NCT06783283

TACS to Engage Theta-Gamma Coupling and Enhance Working Memory in Patients With MCI (tACS-MCI)

Transcranial Alternating Current Stimulation to Engage Theta-Gamma Coupling and Enhance Working Memory in Patients With Mild Cognitive Impairment

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Centre for Addiction and Mental Health · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

This study is looking at a new non-invasive brain stimulation methods called transcranial alternating current stimulation (tACS) to see if it can improve working memory and thinking processes in people with Mild Cognitive Impairment (MCI). tACS is a low-risk, non-painful, low electrical current that circulates through the brain of awake participants and stimulates their brain cells. Participants must be 60 years of age and have a diagnosis of mild cognitive impairment. Participants will undergo treatment sessions that range from 1 to 1.5 hours at CAMH, 5 days a week, over a total of 2 weeks. In addition, participants will complete clinical and cognitive assessments and bloodwork at baseline and again after treatment.

Detailed description

Current treatments for Alzheimer's disease dementia (AD) have limited efficacy probably because by the time AD is manifest it is too late to intervene. Thus, discovering interventions that will prevent AD is highly needed. Mild Cognitive Impairment (MCI) is a condition that is considered a pre-stage to AD. In MCI, the frontal part of the brain supports the ability to compensate for memory problems which could delay progression to AD. This compensation is supported by "flexible" thinking which includes the ability to hold and manipulate information in mind for brief periods of time (e.g. doing mental math), also called working memory. Working memory has been shown by us and others to depend on the linking of brain waves across multiple brain waves frequencies. Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation, applied to the scalp, that has been shown to improve this linking of brain waves in healthy older individuals. It has also been shown to enhance working memory in older individuals when this linking is enhanced. The effect of tACS on working memory and linking of brain waves in patients with MCI has not been demonstrated yet. The study investigators propose to study the feasibility and preliminary effects of tACS on TGC and working memory in MCI participants. This proof-of-concept study will test whether tACS engages TGC as a target and, in turn, enhances working memory. Additionally, the investigators will explore the relationship among tACS effects and stress neuroreactivity and neuroimmune/inflammatory response (i.e., the interaction between the nervous system and the immune system), as well as the potential links with working memory. If successful, our project will serve as a model for a larger trial to confirm the ability of tACS to prevent AD over multiple years of follow-up. Objective 1: To determine the feasibility of tACS in older individuals with MCI. The investigators will examine recruitment and retention. Hypothesis 1a: At least 30% of screened participants will agree and be eligible to receive the intervention they are assigned to, i.e., tACS. Hypothesis 1b: At least 70% of participants will attend at least 80% of their treatment sessions. Objective 2: To determine TGC engagement in response to tACS. The investigators will assess whether TGC increases in response to tACS. Hypothesis 2: Participants randomized to tACS will experience higher increase in TGC than those randomized to sham-tACS. Objective 3: To determine change in working memory in response to tACS, and whether changes in TGC mediate changes in N-back performance with 2-back d' being the primary N-back outcome measure. Hypothesis 3a: Participants randomized to tACS will experience more improvement on N-back from baseline following the intervention than those randomized to sham-tACS. Hypothesis 3b: Across all participants, change in TGC will mediate change in N-back performance. Exploratory Objective 4: To explore the relationships among tACS effects and stress neuroreactivity and neuroimmune/inflammatory response, as well as the potential links with working memory. Exploratory Hypothesis 4a: Baseline measure of stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) will moderate response to tACS vs. sham-tACS. Exploratory Hypothesis 4b: Baseline measure of neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP / IL-1β, IL-6, CRP, and TNF-α) will moderate response to tACS vs. sham-tACS. Exploratory Hypothesis 4c: Participants randomized to tACS will experience better stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) from baseline following the intervention than those randomized to sham-tACS. Exploratory Hypothesis 4d: Participants randomized to tACS will experience better neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP / IL-1β, IL-6, CRP, and TNF-α) from baseline following the intervention than those randomized to sham-tACS. Exploratory Mediation Hypothesis: Across all participants, changes in stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) and neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP /I L-1β, IL-6, CRP, and TNF-α) will mediate change in TGC, N-back performance, and working memory.

Conditions

• Mild Cognitive Impairment (MCI)

Interventions

Type	Name	Description
DEVICE	Transcranial Alternating Current Stimulation	Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation that will be used to stimulate the dorsolateral prefrontal cortex (dlPFC) and temporal cortices and in turn enhance Theta-Gamma Coupling (TGC) and working memory in Mild Cognitive Impairment (MCI). Each participant will receive daily stimulation for 10 days. To deliver the tACS, multiple electrodes embedded in a cap placed on the participant's head. Sham-tACS will follow the same procedure.
DEVICE	Sham tACS	During sham-tACS, the device will ramp up to the desired intensity over 60 seconds, and then will immediately ramp down, and the stimulation will be shut off, until the end of the session. At the end of the session, the device will again ramp up for 60 seconds and then ramp down. Sham-tACS will also target dlPFC and temporal cortices (similar to active). Each participant will receive daily sham-tACS for 10 days. To deliver the sham-tACS, multiple electrodes will be embedded in a cap placed on the participant's head.

Timeline

• Start date: 2025-01-02
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2025-01-20
• Last updated: 2026-04-13

Locations

1 site across 1 country: Canada