Neuromodulation in the Treatment of Alzheimer’s Disease: Current and Emerging Approaches

Article type: Review Article

Authors: Pople, Christopher B.^a | Meng, Ying^{a; b} | Li, Daniel Z.^a | Bigioni, Luca^a | Davidson, Benjamin^{a; b} | Vecchio, Laura M.^c | Hamani, Clement^{a; b} | Rabin, Jennifer S.^{a; d; e} | Lipsman, Nir^{a; b; *}

Affiliations: [a] Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, ON, Canada | [b] Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada | [c] Biological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada | [d] Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada | [e] Rehabilitation Sciences Institute, University of Toronto, Toronto ON, Canada

Correspondence: [*] Correspondence to: Nir Lipsman, MD, PhD, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Tel.: +1 416 480 6954; E-mail: nir.lipsman@sunnybrook.ca.

Abstract: Neuromodulation as a treatment strategy for psychiatric and neurological diseases has grown in popularity in recent years, with the approval of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression being one such example. These approaches offer new hope in the treatment of diseases that have proven largely intractable to traditional pharmacological approaches. For this reason, neuromodulation is increasingly being explored for the treatment of Alzheimer’s disease. However, such approaches have variable, and, in many cases, very limited evidence for safety and efficacy, with most human evidence obtained in small clinical trials. Here we review work in animal models and humans with Alzheimer’s disease exploring emerging neuromodulation modalities. Approaches reviewed include deep brain stimulation, transcranial magnetic stimulation, transcranial electrical stimulation, ultrasound stimulation, photobiomodulation, and visual or auditory stimulation. In doing so, we clarify the current evidence for these approaches in treating Alzheimer’s disease and identify specific areas where additional work is needed to facilitate their clinical translation.

Keywords: Alzheimer’s disease, deep brain stimulation, neuromodulation, photobiomodulation therapy, pulsed ultrasound, transcranial electrical stimulation, transcranial magnetic stimulation

DOI: 10.3233/JAD-200913

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1299-1313, 2020