Validation Of Cholinergic White Matter Biomarkers In Alzheimer's Disease And Dementia With Lewy Bodies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68407700%3A21730%2F25%3A00387997" target="_blank" >RIV/68407700:21730/25:00387997 - isvavai.cz</a>

Result on the web

<a href="https://cslide.ctimeetingtech.com/adpd25/attendee/confcal/show/session/106" target="_blank" >https://cslide.ctimeetingtech.com/adpd25/attendee/confcal/show/session/106</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Validation Of Cholinergic White Matter Biomarkers In Alzheimer's Disease And Dementia With Lewy Bodies

Original language description

Aims The cholinergic nucleus basalis of Meynert and its white matter projections are vulnerable in neurodegenerative diseases such as Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Here, we present cross-sectional and longitudinal results detailing microstructural alterations in cholinergic pathways across AD and DLB. Additionally, we introduce imaging-pathologic validation using post-mortem MRI of autopsy-confirmed AD and DLB cases to validate our in vivo biomarkers. Methods We evaluated participants including individuals with AD (n=33), mild cognitive impairment (MCI, n=58), subjective cognitive decline (SCD, n=178), and healthy controls (n=106) from the DELCODE study over up to 4 years with annual visits, and DLB patients (n=41) from the SPIN cohort. Using advanced diffusion imaging, integrating probabilistic fiber-tracking with anatomical data, we modelled cholinergic white matter pathways. We assessed pathway integrity across AD continuum stages and DLB, comparing our automated method with the CHolinergic Pathway Hyperintensities Scale (CHIPS) and the Fazekas scale for detecting cerebrovascular disruptions. Additionally, we performed imaging-pathologic validation using post-mortem MRI of autopsy-confirmed AD (n=35), DLB (n=8) and AD+DLB (n=14) cases. Results We observed a progressive decline in cholinergic white matter integrity throughout the AD continuum, starting from SCD to MCI and AD dementia, with early changes in posterior regions extending to anterior frontal white matter. In DLB patients, our automated method strongly correlated with CHIPS, both effectively distinguishing DLB from controls. Post-mortem studies indicated greater degeneration in AD compared to DLB. Conclusions Our findings suggest that alterations in cholinergic white matter pathways manifest as early as SCD and differ between AD and DLB. The integrity of cholinergic pathways may serve as a biomarker for early neurodegeneration in the AD continuum and demonstrates differential sensitivity to AD and DLB pathology.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

20601 - Medical engineering

Project

<a href="/en/project/GM25-18359M" target="_blank" >GM25-18359M: Quantitative Structural and Functional Imaging of the Human Cholinergic System with Applications in Cognitive Science and Neurodegenerative Disorders</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů