Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum

Abstract 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 un...

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Main Authors: Anna Rennie, Milan Nemy, Cene Jerele, Iñigo Rodríguez-Baz, Victor Montal, Alexandre Bejanin, Milica G Kramberger, Dag Aarsland, Juan Fortea, Alberto Lleó, Eric Westman, Daniel Alcolea, Daniel Ferreira
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01118-5
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author Anna Rennie
Milan Nemy
Cene Jerele
Iñigo Rodríguez-Baz
Victor Montal
Alexandre Bejanin
Milica G Kramberger
Dag Aarsland
Juan Fortea
Alberto Lleó
Eric Westman
Daniel Alcolea
Daniel Ferreira
author_facet Anna Rennie
Milan Nemy
Cene Jerele
Iñigo Rodríguez-Baz
Victor Montal
Alexandre Bejanin
Milica G Kramberger
Dag Aarsland
Juan Fortea
Alberto Lleó
Eric Westman
Daniel Alcolea
Daniel Ferreira
author_sort Anna Rennie
collection DOAJ
description Abstract 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.
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series npj Parkinson's Disease
spelling doaj-art-e61c9cc2584b40e3a63151224ab413862025-08-24T11:14:46ZengNature Portfolionpj Parkinson's Disease2373-80572025-08-0111111010.1038/s41531-025-01118-5Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuumAnna Rennie0Milan Nemy1Cene Jerele2Iñigo Rodríguez-Baz3Victor Montal4Alexandre Bejanin5Milica G Kramberger6Dag Aarsland7Juan Fortea8Alberto Lleó9Eric Westman10Daniel Alcolea11Daniel Ferreira12Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteDepartment of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de BarcelonaDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska InstituteAbstract 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.https://doi.org/10.1038/s41531-025-01118-5
spellingShingle Anna Rennie
Milan Nemy
Cene Jerele
Iñigo Rodríguez-Baz
Victor Montal
Alexandre Bejanin
Milica G Kramberger
Dag Aarsland
Juan Fortea
Alberto Lleó
Eric Westman
Daniel Alcolea
Daniel Ferreira
Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
npj Parkinson's Disease
title Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
title_full Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
title_fullStr Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
title_full_unstemmed Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
title_short Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
title_sort regional associations between cerebrovascular disease and cholinergic white matter pathways in the lewy body continuum
url https://doi.org/10.1038/s41531-025-01118-5
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