Objective: To investigate compensatory dynamic brain network mechanisms in early Lewy body dementia (LBD), specifically mild cognitive impairment with Lewy bodies (MCI-LB), using resting-state functional MRI (rs-fMRI) and fast eigenvector centrality (FEC), and to examine their relationship with cognition.

Background: Lewy body dementia (LBD) is the second most common degenerative dementia, with MCI-LB representing its early stage [1, 2]. While with rs-fMRI is possible to detect brain network changes in LBD [3], understanding the dynamic compensatory mechanisms in the early stages is crucial. We hypothesized that alterations in the dynamic functional connectivity (dFC) of networks involved in LBD progression – including the sensorimotor (SMN), dorsal attention (DAN), visual (VN), default mode (DMN), and frontoparietal control (FPCN) networks – reflect compensatory processes.

Method: Rs-fMRI data were acquired from 30 medication-naïve MCI-LB patients and 55 healthy controls (HC). FEC was used to identify dFC states through a sliding window approach. Correlation analyses were performed between state density/dwell time and cognitive domain z-scores for attention, executive, and visuospatial functions.

Results: Four distinct dFC states were identified, encompassing hubs of the SMN, DAN, VN, DMN, and FPCN. In MCI-LB, but not in HC, a state involving the hubs of the SMN, DAN, and VN showed significant correlations: increased density (R = 0.538, p = 0.005) and decreased mean dwell time (R = -0.606, p = 0.002) were associated with better visuospatial function, suggesting enhanced network flexibility as a compensatory mechanism. In another state involving the FPCN and SMN, dwell time was positively correlated with visuospatial function (R = 0.542, p = 0.004), indicating increased network stability as another form of compensation.

Conclusion: MCI-LB patients engage distinct brain networks associated with visuospatial processing control. The positive correlations with cognitive z-scores suggest a compensatory mechanism that may enhance visuospatial function in the early stages of LBD. Through dFC analysis, we identified two key mechanisms linked to visuospatial variability in MCI-LB: the flexibility of networks involved in visuospatial processing and the stability of the network responsible for switching between task-positive and task-negative brain networks.

References: [1] Goodman RA, Lochner KA, Thambisetty M, Wingo TS, Posner SF, Ling SM. Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011–2013. Alzheimer’s & Dementia. 2017;13(1):28-37. doi:10.1016/j.jalz.2016.04.002.

[2] McKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020;94(17):743-55. doi:10.1212/WNL.0000000000009323.

[3] Schumacher J, Peraza LR, Firbank M, Thomas AJ, Kaiser M, Gallagher P, O’Brien JT, Blamire AM, Taylor JP. Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer’s disease. Neuroimage Clin. 2019;22:101812. doi:10.1016/j.nicl.2019.101812.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/compensatory-dynamic-brain-network-mechanisms-in-early-lewy-body-dementia-an-rs-fmri-study/