Transcranial Magnetic Stimulation in Dementia: From Pathophysiology to Treatment

Abstract

Alzheimer’s disease (AD) is one of the most devastating forms of dementia. At present, there are no treatments of value and therefore patients with AD have an uncertain future, due to the current incapability to envisage the course of the disease. This is mainly due to the lack of understanding of the underlying pathophysiology and to the huge patients’ clinical heterogeneity. In this regard, recent evidence reinforced the notion that synaptic dysfunction could be a relevant aspect of AD-related pathophysiology. In particular, it has been shown that loss of synaptic density occurs since the early phases of the disease, and that synaptic failure is an early event that precedes neuronal degeneration. Such remarkable weakening of synaptic transmission is supposed to play a key role in the pathogenesis of different forms of dementia, including AD, frontotemporal dementia, and Lewy body dementia. However, despite this emerging background, it has not been possible to quantify synaptic functioning (or dysfunction) directly in vivo in AD patients. Transcranial magnetic stimulation (TMS) has been recently introduced as a novel approach able to identify the early signatures of synaptic dysfunction characterizing the different forms of AD. In the current chapter, I review the novel emerging neurophysiological signatures of AD that have been highlighted in vivo by TMS studies. I show how TMS measurement of neurophysiological activity may provide novel biomarkers useful to increase the accuracy of differential diagnosis, to predict disease progression, and to anticipate response to therapy. Recently, different forms of noninvasive brain stimulation techniques (e.g., repetitive TMS, rTMS) have been applied to patients with AD in order to improve cognitive decline and behavioral disorders. In recent years, treatments based on multiple sessions of rTMS have represented a promising tool for influencing cognition in people with neurodegenerative diseases. In the second part of this chapter, I also consider novel therapeutic approaches based on the clinical use of rTMS.