Gamma tACS in Alzheimer's Disease

Study Overview
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Brief Summary
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Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease.

Detailed Description
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Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease. Subjects will be randomized in two groups, one receiving a single treatment with gamma tACS (40 Hz) first and the other receiving sham stimulation. After one week the treatments will be exchanged. Patients will be evaluated with neuropsychological tests and neurophysiological measures of cholinergic transmission.

Official Title
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Interventional Cross-over Study to Evaluate the Efficacy on Cognitive Performance of Alternating Current Brain Stimulation (tACS) in Patients Suffering From Neurodegenerative Diseases

Conditions
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Alzheimer Disease

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 (according to Albert et al., Alzheimers Dement 2011). Exclusion Criteria: Cerebrovascular disorders, previous stroke, hydrocephalus, and intra-cranial mass documented by MRI. History of traumatic brain injury or other neurological diseases. Serious medical illness other than FTD 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: real tACS<br>Single session 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>Single session of sham tACS 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 scores | 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 score ranges from 0 (worse performance) to 15 (best performance). | Baseline (immediately before the intervention) - Immediately after the intervention | 
| Changes in Face-Name Associative Memory Test scores | The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance). | During the 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 transmission. | Baseline (immediately before the intervention) - Immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, transcranial Alternating Current Stimulation, tACS, Gamma stimulation