Bridging Bench to Bedside for Brain Health: Non-Invasive Brain Stimulation for Neurodegenerative Diseases

The prevalence and the burden of neurodegenerative diseases is projected to increase in the future, but therapeutic options remain limited, relatively invasive, and not readily accessible. In this context, non-invasive brain stimulation (NIBS) techniques, mainly transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are emerging as safe and reliable instruments to enhance cognitive performance in asymptomatic individuals and patients with cognitive decline. Nevertheless, these techniques face some limitations that delay their deployment in clinical practice. Here, we describe the current status in the development of these technologies for the treatment of neurodegenerative diseases, and we present a novel promising approach for focally and non-invasively target deep brain regions. In light of these technological advances, we then propose a stepwise research roadmap to achieve an effective clinical translation of these techniques. Firstly, the constitution of open-access multimodal databases will allow to inform future interventions and design a new generation of clinical trials. Secondly, research efforts targeting symptomatic patients will need to assess the impact of NIBS techniques in different forms of dementias and probe their efficacy as disease-modifying therapies. In a future step, randomized clinical trials could focus on highly characterized at-risk populations to probe the impact of NIBS in secondary prevention. Once validated on research grounds, these techniques could enter clinical practice, enhancing cognitive performance in asymptomatic individuals and slowing disease progression in symptomatic patients, ultimately lowering the burden of neurodegenerative diseases. Eventually, NIBS techniques could be integrated into clinical practice within the framework of national Brain Health programs to provide early non-invasive interventions against cognitive decline to patients and individuals at risk.