Non-invasive Neurostimulation as a Tool for Diagnostics and Management for Neurodegenerative Diseases

Study Overview
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Brief Summary
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Double blinded, sham-controlled, randomized trial on repeated transcranial alternating current brain stimulation (tACS) in neurodegenerative diseases. The investigators will evaluate whether a 4-times daily repeated stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with neurodegenerative diseases, including dementia with Lewy Bodies, Alzheimer's disease, idiopathic normal pressure hydrocephalus and Frontotemporal dementia.

Detailed Description
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Double blinded, sham-controlled, randomized trial on repeated transcranial alternating current brain stimulation (tACS) in neurodegenerative diseases. The investigators will evaluate whether a 4-times daily repeated stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with neurodegenerative diseases, including dementia with Lewy Bodies, Alzheimer's disease, idiopathic normal pressure hydrocephalus and Frontotemporal dementia.

Official Title
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Non-invasive Neurostimulation as a Tool for Diagnostics and Management for Neurodegenerative Diseases

Conditions
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Alzheimer Disease, Frontotemporal Dementia, Dementia With Lewy Bodies

Intervention / Treatment
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* Device: Gamma tACS (40 Hz) over the superior parietal cortex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild Cognitive Impairment due to Alzheimer's disease Dementia with Lewy Bodies Frontotemporal dementia Idiopathic normal pressure hydrocephalus (iNPH) Exclusion Criteria: History of seizures Pregnancy Metal implants in the head (except dental fillings) Electronic implants (i.e. pace-maker, implanted medical pump) Age <18 years

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real tACS<br>Four sessions (once a day, during four consecutive days) of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus) | Device: Gamma tACS (40 Hz) over the superior parietal cortex<br>* Single session of gamma tACS (40 Hz) over the superior parietal cortex<br>|
| Placebo Comparator: Sham tACS<br>Four sessions of sham tACS (once a day, during four consecutive days) over the superior parietal cortex (Precuneus) | Device: Gamma tACS (40 Hz) over the superior parietal cortex<br>* Single session of gamma tACS (40 Hz) over the superior parietal cortex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Rey Auditory Verbal Learning Test score | Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The examiner reads aloud 15 unrelated words and the participant is asked to recall the words after each of the five trials. After a 15 minute delay, the participant is asked again to recall the words. The score ranges from 0 (worst performance) to 75 (best performance). | Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention | 
| Changes in Rey Auditory Verbal Learning Test, recognition | Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. After a 15 minute delay, the participant is asked to recognise the original 15 words intermixed with 31 distractor words. The score of the recognition part ranges from 0 (worst performance) to 46 (best performance). | Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention | 
| Changes in orientation to time and place (MMSE questions 1-10) | 10 questions about the orientation. The score ranges from 0 (worse performance) to 10 (best performance). | Baseline (immediately before the intervention), immediately after the last intervention, 4 weeks after the last intervention | 
| Changes in Trail Making A & B tests | TMT A & B tests. Time to perform set is recorded. | Baseline (immediately before the intervention), immediately after the 4th intervention, 4 weeks after the last intervention | 
| Changes in INECO Frontal Screening test | Test battery assessing frontal lobe functions. The score ranges from 0 (worse performance) to 30 (best performance) | Baseline (immediately before the intervention), immediately after the 4th intervention, 4 weeks after the last intervention | 
| Changes in phonemic fluency | Person is requested to provide as many words as possible starting with certain letter. The score is the sum of all acceptable words produced in one minute. | Baseline (immediately before the intervention), immediately after the first intervention, immediately after the 4th intervention, 4 weeks after the last intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SAI measurements | By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic neurotransmission. | Baseline (immediately before the intervention), immediately after the last intervention | 
| Change in SICI measurements | By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short interval intracortical inhibition (SICI), which is a marker of gabaergic neurotransmission. | Baseline (immediately before the intervention), immediately after the last intervention | 
| Change in ICF measurements | By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on intracortical facilitation (ICF), which is a marker of glutamatergic neurotransmission. | Baseline (immediately before the intervention), immediately after the last intervention |