Neurophysiological Correlates of Motor and Cognitive Dysfunction in Prodromal and Overt Dementia with Lewy Bodies

Background: The neurophysiological correlates of cognitive and motor symptoms in prodromal and overt dementia with Lewy bodies (DLB) are still to be elucidated. Objective: To evaluate if cognitive and motor features of patients with prodromal and overt DLB are associated with the impairment of specific neurotransmitter circuits, evaluated in vivo with transcranial magnetic stimulation (TMS). Methods: Fifty-one patients with DLB (twenty-five prodromal; twenty-six with dementia) underwent neuropsychological and clinical evaluation, with twenty-five patients having at least one follow-up evaluation. All patients were assessed with TMS at baseline, with protocols assessing cholinergic circuits (short latency afferent inhibition, SAI), GABAergic circuits (short interval intracortical inhibition, SICI), and glutamatergic circuits (intracortical facilitation, ICF). Results: Compared to HC, SICI, ICF, and SAI resulted significantly impaired in both prodromal and overt DLB, with the latter showing a reduced SICI and SAI also compared to prodromal DLB. There was a significant correlation between motor deficits, evaluated with the UPDRS-III, and the impairment of GABAergic (SICI) (r= 0.729, p < 0.001) and glutamatergic (ICF) (r=0.608, p < 0.001) circuits; global cognition, evaluated with the Mini-Mental State Examination, correlated with the impairment of cholinergic (SAI) circuits (r=-0.738, p < 0.001). Worsening of cognitive functions at follow-up was associated with reduced cholinergic functions at baseline (R-2 = 0.53, p < 0.001). Conclusion: These results suggest that motor and cognitive dysfunctions in prodromal and overt DLB depend on specific and independent neurotransmitter circuits.