Identification of early neurophysiological markers related to cognitive-behavioural disorders and progression of Vascular Cognitive Impairment: a Transcranial Magnetic Stimulation study

Abstract

Transcranial magnetic stimulation (TMS) highlighted functional changes in dementia, whereas there are few data in patients with Vascular Cognitive Impairment No Dementia (VCI-ND) at risk for cognitive worsening. Similarly, little is known about the neurophysiological impact of Vascular Depression (VD) on deterioration of cognitive functions. We performed a longitudinal TMS study to test whether the presence of depression might affect not only cognition but also the functioning of specific cortical circuits in patients with subcortical vascular damage. In this study, 16 VCI-ND and 11 VD patients, age-matched with 15 healthy controls, underwent a baseline evaluation including clinical-cognitive, neuroimaging and TMS assessment. After approximately two years of follow-up, all participants were prospectively re-evaluated. At baseline, a significant more pronounced intracortical facilitation (ICF) at paired-pulse TMS was found in VCI-ND patients only. Re-evaluation revealed an increase of the global excitability at single-pulse TMS in both VCI-ND and VD. At follow-up, the ICF of VCI-ND become similar to the other groups. Only VD patients showed cognitive deterioration. In conclusion, in VCI-ND specific measures of cortical excitability, namely the high level of ICF found at baseline, suggests an enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning; conversely, a lack of this hyperfacilitation in VD might be associated with clinical progression. The hyperexcitability to single-pulse TMS observed at follow-up in both group of patients also suggests functional changes in glutamatergic neurotransmission. This suggests that the mechanisms enhancing the risk of dementia in VD might be related either to subcortical changes produced by vascular lesions or to the lack of compensatory functional cortical changes.