Objective: To explore the differences in the structure of event-related oscillations (ERO) elicited by a visual oddball task in Dementia with Lewy bodies (DLB) patients with and without mutations in the GBA gene.

Background: ERO elicited during an oddball task have been traditionally used to explore neurophysiological underpinning of cognitive function. Delta band oscillatory responses have been indicated specifically in decision-making and attentional processes and have been reported as a general EEG marker of cognitive dysfunction. Mutations in the GBA gene have been indicated as contributors to neurodegenerative diseases such as Parkinson’s disease or DLB with a specific contribution to cognitive dysfunction.

Method: EEG was recorded from the Fz, Cz and Pz electrodes during a visual oddball task in 19 clinically diagnosed Ashkenazi Jewish patients with DLB who underwent genotyping for mutations in the GBA gene. Time-frequency power and inter-trial phase clustering were calculated from the results of Morlet wavelet convolution.

Results: Eight patients were carriers of the N370S mutation in the GBA gene and 11 were non-carriers. Carriers were younger in age (67.0±4.5yrs vs. 75.1±5.2, p=0.004), but had similar percent males (88% vs. 91%), disease duration (4.4±3.1yrs vs. 3.6±1.8yrs), cognitive function (MoCA score: 17.8±6.2 vs. 21.0±5.0) and motor symptoms (MDS-UPDRS-III: 33.4±17.5 vs. 36.2±16.0).  Task performance was comparable between groups, including similar reaction time and reaction time variability. Within-group EEG analysis revealed that in non-carriers, both event-related power and phase coherence were increased in the delta band as compared to the baseline period (p<0.009, Cohen’s d>1.0). In GBA mutation carriers only event-related phase coherence, but not power significantly increased compared to the baseline period. Between-group analysis revealed that event-related power was decreased in carriers compared to non-carriers in delta band at Fz and Cz (p<0.04, Cohen’s d<-0.9).

Conclusion: Our findings show reduced event-related power in DLB patients with the N370S  mutation in the GBA gene compared to non-carriers, potentially signifying more pronounced network dysfunction. Interestingly, behavioral performance was comparable, and event-related coherence was intact in both groups, suggesting a possible compensatory effect that may involve other brain regions. This should be further explored.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/event-related-oscillations-in-patients-with-dementia-with-lewy-bodies-with-and-without-mutations-in-the-gba-gene/