Network Signatures of Disease Progression and Core Symptoms in Dementia with Lewy Bodies Distinct from Alzheimer's Disease

Gabriel, V.; Chabran, E.; Sourty, M.; Cretin, B.; Philippi, N.; Muller, C.; Anthony, P.; Demuynck, C.; Loureiro de Sousa, P.; Botzung, A.; Sanna, L.; Bousiges, O.; Blanc, F.

doi:10.1101/2025.07.17.665279

bioRxiv · 10.1101/2025.07.17.665279

Network Signatures of Disease Progression and Core Symptoms in Dementia with Lewy Bodies Distinct from Alzheimer's Disease

Gabriel, V.·Chabran, E.·Sourty, M.·Cretin, B.·Philippi, N.·Muller, C.·Anthony, P.·Demuynck, C.·Loureiro de Sousa, P.·Botzung, A.·Sanna, L.·Bousiges, O.·Blanc, F.

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Abstract

BackgroundResting-state fMRI studies in dementia with Lewy bodies (DLB) and Alzheimers disease (AD) have described connectivity alterations in large-scale brain networks. However, little is known about functional changes across disease stages, particularly in DLB. ObjectiveTo investigate functional connectivity of key brain networks in DLB patients at different stages, compare them to AD and healthy controls (HC) and examine associations with core clinical symptoms. MethodsNinety DLB patients, comprising 63 with mild cognitive impairment (MCI-DLB) and 27 with dementia (d-DLB), along with 25 AD patients (11 MCI-AD and 14 d-AD) and 34 HC underwent clinical, neuropsychological and resting-state fMRI assessment. ROI-to-ROI analyses were performed using the CONN toolbox, (pFDR<0.05). ResultsThe DLB group showed reduced functional connectivity within the salience network (SN) compared with HC, but did not differ from AD. While MCI-DLB patients showed no significant differences, d-DLB patients showed reduced SN and frontoparietal network (FPN) connectivity compared to HC and AD. SN connectivity was associated with severity of fluctuations and FPN connectivity with REM sleep behavior disorder and cognitive decline in DLB. In contrast, in the AD group, decreased default mode network (DMN) connectivity was associated with lower MMSE scores. ConclusionSN and FPN connectivity impairments relate to disease progression and core clinical features in DLB, whereas DMN connectivity is linked to cognitive decline in AD. These distinct patterns highlight divergent paths of network dysfunction in the two diseases, offering insight into their underlying mechanisms and clinical expression.

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Gabriel, V., Chabran, E., Sourty, M., Cretin, B., Philippi, N., Muller, C., Anthony, P., Demuynck, C., Loureiro de Sousa, P., Botzung, A., Sanna, L., Bousiges, O., Blanc, F.. 2025-07-21. Network Signatures of Disease Progression and Core Symptoms in Dementia with Lewy Bodies Distinct from Alzheimer's Disease. https://doi.org/10.1101/2025.07.17.665279

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