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Medicina
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Efficacy of Transcranial Electrical Current and Magnetic Stimulation Treatment Options...
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Efficacy of Transcranial Electrical Current and Magnetic Stimulation Treatment Options for Alzheimer’s Disease

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Neurology".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 7744

Special Issue Editor

Dr. Zahra Moussavi

E-Mail Website
Guest Editor
Riverview Health Center, University of Manitoba, Winnipeg, MB, Canada
Interests: Alzheimer’s diagnosis and its treatment by non-pharmaceutical means; biological signal analysis; obstructive sleep apnea diagnosis; instrumentation for medical devices

Special Issue Information

Dear Colleagues,

Neurodegenerative dementia, in particular Alzheimer’s disease (AD), is a global crisis with no existing cure. Technologies targeting the neuroplasticity of the brain offer hope for slowing its progression, avoiding further decline, and even reversing the decline. The use of non-pharmaceutical treatments, mainly either transcranial electrical or magnetic stimulation, to induce brain neuroplasticity has been on the rise significantly in the last decade. Alzheimer’s disease is characterized by progressive decline in cognitive functions that is associated with neuronal loss as well as characteristic markers such as b-amyloid plaques and neurofibrillary tangles. In order to counteract the effects of neuronal death, and the particular susceptibility of cholinergic cells in AD, most pharmacological treatments rely on acetylcholinesterase inhibitors to increase the excitability of cells that respond to acetylcholine. Thus, the target of the current treatments is to increase the excitability and activity of remaining cells in order to counteract the decline in brain function.

There are several parameters to choose when designing a protocol for either transcranial electrical or magnetic stimulation of the brain as a treatment for AD. The purpose of this Special Issue is to discuss the most important contributing parameters, their pros and cons, and their efficacy with the hope that we get closer to achieving optimized non-pharmaceutical treatments for individuals affected by AD.

Dr. Zahra Moussavi
Guest Editor

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Keywords

  • transcranial electrical current estimation
  • transcranial magnetic stimulation
  • Alzheimer’s disease
  • deep current stimulation

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Published Papers (3 papers)

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Research

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21 pages, 1313 KB  
Article
Cognitive and Neuropsychiatric Effects of 40 Hz tACS Simultaneously with Cognitive Exercises for Dementia: A Randomized, Crossover, Double-Blind, Sham-Controlled Study
by Maria Anabel Uehara, Sumeet Kalia, Mari Garcia Campuzano, Mohammad Jafari-Jozani, Brian Lithgow and Zahra Moussavi
Medicina 2025, 61(4), 757; https://doi.org/10.3390/medicina61040757 - 19 Apr 2025
Cited by 1 | Viewed by 2119
Abstract
Background and Objectives: Transcranial alternating current stimulation (tACS) at 40 Hz has shown potential to enhance cognitive function. However, research on its combination with cognitive exercises, particularly its long-term effects in a dementia population, remains limited. This study investigated the effects of [...] Read more.
Background and Objectives: Transcranial alternating current stimulation (tACS) at 40 Hz has shown potential to enhance cognitive function. However, research on its combination with cognitive exercises, particularly its long-term effects in a dementia population, remains limited. This study investigated the effects of 40 Hz tACS paired with simultaneous cognitive exercises on cognition, neuropsychiatric symptoms, and the depression status of individuals with dementia in a sham-controlled, double-blind crossover design. Materials and Methods: A total of 42 participants with dementia were randomized into two groups: (1) the R1S2 group received 40 Hz real tACS with cognitive exercises, followed by a ≥8-week washout period, and then sham tACS with cognitive exercises; (2) the S1R2 group received the reversed sequence. tACS was applied at 1.5 mA peak-to-peak with electrodes over the left dorsolateral prefrontal cortex and contralateral supraorbital area. Participants received two 30 min stimulation sessions per day, 5 days per week, for 4 consecutive weeks, paired with cognitive exercises using the MindTriggers app (2.9.1). The primary outcome was the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the secondary outcomes included the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). All outcome measures were assessed before and after each treatment block. Results: Real tACS paired with cognitive exercises significantly improved ADAS-Cog scores post-treatment compared to pre-treatment (p-value = 0.019), whereas sham tACS did not. Furthermore, real tACS produced significant long-term improvements approximately 2–3 months post-treatment in ADAS-Cog scores compared to sham (p-value = 0.048). Both real (p-value = 0.003) and sham (p-value = 0.015) tACS significantly reduced NPI-Q scores post-treatment. MADRS scores significantly improved (p-value = 0.007) post-treatment for real tACS but not sham. Conclusions: The 40 Hz tACS paired with cognitive exercises improves cognition, neuropsychiatric symptoms, and depression post-treatment in dementia, with sustained cognitive effects. The findings highlight its potential as a non-invasive therapeutic intervention for dementia. Full article
(This article belongs to the Special Issue Efficacy of Transcranial Electrical Current and Magnetic Stimulation Treatment Options for Alzheimer’s Disease)
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Review

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41 pages, 1234 KB  
Review
Targeting Neural Oscillations for Cognitive Enhancement in Alzheimer’s Disease
by Federica Palacino, Paolo Manganotti and Alberto Benussi
Medicina 2025, 61(3), 547; https://doi.org/10.3390/medicina61030547 - 20 Mar 2025
Cited by 7 | Viewed by 4066
Abstract
Alzheimer’s disease (AD), the most prevalent form of dementia, is marked by progressive cognitive decline, affecting memory, language, orientation, and behavior. Pathological hallmarks include extracellular amyloid plaques and intracellular tau tangles, which disrupt synaptic function and connectivity. Neural oscillations, the rhythmic synchronization of [...] Read more.
Alzheimer’s disease (AD), the most prevalent form of dementia, is marked by progressive cognitive decline, affecting memory, language, orientation, and behavior. Pathological hallmarks include extracellular amyloid plaques and intracellular tau tangles, which disrupt synaptic function and connectivity. Neural oscillations, the rhythmic synchronization of neuronal activity across frequency bands, are integral to cognitive processes but become dysregulated in AD, contributing to network dysfunction and memory impairments. Targeting these oscillations has emerged as a promising therapeutic strategy. Preclinical studies have demonstrated that specific frequency modulations can restore oscillatory balance, improve synaptic plasticity, and reduce amyloid and tau pathology. In animal models, interventions, such as gamma entrainment using sensory stimulation and transcranial alternating current stimulation (tACS), have shown efficacy in enhancing memory function and modulating neuroinflammatory responses. Clinical trials have reported promising cognitive improvements with repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), particularly when targeting key hubs in memory-related networks, such as the default mode network (DMN) and frontal–parietal network. Moreover, gamma-tACS has been linked to increased cholinergic activity and enhanced network connectivity, which are correlated with improved cognitive outcomes in AD patients. Despite these advancements, challenges remain in optimizing stimulation parameters, individualizing treatment protocols, and understanding long-term effects. Emerging approaches, including transcranial pulse stimulation (TPS) and closed-loop adaptive neuromodulation, hold promise for refining therapeutic strategies. Integrating neuromodulation with pharmacological and lifestyle interventions may maximize cognitive benefits. Continued interdisciplinary efforts are essential to refine these approaches and translate them into clinical practice, advancing the potential for neural oscillation-based therapies in AD. Full article
(This article belongs to the Special Issue Efficacy of Transcranial Electrical Current and Magnetic Stimulation Treatment Options for Alzheimer’s Disease)
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Other

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44 pages, 2613 KB  
Systematic Review
Non-Invasive Brain Stimulation for Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives
by Jacopo Della Toffola, Edoardo Ricci, Magda Quagliotto, Paolo Manganotti and Alberto Benussi
Medicina 2025, 61(9), 1685; https://doi.org/10.3390/medicina61091685 - 17 Sep 2025
Viewed by 965
Abstract
Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, with a bleak prognosis and few treatment options. Non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct [...] Read more.
Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, with a bleak prognosis and few treatment options. Non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), represent emerging approaches aimed at modulating cortical hyperexcitability, a relevant pathogenetic mechanism in ALS. Materials and Methods: A systematic review of the literature was conducted following the PRISMA guidelines, exploring the Scopus and PubMed databases from April to June 2025 with terms related to ALS and NIBS. A total of 18 relevant studies were selected from the initial 708 articles, analysing stimulation protocols, clinical and neurophysiological outcomes, and associated biomarkers; their validity was assessed using the revised Cochrane risk-of-bias (RoB2) tool. Results: The selected studies were extremely heterogeneous, with NIBS techniques, including magnetic (rTMS, cTBS, tSMS) and electrical (tDCS) stimulation, showing variable effects. Low-frequency protocols (1 Hz rTMS) and cTBS showed a slight slowing of clinical progression, while prolonged home stimulation with tDCS and tSMS showed more significant improvements in terms of efficacy, tolerability, and adherence. The main limitations concern the heterogeneity of patients and protocols and the lack of standardised biomarkers, which is why the analysis remained at a descriptive level. The use of telemonitoring and caregiver training are essential to ensure safety and accessibility. Conclusions: NIBS represents a promising therapeutic approach for ALS, but further multicentre, standardised studies with prolonged follow-up are needed. Future strategies should include customisation of stimulation, combination with other therapies, and extension of application to pre-symptomatic phases. Full article
(This article belongs to the Special Issue Efficacy of Transcranial Electrical Current and Magnetic Stimulation Treatment Options for Alzheimer’s Disease)
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