura, C. Junque, E. Westman, BF. Boeve, D. Aarsland, K. Kantarci, D. Ferreira

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$a INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

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