TMS–EEG Co-Registration in Patients with Mild Cognitive Impairment, Alzheimer’s Disease and Other Dementias: A Systematic Review

An established method to assess effective brain connectivity is the combined use of transcranial magnetic stimulation with simultaneous electroencephalography (TMS–EEG) because TMS-induced cortical responses propagate to distant anatomically connected brain areas. Alzheimer’s disease (AD) and other dementias are associated with changes in brain networks and connectivity, but the underlying pathophysiology of these processes is poorly defined. We performed here a systematic review of the studies employing TMS–EEG co-registration in patients with dementias. TMS–EEG studies targeting the motor cortex have revealed a significantly reduced TMS-evoked P30 in AD patients in the temporo-parietal cortex ipsilateral to stimulation side as well as in the contralateral fronto-central area, and we have demonstrated a deep rearrangement of the sensorimotor system even in mild AD patients. TMS–EEG studies targeting other cortical areas showed alterations of effective dorsolateral prefrontal cortex connectivity as well as an inverse correlation between prefrontal-to-parietal connectivity and cognitive impairment. Moreover, TMS–EEG analysis showed a selective increase in precuneus neural activity. TMS–EEG co-registrations can also been used to investigate whether different drugs may affect cognitive functions in patients with dementias.