Cortical excitability changes as a marker of cognitive impairment in Parkinson's disease

Cognitive impairment of different severity with eventual progression to dementia in Parkinson's disease (PD) appears during the course of the disease. In this study, transcranial magnetic stimulation (TMS) was used to assess cortical excitability changes in PD patients with varying cognitive impairment. We aimed to identify the TMS parameters that could serve as a non-invasive marker of cognitive impairment in patients with PD. Consecutive PD patients were recruited in the study. Detailed neuropsychological assessment was carried out to identify PD without cognitive impairment (PD-nC), PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD). Twenty patients of PDD (2 females and 18 males), 20 PD-MCI (4 females and 16 males), 18 PD-nC (5 females, 13 males) and 18 healthy controls (4 females, and 14 males) were included in the study. All the participants underwent TMS with recording of resting motor threshold, central motor conduction time, silent period, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). All the groups were age matched. The SICI was present in all; however, significantly greater inhibition was noted in PDD (Mean +/- SD; 0.11 +/- 0.08) followed by PD-MCI (0.31 +/- 0.17), PD-nC (0.49 +/- 0.26) and controls (0.61 +/- 0.23; p < 0.001). The ICF was significantly reduced in PDD (Mean +/- SD; 0.15 +/- 0.18), PD-MCI (0.55 +/- 0.31), PD-nC (0.96 +/- 0.59), when compared to healthy controls (1.81 +/- 0.83; p < 0.001). Patients with PD-nC, PD-MCI and PDD had graded reduction in ICF and increasing intracortical inhibition as the disease progressed from PD-nC through PD-MCI to PDD. This suggests progressive overactivity of GABAergic transmission, glutaminergic deficiency with consequent reduction of cholinergic transmission leading to dementia.