Regional associations between cerebrovascular disease and cholinergic white matter pathways in the Lewy body continuum
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.
Authors
- Juan Fortea (ORCID: https://orcid.org/0000-0002-1340-638X)
- Anna Rennie (ORCID: https://orcid.org/0000-0002-0976-8062)
- Íñigo Rodríguez‐Baz (ORCID: https://orcid.org/0000-0003-3039-9115)
- Víctor Montal (ORCID: https://orcid.org/0000-0002-5714-9282)
- Daniel Ferreira (ORCID: https://orcid.org/0000-0001-9522-4338)
- Cene Jerele (ORCID: https://orcid.org/0000-0002-5046-0481)
- Dag Aarsland (ORCID: https://orcid.org/0000-0001-6314-216X)
- Milan Němý (ORCID: https://orcid.org/0000-0002-4870-1354)
- Eric Westman (ORCID: https://orcid.org/0000-0002-3115-2977)
- Milica Gregorič Kramberger (ORCID: https://orcid.org/0000-0001-8231-1176)
- Alexandre Bejanin (ORCID: https://orcid.org/0000-0002-9958-0951)
- Daniel Andres Alcolea (ORCID: https://orcid.org/0000-0002-3819-3245)
- Alberto Lleó
Institutions
- Universitat Autònoma de Barcelona (ES)
- King's College London (GB)
- Stavanger University Hospital (NO)
- Ljubljana University Medical Centre (SI)
- Hospital de Sant Pau (ES)
- Karolinska Institutet (SE)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Universidad Fernando Pessoa Canarias (ES)
- Czech Technical University in Prague (CZ)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-08-21
- DOI
- https://doi.org/10.1038/s41531-025-01118-5
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alzheimer's Association
- České Vysoké Učení Technické v Praze
- Parkinson's Foundation
- European Commission
- Fondation Jérôme Lejeune
- Grantová Agentura České Republiky
- Generalitat de Catalunya
- Hjärnfonden
- Karolinska Institutet
- Stockholms Läns Landsting
- Vetenskapsrådet
- Alzheimerfonden
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Demensfonden
- National Institutes of Health
- Parkinsonfonden
- Instituto de Salud Carlos III
- European Regional Development Fund
- Center for Innovative Medicine
- National Institute on Aging