Investigating Different Frequencies of Transcranial Electrical Stimulations in Dementia Population

University of Manitoba

Status: Enrolling

Conditions: Dementia

Treatments: Device: Sham; Device: Gamma Transcranial Alternating Current Stimulation (tACS)-Precuneus; Device: Gamma Transcranial Alternating Current Stimulation (tACS); Device: Theta Transcranial Alternating Current Stimulation (tACS); Device: Transcranial Direct Current Stimulation (tDCS); Device: Bilateral DLPFC

Study type: Interventional

Funder types: Other

Identifiers

NCT06547021

HS26590 (B2024:091)

Details and patient eligibility

About

Dementia is a prevalent condition with no known cure. It affects not only the person with dementia but also the family. This study will investigate the effects of applying different transcranial electrical stimulation (tES) waveforms to find the optimal stimulation when paired with cognitive exercise on older adults with dementia. It is a placebo-controlled double-blind study with statistical rigor. In addition, the investigators will investigate technological methods to monitor changes due to the intervention. These include functional near infrared spectroscopy (fNIRS), electroencephalography (EEG), electrovestibulography (EVestG), and balance measurements using accelerometers. fNIRS measures oxygenated and deoxygenated blood flow to the brain and it may help to understand neuronal changes due to intervention. EEG measures the electrical activity of the brain via electrodes placed on the scalp to study the brain's response to different electrical stimulations treatments. EVestG is a non-invasive measure of the vestibuloacoustic system in both background (no motion) and in response to passive whole-body tilt stimuli. We hypothesize there is a direct link between vestibular system deficiencies and Alzheimer's. Lastly, the investigators will measure the effects of electrical stimulation on balance by measuring postural sway using two accelerometers.

This study investigates the effects of transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) with different protocols for frequencies to determine the most effective treatment to improve cognitive abilities and working memory for people with dementia.

The global objective of the proposed study is to investigate the effects of different tES in improving the cognitive status of older adults with dementia, when paired simultaneously with cognitive training. The general objectives include the following:

1. Run a human research randomized and double-blind study to address the global objective of the study with statistical rigor.
2. Investigate the correlation of fNIRS outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictivity to the treatment at baseline.
3. Investigate the effects of different tES on EEG recordings as well as its predictivity to the treatment at baseline.
4. Investigate the effects of different tES on balance for older adults with cognitive impairment.
5. Investigate the correlation of EVestG outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictively to the treatment at baseline.
6. Disseminate the project results and design the next follow up project.

Full description

About 100 participants with either mild cognitive impairment (MCI) or a probable early or moderate dementia type excluding Parkinsonian dementia (as confirmed by their treating physician), will be recruited and tested over the course of this study.

Participants will have the option to choose to do the stimulation and cognitive exercise from home or at Riverview Health Centre. However, all assessments will be completed at Riverview Health Centre. One of the main limitations of human research is the small sample size as recruitment and enrollment of eligible participants especially in dementia population is a major challenge. Thus, a longitudinal study. Each participant will receive all 4 tES protocols in a randomized order while playing cognitive exercises:

1. Personalized gamma tACS
2. Personalized theta tACS
3. tDCS (zero frequency)
4. Sham tES The protocol for all tES treatments will be 4 weeks, 5 days/week (excluding weekends), two 30-min training sessions/day with 15 to 30 min break in between, all tutored either in-person or virtually. Participants will be assessed the week before each new treatment block, within a week of post-treatment and a month after the end of treatment block (follow-up). Between the different tES treatment protocols, 8-week to 20-week washout period will take place with no treatment. The time period for each participant to receive all 4 protocols will be around one year and a half depending on the duration of the washout period. After the participant completes all 4 protocols, there is one more treatment protocol where the participant will receive tACS at the personalized gamma over the regular placement of electrodes (left dorsolateral prefrontal cortex and the reference electrode on the contralateral supraorbital area) for the first 30-min training session and then over the precuneus (one electrode over Pz on the 10-20 EEG system and the other over the right deltoid muscle) during the second 30-min training session. Then the investigators will offer the treatment type (any of the above 5 experimental types) with the highest efficacy for each participant. In other words, the investigators will offer an optimized treatment after the one year and a half.

The eligibility criteria for enrolling individuals into this study are: 50 y<age<95 y, 5<MoCA<24.

Exclusion criteria are any of the followings:

• Being diagnosed with Parkinson's, Parkinsonian dementia, Huntington disease, speech significant aphasia and intellectual disability, major depression/anxiety, bipolar disorder, schizophrenia or any other major mood disorder.
• Having a History of epileptic seizures or epilepsy
• Inability to adequately communicate in English
• Impaired vision or hearing severe enough to impair performance in cognitive tests
• Current substance abuse disorder
• Currently participating in another therapeutic study for dementia

The global objective of the proposed study is to investigate the effects of different tES in improving the cognitive status of older adults with dementia, when paired simultaneously with cognitive training. The general objectives include the following:

1. Run a human research randomized and double-blind study to address the global objective of the study with statistical rigor.
2. Investigate the correlation of fNIRS outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictivity to the treatment at baseline.
3. Investigate the effects of different tES on EEG recordings as well as its predictivity to the treatment at baseline.
4. Investigate the effects of different tES on balance for older adults with cognitive impairment.
5. Investigate the correlation of EVestG outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictively to the treatment at baseline.
6. Disseminate the project results and design the next follow up project.

Enrollment: 100 estimated patients

Sex: All

Ages: 50 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• MoCA score between 5 and 24
• Between the age of 50 and 95 years old

Exclusion criteria

• Being diagnosed with Parkinson's, Parkinsonian dementia, Huntington disease, speech significant aphasia and intellectual disability, major depression/anxiety, bipolar disorder, schizophrenia or any other major mood disorder.
• Having a History of epileptic seizures or epilepsy
• Inability to adequately communicate in English
• Impaired vision or hearing severe enough to impair performance in cognitive tests
• Current substance abuse disorder
• Currently participating in another therapeutic study for dementia
• Change to medication for Alzheimer's disease, dementia, or depression

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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100 participants in 6 patient groups

Transcranial Direct Current Stimulation (tDCS)

Experimental group

Description:

Participants will receive tDCS simultaneously with cognitive exercises for one month every day excluding weekends.

Treatment:

Device: Transcranial Direct Current Stimulation (tDCS)

Gamma Transcranial Alternating Current Stimulation (tACS)

Experimental group

Description:

Participants will receive personalized gamma tACS simultaneously with cognitive exercises for one month every day excluding weekends.

Treatment:

Device: Gamma Transcranial Alternating Current Stimulation (tACS)

Theta Transcranial Alternating Current Stimulation (tACS)

Experimental group

Description:

Participants will receive personalized theta tACS simultaneously with cognitive exercises for one month every day excluding weekends.

Treatment:

Device: Theta Transcranial Alternating Current Stimulation (tACS)

Sham Stimulation

Experimental group

Description:

Participants will receive sham stimulation simultaneously with cognitive exercises for one month every day excluding weekends.

Treatment:

Device: Sham

Gamma Transcranial Alternating Current Stimulation (tACS)-Precuneus

Experimental group

Description:

Participant will receive tACS at the personalized gamma over the regular placement of electrodes (left dorsolateral prefrontal cortex and the reference electrode on the contralateral supraorbital area) for the first 30-min training session and then over the precuneus (one electrode over Pz on the 10-20 EEG system and the other over the right deltoid muscle) during the second 30-min training session.

Treatment:

Device: Gamma Transcranial Alternating Current Stimulation (tACS)-Precuneus

Bilateral DLPFC

Experimental group

Description:

Applying the optimal tES over left and right DLPFC. First 30-min will target the left DLPFC similar to the other arms, and the second 30-min treatment will target tES to the right DLPFC (one electrode over right DLPFC and one electrode over contralateral supraorbital area).

Treatment:

Device: Bilateral DLPFC