40Hz tACS in Treating Cognitive Function and Modulating Neurophysiology of Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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Gamma brain activity is crucial for cognitive function and intra-brain communication. Gamma frequency stimulation via transcranial alternating current stimulation(tACS) might alleviate memory deficits on both animal models of Alzheimer's disease (AD) and clinical trial. The study aims to assess the safety and efficacy of tACS on cognitive function and modulating neurophysiology in patients with AD.

Detailed Description
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Gamma brain activity is crucial for cognitive function and intra-brain communication. Gamma frequency stimulation via transcranial alternating current stimulation(tACS) might alleviate memory deficits on both animal models of Alzheimer's disease (AD) and clinical trial. The study aims to assess the safety and efficacy of tACS on cognitive function and modulating neurophysiology in patients with AD. 40mins 10Hz-tACS for daily consecutive sessions will be given.

Official Title
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40Hz tACS in Treating Cognitive Function and Modulating Neurophysiology of Patients With Alzheimer's Disease: a Triple Blind Randomized Sham-controlled Trial

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: active tACS
* Device: sham tACS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 60- to 90-year-old clinical dementia rating scale (CDR) of 1 or mini-mental state examination (MMSE) score of 18 to 26. Participants were allowed to maintain their anti-dementia medications without changes from at 3 months before and throughout the study. Exclusion Criteria: having contraindications for tACS, e.g., implanted brain medical devices or mental in the head, having arrhythmia and with pacemaker implantation, having history of seizures, having history of intracranial neoplasms or surgery, or severe head injuries or cerebrovascular diseases clinical depression measured by Hamilton depression rating scale score equal and over 17

Ages Eligible for Study
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Minimum Age: 60 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: active tACS<br>40 mins tACS for 10 consecutive daily sessions | Device: active tACS<br>* 40 mins tACS for 10 consecutive daily sessions<br>|
| Sham Comparator: sham tACS<br>40 mins sham tACS for 10 consecutive daily sessions | Device: sham tACS<br>* 40 mins sham tACS for 10 consecutive daily sessions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale, ADAS-Cog | The ADAS-Cog consists of items from the following areas chosen for their sensitivity to Alzheimer's disease: language; memory; praxis; and orientation. The test takes 30-35 minutes to administer and the item scores generally range from 1-5. | Change from baseline, two weeks, and one months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wechsler adult intelligence scale, WAIS-IV, digit span | The Wechsler Adult Intelligence Scale (WAIS) is an IQ test designed to measure intelligence and cognitive ability in adults and older adolescents. It is currently in its fourth edition (WAIS-IV) released in 2008 by Pearson, and is the most widely used IQ test, for both adults and older adolescents, in the world. We used WAIS-IV, digit span subscale, to examine attention among subjects; Digit span was by listening to sequences of numbers orally and to repeat them as heard, in reverse order, and in ascending order. | Change from baseline and two weeks | 
| Wechsler adult intelligence scale, WAIS-IV, digit symbol coding | We used WAIS-IV, digit symbol coding subscale, to examine processing speed among subjects; The digit symbol coding is a paper-and-pencil cognitive test presented on a single sheet of paper that requires a subject to match symbols to numbers according to a key located on the top of the page. The subject copies the symbol into spaces below a row of numbers. The number of correct symbols within the allowed time, usually 90 to 120 seconds, constitutes the score | Change from baseline and two weeks | 
| Wechsler adult intelligence scale, WAIS-IV, vocabulary | We used WAIS-IV, vocabulary subscale, to examine language function among subjects; The vocabulary subtest requires the client to try to define up to 30 words. This subtest assesses the client's understanding of words and reflects: language development, expressive language skills, cultural and educational experiences, ability to use words appropriately, retrieval of information from long-term memory. | Change from baseline and two weeks | 
| Subjective Cognitive Decline Questionnaire: SCD-QMyCog | The SCD-Q is a validated questionnaire that assesses the presence of a subjective cognitive decay in abilities such as memory, attention, language or executive functions. This scale is made up of two parts: MyCog is filled by the subject, TheirCog by the caregiver. Both parts have 24 identical dichotomous questions (yes/no), that evaluate decline for memory performances, language and executive functions in the last 2 years of daily life. The SCD-Q score for MyCog and TheirCog ranges from 0 to 24, with higher scores associated with greater perceived cognitive changes (cut to be classified as SCD = 7). | Change from baseline and two weeks | 
| Neuropsychiatric Inventory (NPI) | The Neuropsychiatric Inventory (NPI) was developed to assess dementia-related behavioral symptoms. The NPI examined 12 sub-domains of behavioral functioning: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, night-time behavioral disturbances and appetite and eating abnormalities | Change from baseline and two weeks | 
| Mini-Mental State Examination, MMSE | A Mini-Mental State Examination (MMSE) is a set of 11 questions that doctors and other healthcare professionals commonly use to check for cognitive impairment (problems with thinking, communication, understanding and memory). The maximum score for the MMSE is 30. A score of 25 or higher is classed as normal. If the score is below 24, the result is usually considered to be abnormal, indicating possible cognitive impairment. | Change from baseline and two weeks | 
| HRV (heart rate variability) | Heart rate variability (HRV) is the physiological phenomenon of variation in the time interval between heartbeats. It is measured by the variation in the beat-to-beat interval. By measuring HRV, it reflects individual's sympathetic and parasympathetic tone. | Change from baseline, after one session, and two weeks | 
| peripheral amyloid beta and tau related markers | Peripheral Amyloid beta and tau protein as risk biomarkers of Alzheimer's disease. We check this to see the influence of tACS on AD-related biomarkers | Change from baseline and two weeks | 
| EEG (electroencephalogram) | An electroencephalogram (EEG) is a recording of brain activity. During this painless test, small sensors are attached to the scalp to pick up the electrical signals produced by the brain. We will check time and/or frequency domain EEG characteristics between those receiving active and sham intervention at different time follow-up points | Change from baseline, after one session, and two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, tACS