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Free water imaging of the cholinergic system in dementia with Lewy bodies and Alzheimer's disease

Lookup NU author(s): Julia SchumacherORCiD, Dr Calum Hamilton, Dr Paul Donaghy, Dr Michael FirbankORCiD, Dr Gemma Roberts, Dr Louise Allan, Nicola Barnett, Professor John O'Brien, Professor Alan ThomasORCiD, Professor John-Paul TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Degeneration of cortical cholinergic projections from the nucleus basalis of Meynert (NBM) is characteristic of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), whereas involvement of cholinergic projections from the pedunculopontine nucleus (PPN) to the thalamus is less clear. METHODS: We studied both cholinergic projection systems using a free water-corrected diffusion tensor imaging (DTI) model in the following cases: 46 AD, 48 DLB, 35 mild cognitive impairment (MCI) with AD, 38 MCI with Lewy bodies, and 71 controls. RESULTS: Free water in the NBM-cortical pathway was increased in both dementia and MCI groups compared to controls and associated with cognition. Free water along the PPN-thalamus tract was increased only in DLB and related to visual hallucinations. Results were largely replicated in an independent cohort. DISCUSSION: While NBM-cortical projections degenerate early in AD and DLB, the thalamic cholinergic input from the PPN appears to be more selectively affected in DLB and might associate with visual hallucinations. Highlights: Free water in the NBM-cortical cholinergic pathways is increased in AD and DLB. NBM-cortical pathway integrity is related to overall cognitive performance. Free water in the PPN-thalamus cholinergic pathway is only increased in DLB, not AD. PPN-thalamus pathway integrity might be related to visual hallucinations in DLB.

Publication metadata

Author(s): Schumacher J, Ray NJ, Hamilton CA, Bergamino M, Donaghy PC, Firbank M, Watson R, Roberts G, Allan L, Barnett N, O'Brien JT, Thomas AJ, Taylor J-P

Publication type: Article

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2023

Volume: 19

Issue: 10

Pages: 4549-4563

Print publication date: 01/10/2023

Online publication date: 15/03/2023

Acceptance date: 15/02/2023

Date deposited: 04/04/2023

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: John Wiley and Sons Inc


DOI: 10.1002/alz.13034

PubMed id: 36919460


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Funder referenceFunder name
ARUK-PG2015-13Alzheimer`s Research UK