Objective: To explore neurophysiological changes using quantitative EEG (qEEG) and transcranial magnetic stimulation (TMS) in PD patients carriers and non-carriers of GBA1 mutations.

Background: qEEG and TMS provide non-invasive measures of cortical neurophysiology and sensorimotor integration. GBA-PD patients often exhibit earlier and more severe motor and cognitive impairment than idiopathic PD (iPD). Comparing these groups may improve understanding of the neural mechanisms underlying greater cognitive involvement and faster disease progression in GBA-PD.

Method: Early PD patients underwent multimodal neurophysiological assessment. Resting-state 64-channel qEEG assessed cortical oscillatory activity, including relative power in delta, theta, alpha, and beta bands. TMS paired with median nerve stimulation assessed sensorimotor integration through short-latency (SAI) and long-latency afferent inhibition (LAI), reflecting cholinergic and cortico-cortical network function. Neurophysiological measures were compared between groups and examined in relation to clinical markers of disease severity and cognition.

Results: Compared to 55 older adults (age 61.9±6.1; MDS-UPDRS III 1.5±1.7), 54 PD patients were included, comprising 30 with iPD (age 58.1±7.5, MDS-UPDRS III 13.9±9.1, LEDD 324±205) and 24 with GBA-PD (age 60.0±9.2, MDS-UPDRS III 17.9±7.5, LEDD 469±267). PD patients showed increased delta power (p<0.036), decreased alpha power (p<0.040), indicating cortical slowing, and reduced short-latency afferent inhibition (p<0.001), reflecting diminished cholinergic activity. MOCA did not differ between groups, while both PD groups had slower gait speed than older adults (p<0.001). Compared with iPD, GBA-PD showed greater SAI reduction and relatively preserved beta activity. Lower SAI correlated with higher MDS-UPDRS III scores (r>0.314, p<0.003). Additionally, beta and delta power correlated with SAI (r>0.358, p<0.01), linking cortical oscillatory changes with cholinergic dysfunction.

Conclusion: PD patients show cortical slowing and reduced cholinergic activity compared with older adults. These alterations are more pronounced in GBA-PD and are linked to changes in cortical oscillatory activity and sensorimotor integration. Together, the findings provide insight into the neural mechanisms underlying greater disease burden and faster progression in GBA-PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-cholinergic-activity-and-electrophysiological-slowing-in-patients-with-gba-pd/