Transcranial magnetic stimulation intervention in Alzheimer’s disease: a research proposal for a randomized controlled trial

Abstract

ObjectiveAlzheimer’s disease is a major health problem in our society. To date, pharmacological treatments have obtained poor results and there is a growing interest in finding non-pharmacological interventions for this disease. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able to induce changes in brain activity and long-term modifications in impaired neural networks, becoming a promising clinical intervention. Our goal is to study the benefit of individualized TMS targeting based on the patient’s functional connectivity (personalized targeting), and short duration TMS protocol, instead of current non-individualized and longer session approaches. A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, 1 month, 3 months and 6 months after the end of the intervention. Fifty-four patients with a diagnosis of Alzheimer’s disease will be randomly allocated into experimental (active TMS), sham control, or conventional intervention control group. We will quantify changes in cognitive, functional, and emotional deficits in Alzheimer patients, as well as the functional connectivity changes induced by the TMS treatment.ResultsWe expect to demonstrate that personalized TMS intervention has a measurable positive impact in cognition, emotion, daily living activities and brain connectivity, thus representing a potential treatment for Alzheimer’s disease.Trial registration The trial has been prospectively registered at ClinicalTrials.gov, identifier NCT03121066. Date of registration: 04/19/2017

Transcranial Magnetic Stimulation in Alzheimer’s Disease: Are We Ready?

“…Other mechanisms implicated in the pathogenesis of AD that might contribute to the cognitive effects of rTMS in AD include neurochemical modulation (Michael et al, 2003;Strafella et al, 2003), epigenetic modification of gene transcription (Etiévant et al, 2015), and modulatory effects on neural network dynamics in vulnerable circuitry (Marron et al, 2018). The effect of TMS on these and other potential mechanisms, however, has received limited attention.…”

“…The effects of high-frequency stimulation have been tested most often, with positive studies reporting a variable degree of cognitive benefit, at least in mild AD. Insufficient attention has been directed at tracking the influence of TMS on AD pathogenesis or biomarkers (i.e., proxies of the underlying disease process; for example, see Marron et al, 2018). Nonetheless, substantial evidence indicates that neuronal activity promotes amyloid deposition, raising the possibility that the same highfrequency stimulation that leads to improved clinical symptoms might also accelerate underlying AD pathogenesis.…”

Effect of alcohol on the central nervous system to develop neurological disorder: pathophysiological and lifestyle modulation can be potential therapeutic options for alcohol-induced neurotoxication

“…TMS along with fMRI can be used to study neuronal connectivity and excitability, recently this treatment option was used to reduce dementia and induce remission for individuals with the major depressive disorder [138] , [139] . Sometimes it is also experimentally used as a stimulant for myelination and to restore neuronal function in neurodegenerative diseases like multiple sclerosis and Alzheimer's disease [22] , [140] . It is believed by several researchers that each glial cell has the ability to respond to the currents induced by TMS and play a role in enhancing the proliferation of adult progenitor and neuronal stem cells but there is less evidence on cell survival and cell differentiation process [66] , [108] .…”

Virtual reality-based cognitive healthcare interventions: User-centered design considerations, guidelines and framework

“…Another possibility is the development of novel mixed modality interventions by integrating into the VR platform any of several existing or emerging minimally invasive neurotechnological procedures, e.g. Transcranial Magnetic Stimulations (tMS) (Nguyen et al, 2017;Marron et al, 2018). • Ecological validity: The excellent ability to represent real life in highly immersive scenarios allows 3D VR ▪ Relative scientific weakness of presently existing evidence could affect adoption ▪ Non-existing or conflicting healthcare regulations and policies ▪ Interfering commercial business interests technologies to be capable of providing highly realistic customizable dynamic environments.…”