Cerebrovascular disease is common in patients on the Lewy body (LB) continuum (dementia with Lewy bodies (DLB) and prodromal-DLB). White matter signal abnormality (WMSA) volume is higher in patients with LB than controls, both globally and in cholinergic white matter. However, it remains unknown if the higher WMSA in cholinergic white matter reflects selective cholinergic vulnerability or results from higher global WMSA. We modelled cingulate and external capsule cholinergic white matter pathways using MRI and segmented WMSA overlapping cholinergic pathways and per brain lobe. We found that patients on the LB-continuum (n = 33) had higher volume and proportion of WMSA in the cholinergic white matter compared to controls (n = 36), independent of global WMSA. Cholinergic WMSA was associated with neurodegeneration in the basal forebrain, decreased integrity of cingulate and external capsule pathways and attention and memory performance. These findings may suggest a selective vulnerability of cholinergic pathways in patients with LB.

Center of Biomedical Investigation Network for Neurodegenerative Diseases Madrid Spain

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway

Clinical Institute of Radiology University Medical Center Ljubljana Ljubljana Slovenia

Department of Biomedical Engineering and Assistive Technology Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Prague Czechia

Department of Neurology University Medical Centre Ljubljana Ljubljana Slovenia

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

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 España

Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Autònoma de Barcelona Barcelona Spain

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