Brain Dynamics as Confirmatory Biomarker of Dementia with Lewy Bodies Versus Alzheimer’s Disease - an Electrophysiological Study

Abstract

Introduction Dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD) and Alzheimer’s disease dementia (AD) are associated with different pathologies. Nevertheless, symptomatic overlap between these conditions may lead to misdiagnosis. Resting-state functional connectivity features in DLB as assessed with electroencephalography (EEG) are emerging as diagnostic biomarkers. However, their pathological significance is still questioned. This study aims to further investigate this aspect and to infer functional and structural sources of EEG abnormalities in DLB. Methods Graph theory analysis was first performed to assess EEG network differences between healthy controls (HC) and dementia groups. Source localisation and Network Based Statistics (NBS) were used to infer EEG cortical network and dominant frequency (DF) alterations in DLB compared with AD. Further analysis aimed to assess the subnetwork associated with visual hallucination (VH) symptom in DLB and PDD, i.e. LBD, compared with not-hallucinating (NVH) patients. Finally, probabilistic tractography was performed on diffusion tensor imaging (DTI) data between cortical regions, thalamus, and basal forebrain (NBM). Correlation between structural and functional connectivity was tested. Results EEG α-band (7-13.5 Hz) network features were affected in LBD compared with HC, whilst DLB β-band network (14-20.5 Hz) was weaker and more segregated when compared with AD. This scenario replicated in the source domain. DF was significantly lower in DLB compared with AD, and positively correlated with structural connectivity strength between NBM and the cortex. Functional visual ventral network connectivity and cholinergic projections towards the cortex were affected in VH compared with NVH, and significantly correlated in NVH. Conclusions Functional connectivity as assessed with EEG is more affected in DLB compared with AD. Moreover, the visual ventral network is functionally altered in VH compared with NVH. Results from structural analysis provide empirical evidence on the role of cholinergic dysfunctions in DLB and PDD pathology and corresponding functional correlates.