Neurostimulation Combined With Cognitive Intervention in Alzheimer’s Disease (NeuroAD): Study Protocol of Double-Blind, Randomized, Factorial Clinical Trial

Andrade, Suellen Marinho; Oliveira, Eliane Araújo de; Torro-Alves, Nelson; Santos, Ana Cristina Gomes; Mendonça, Camila Teresa Ponce Leon de; Sampaio, Danielle Dorand Amorim; Silva, Edyllaine Elidy Querino Cavalcante da; Fonsêca, Égina Karoline Gonçalves da; Rodrigues, Evelyn Thais de Almeida; Lima, Gabriela Nayara Siqueira de; Carvalho, Jamerson; Silva, Jessyca Alves Silvestre da; Toledo, Manuella; Rosa, Marine Raquel Diniz da; Gomes, Marcia Queiroz de Carvalho; Oliveira, Melquisedek Monteiro de; Lemos, Moema Teixeira Maia; Lima, Nágylla Gomes; Inácio, Penha; Rodrigues, Petra Maria da Cruz Ribeiro e; Ferreira, Rayssa Gabriela Dantas; Cavalcante, Renata; Aranha, Renata Emanuela Lyra de Brito; Neves, Regina Dias; Souza, Rodrigo Marmo da Costa e; Portugal, Thainá Magalhães; Martins, Wanessa Kallyne Nascimento; Pontes, Vívian Volkmer; Fernandes, Thiago Monteiro de Paiva; Contador, Israel; Fernández‐Calvo, Bernardino

doi:10.3389/fnagi.2018.00334

Cited by 10 publications

(6 citation statements)

References 104 publications

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“…At each site, cognitive training was provided together with rTMS. 50 However, despite some positive effects, an FDA advisory panel voted against recommending this system for the treatment of AD in 2019.…”

Section: Neurodegenerative Diseasementioning

confidence: 99%

Transcranial Magnetic Stimulation for the Neurological Patient: Scientific Principles and Applications

2022

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Non-invasive brain stimulation has been increasingly recognized for its potential as an investigational, diagnostic and therapeutic tool across the clinical neurosciences. Transcranial magnetic stimulation (TMS) is a non-invasive method of focal neuromodulation. Diagnostically, TMS can be used to probe cortical excitability and plasticity, as well as for functional mapping. Therapeutically, depending on the pattern employed, TMS can either facilitate or inhibit stimulated cortex potentially modulating maladaptive physiology through its effects on neuroplasticity. Despite this potential, applications of TMS in neurology have only been approved for diagnostic clinical neurophysiology, pre-surgical mapping of motor and language cortex, and the treatment of migraines. In this article, we discuss the principles of TMS and its clinical applications in neurology, including experimental applications in stroke rehabilitation, seizures, autism spectrum disorder, neurodegenerative disorders, movement disorders, tinnitus, chronic pain and functional neurological disorder. To promote increased cross-talk across neurology and psychiatry, we also succinctly review the TMS literature for the treatment of major depression and obsessive compulsive disorder. Overall, we argue that larger clinical trials that are better informed by circuit-level biomarkers and pathophysiological models will lead to an expansion of the application of TMS for patients cared for by neurologists.

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Section: Neurodegenerative Diseasementioning

confidence: 99%

Transcranial Magnetic Stimulation for the Neurological Patient: Scientific Principles and Applications

2022

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“…The "neuroAD protocol" is another line of research using a multitarget rTMS approach [67,68,102,103]. The protocol involves stimulation of six distinct targets regions: left and right dlPFC, left and right somatosensory association cortex, Broca's area, and Wernicke's area.…”

Section: Multitarget Stimulationmentioning

confidence: 99%

“…During each stimulation session, three of the six targets were stimulated in series. Three different brain regions were selected for stimulation every session, with each site being stimulated in 15 sessions [102]. Studies stimulating at 100-110% RMT reported significant improvement in ADAS-Cog performance following rTMS [69].…”

Section: Multitarget Stimulationmentioning

confidence: 99%

Stimulating Memory: Reviewing Interventions Using Repetitive Transcranial Magnetic Stimulation to Enhance or Restore Memory Abilities

2021

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Human memory systems are imperfect recording devices that are affected by age and disease, but recent findings suggest that the performance of these systems may be modifiable through interventions using non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). The translational potential of these rTMS interventions is clear: memory problems are the most common cognitive complaint associated with healthy aging, while pathological conditions such as Alzheimer’s disease are often associated with severe deficits in memory. Therapies to improve memory or treat memory loss could enhance independence while reducing costs for public health systems. Despite this promise, several important factors limit the generalizability and translational potential of rTMS interventions for memory. Heterogeneity of protocol design, rTMS parameters, and outcome measures present significant challenges to interpretation and reproducibility. However, recent advances in cognitive neuroscience, including rTMS approaches in addition to a new understanding of functional brain networks and related insights, may offer methodological tools necessary to design new interventional studies with enhanced experimental rigor, improved reproducibility, and greater likelihood of successful translation to clinical settings. In this review, we first discuss the current state of the literature on memory modulation with rTMS, then offer a commentary on developments in cognitive neuroscience that are relevant to rTMS interventions, and finally close by offering several recommendations for the design of future investigations using rTMS to modulate human memory performance.

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“…Human studies applying GammaSense stimulation in MCI or AD are currently ongoing, though a small pilot study in 10 patients on 40 Hz light therapy had no effects on Aβ load [304], (Table 4). Some groups have also coupled TMS or tDCS with cognitive stimulation [305,306], (Table 4). Other devices, such as NeuroEM, based on Transcranial Electromagnetic Treatment (TEMT), seem to show promising results [307], and clinical trials to assess its efficacy are currently ongoing (Table 4).…”

Section: Therapeutic Toolsmentioning

confidence: 99%

Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’s Disease

Toniolo

Sen

2020

IJMS

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People with Alzheimer’s disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxic proteins, and ultimately to further neurodegeneration and neuronal silencing mediated by concomitant tau accumulation. Several neurotransmitters participate in the initial hyperexcitable state, with increased synaptic glutamatergic tone and decreased GABAergic inhibition. These changes appear to activate excitotoxic pathways and, ultimately, cause reduced long-term potentiation, increased long-term depression, and increased GABAergic inhibitory remodelling at the network level. Brain hyperexcitability has therefore been identified as a potential target for therapeutic interventions aimed at enhancing cognition, and, possibly, disease modification in the longer term. Clinical trials are ongoing to evaluate the potential efficacy in targeting hyperexcitability in AD, with levetiracetam showing some encouraging effects. Newer compounds and techniques, such as gene editing via viral vectors or brain stimulation, also show promise. Diagnostic challenges include identifying best biomarkers for measuring sub-clinical epileptiform discharges. Determining the timing of any intervention is critical and future trials will need to carefully stratify participants with respect to the phase of disease pathology.

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Neurostimulation Combined With Cognitive Intervention in Alzheimer’s Disease (NeuroAD): Study Protocol of Double-Blind, Randomized, Factorial Clinical Trial

Cited by 10 publications

References 104 publications

Transcranial Magnetic Stimulation for the Neurological Patient: Scientific Principles and Applications

Transcranial Magnetic Stimulation for the Neurological Patient: Scientific Principles and Applications

Stimulating Memory: Reviewing Interventions Using Repetitive Transcranial Magnetic Stimulation to Enhance or Restore Memory Abilities

Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’s Disease

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