BACKGROUND: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB. OBJECTIVES: We aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort. METHODS: 86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors. RESULTS: DLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker. CONCLUSIONS: This study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway; Department of Radiology Stavanger University Hospital Stavanger Norway; Department of Electrical Engineering and Computer Science University of Stavanger Stavanger Norway

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway; Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Neurology Charles University 2nd Medical Faculty and Motol University Hospital Prague Czech Republic; International Clinical Research Centre Brno Czech Republic

Department of Neurology University Medical Centre Ljubljana Medical faculty University of Ljubljana Ljubljana Slovenia

Department of Neuroscience Imaging and Clinical Sciences and CESI University G d'Annunzio of Chieti Pescara Chieti Italy

Department of Neuroscience Karolinska Institutet and Department of Radiology Karolinska University Hospital Stockholm Sweden

Division of Clinical Geriatrics Department of Neurobiology Care Sciences and Society Karolinska Institutet Stockholm Sweden

Division of Clinical Geriatrics Department of Neurobiology Care Sciences and Society Karolinska Institutet Stockholm Sweden; Department of Neuroimaging Centre for Neuroimaging Sciences Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Hôpitaux Universitaire de Strasbourg CMRR équipe IMIS Neurocrypto Strasbourg France

Hôpitaux Universitaire de Strasbourg Laboratoire de Biochimie et Biologie Moléculaire et CNRS Laboratoire de Neurosciences Cognitives et Adaptatives UMR7364 Strasbourg France

Movement Disorders Unit Neurology Department Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Barcelona Spain

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

Research Center and Memory Clinic Fundació ACE Institut Català de Neurociències Aplicades Universitat Internacional de Catalunya Barcelona Centro de Investigación en Red Enfermedades Neurodegenerativas Barcelona Spain

Research Center and Memory Clinic Fundació ACE Institut Català de Neurociències Aplicades Universitat Internacional de Catalunya Barcelona Centro de Investigación en Red Enfermedades Neurodegenerativas Barcelona Spain; Department of Medicine of the Universitat Autònoma de Barcelona Barcelona Spain

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Grey matter networks in women and men with dementia with Lewy bodies

Sex differences in brain atrophy in dementia with Lewy bodies

Sex differences in grey matter networks in dementia with Lewy bodies

MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies