Assessment of Effectiveness and Safety of Transcranial Magnetic Stimulation (rTMS) Combined With Transcranial Direct Current Stimulation (tDCS) in Dementia Treatment in Alzheimer's Disease

Study Overview
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Brief Summary
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Alzheimer's disease is the most common disease responsible for dementia, accounting for 40-70% of all dementia cases. Alzheimer's disease is characterized by a gradual and slow decline in memory and other cognitive functions and activities. The medications currently used in Alzheimer's disease were introduced in the 1990s and exhibit insufficient effectiveness. Despite their use, the disease rapidly progresses, leading to complete loss of independence and death. There are conducted numerous studies on new molecules, however none of them has been successfully accomplished so far. Transcranial magnetic stimulation (TMS) is one of the youngest electrophysiological methods, enabling non-invasive and painless stimulation of the central and peripheral nervous system. Another non-invasible neurophysiological method that is utilized in treating patients with neurological dysfunctions and mental disorders is Transcranial direct current stimulation (tDCS). Clinical trials conducted with isolated usage of rTMS and tDCS showed a positive effect of these methods on the enhancement of cognitive functions in patients with Alzheimer's disease. The aim of the project is to evaluate the effectiveness and safety of the combination of Repetitive Transcranial Magnetic Resonance (rTMS) with Transcranial direct current stimulation in the treatment of Alzheimer's dementia. The primary goal of the project is to assess whether the use of combined tDCS and rTMS therapies in patients diagnosed with mild to moderate Alzheimer's disease improves patients' cognitive functions, including memory, attention, thinking, executive and language functions. The research hypothesis assumes that the combination of rTMS and tDCS therapy is an effective method of Alzheimer's disease therapy that can improve cognitive functions and functioning of patients, both in the short and long term.

Official Title
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Assessment of Effectiveness and Safety of Transcranial Magnetic Stimulation (rTMS) Combined With Transcranial Direct Current Stimulation (tDCS) in Dementia Treatment in Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: Magnetic Stimulator DuoMag
* Device: neuroConn DC-STIMULATOR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with mild to moderate dementia in Alzheimer's disease, diagnosed using DSM-5 criteria. MMSE score from 12 to 26 points ADAS-Cog over 17 points Voluntary consent to participate in the study there is a related person or legal guardian who consented to assist the patient in the course of the study Minimum 8 years of education. It is allowed to use cholinesterase inhibitors and / or memantine for at least 3 months prior to study entry and at a stable dose for at least 60 days prior to study entry. Exclusion Criteria: Severe agitation Intellectual Disability Informed consent is not possible Unstable somatic condition Use of benzodiazepines or barbiturates 2 weeks prior to screening Participation in a clinical trial with coinciding factors within 6 months prior to the start of the trial Seizures Contraindications to rTMS treatment according to the rTMS questionnaire attached to the protocol Contraindications to tDCS treatment according to the tDCS questionnaire attached to the protocol Patients with depression, bipolar, or psychotic disorders, or any other neurological or psychiatric condition (current or past) that the Investigator considers to be interfering with the study Alcoholism or drug addiction as defined by DSM-5 in the last 5 years (addicted for more than a year and or in remission for less than 3 years) Patients with any medical condition that the Investigator considers to be an exclusion criterion from the study

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rTMS stimulation<br>20 sessions of stimulation with increasing intensity, reaching maximum in the 4th session. | Device: Magnetic Stimulator DuoMag<br>* Stimulation of the left dorsolateral prefrontal cortex<br>|
| Active Comparator: tDCS stimulation<br>The stimulation time will be 20 minutes, the current intensity will be 2mA. | Device: neuroConn DC-STIMULATOR<br>* One electrode (anode) will be placed on the left dorsolateral prefrontal cortex, the other (cathode) on the right temporal lobe.<br>|
| Sham Comparator: Sham rTMS stimulation<br>20 sessions of stimulation, but without current. | Device: Magnetic Stimulator DuoMag<br>* Stimulation of the left dorsolateral prefrontal cortex<br>|
| Sham Comparator: Sham tDCS stimulation<br>The stimulation time will be 20 minutes, but without current. | Device: neuroConn DC-STIMULATOR<br>* One electrode (anode) will be placed on the left dorsolateral prefrontal cortex, the other (cathode) on the right temporal lobe.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMSE Scale | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks | 
| ADAS-Cog Scale | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks | 
| NPI Scale | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks | 
| ADCS | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks | 
| GDS | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks | 
| Zarit Burden Interview | Assessment conducted on baseline, up to 1 week after end of the procedure and after 12 weeks. | up to 12 weeks |