Effects of tACS Combined With CCT for Patients With MCI

Not Applicable

• Conditions: Mild Cognitive Impairment
• Interventions: Device: Transcranial Alternating Current Stimulation; Behavioral: Cognitive Training

• Registration Number: NCT04135742
• Lead Sponsor: Shanghai Mental Health Center

Brief Summary

This goal of this study is to explore the effects of transcranial alternating current stimulation(tACS) combined with computerized cognitive training(CCT) on improving cognition for patients with mild cognitive impairment(MCI). The study will recruit 195 patients with MCI. Participants will undergo baseline cognitve assessment, EEG and structural and functional MRI. Participants will be randomized to active tACS+CCT group, sham tACS+CCT group and active tACS+sham CCT group. At the end of the intervention, 3-month, 6-month and 12-month follow-up, all subjects will repeat the baseline assessments.

Detailed Description

tACS is a non-invasive brain stimulation technique that uses a low-intensity alternating current (1 to 2 mA) to apply a sinusoidal current to the scalp, directly interacting with the oscillating cortical activity at a given frequency with a given stimulus intensity. Studies have shown that simultaneous tACS on the left prefrontal lobe and left temporal lobe can significantly improve working memory in healthy older adults. The 40 Hz tACS is gamma oscillation, and more and more studies have pointed out that gamma oscillation regulation disorder is associated with impaired working memory function.CCT can improve the cognition in patients with MCI. We hypothesized that tACS combined with CCT can produce synergistic effects in sensitive brain areas.

Study Timeline

• Study First Submitted: 2019-10-20
• Study First Submitted QC: 2019-10-20
• Study First Posted: 2019-10-23
• Study Start: 2019-11-11
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-06
• Primary Completion: 2023-09-30
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

• (1)age ≥ 60 years old with memory impairment; (2) the memory test scores are lower 1.5 SD than the normal control; (3) in addition to memory impairment, other cognitive functions remain relatively intact or only slightly impaired; (4) normal daily living ability; (5) can not reach the diagnostic criteria for dementia, Clinical Dementia Rating (CDR) is 0.5

Exclusion Criteria

• (1) serious medical diseases such as hypertension, heart disease, severe liver disease, etc.; (2) central nervous system diseases such as cerebrovascular diseases, infectious encephalopathy, brain tumors, etc.; (3) severe depression, schizophrenia and patients who have taken psychotropic substances for a long time; (4) Alzheimer's disease and vascular dementia; (5) history of alcohol dependence and other psychoactive substance abuse; (6) patients with contraindications for magnetic resonance imaging; (7) cannot complete the cognitive function tests for various conditions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
active tACS+ Cognitive Training group	Transcranial Alternating Current Stimulation	Subjects will receive CCT for a period of 3 months, 24 times, twice a week for 20 minutes each time. Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P4). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have 24 tACS sessions for three months, twice a week.The active tACS group will be stimulated with a 2 mA,40Hz current for 20 minutes each time during the stimulation.
active tACS+ Cognitive Training group	Cognitive Training	Subjects will receive CCT for a period of 3 months, 24 times, twice a week for 20 minutes each time. Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P4). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have 24 tACS sessions for three months, twice a week.The active tACS group will be stimulated with a 2 mA,40Hz current for 20 minutes each time during the stimulation.
sham tACS+Cognitive Training group	Cognitive Training	Subjects will receive CCT for a period of 3 months, 24 times, twice a week for 20 minutes each time. Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P4). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have 24 tACS sessions for three months, twice a week.The sham tACS group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.
active tACS+ sham Cognitive Training group	Transcranial Alternating Current Stimulation	Subjects will watch neutral pictures on iPad for a period of 3 months, 24 times, twice a week for 20 minutes each time. Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P4). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have 24 tACS sessions for three months, twice a week.The active tACS group will be stimulated with a 2 mA,40Hz current for 20 minutes each time during the stimulation.

Primary Outcome Measures

Name	Time	Method
Change from baseline RBANS, Color Word Stroop Test (CWST),Visual Reasoning and Trails Making Task.	up to 3 months(end of the intervention)	Global cognition will be assessed by the Repeatable Battery for the Assessment of Neuropsychological Status Total Score (RBANS).CWST mainly can examine the executive function. Visual Reasoning will be assessed by the Cambridge Mental Disorders of the Elderly Examination Visual Reasoning Test.Executive function will be assessed by Trails Making Task.
Neuroimage change from baseline Magnetic Resonance Imaging (MRI)	up to 3 months(end of the intervention)	Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI)
changes in Gamma oscillation intensity (40-80 Hz) over DLPFC	up to 3 months(end of the intervention)	measured by electroencephalogram (EEG)

Secondary Outcome Measures

Name	Time	Method
Changes from baseline RBANS	3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	Global cognition will be assessed by the Repeatable Battery for the Assessment of Neuropsychological Status Total Score (RBANS).
Changes from baseline Visual Reasoning	3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	Visual Reasoning will be assessed by the Cambridge Mental Disorders of the Elderly Examination Visual Reasoning Test.
Changes from baseline in Geriatric Anxiety Inventory (GAI)	up to 3 months(end of the intervention),3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	Geriatric Anxiety Inventory (GAI) will be used to measure neuropsychiatric symptoms.
Changes from baseline Color Word Stroop Test (CWST)	3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	CWST mainly can examine the executive function. There are age-, sex-, and educational year-stratified norms; individuals' z-score can be calculated.
Changes from baseline Trails Making Task	3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	Executive function will be assessed by Trails Making Task.
Changes from baseline Geriatric Depression Scale (GDS)	up to 3 months(end of the intervention),3 months after the end of the intervention,6 months after the end of the intervention and 12 month after the end of the intervention	The Geriatric Depression Scale will be used to measure neuropsychiatric symptoms. It ranges from 0 to 30, and higher value represents a worse outcome.
Neuroimage changes from baseline Magnetic Resonance Imaging (MRI)	6 months after the end of the intervention and 12 month after the end of the intervention	Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI)
Side-effects of tACS	At each stimulation session,up to 3 months.

Trial Locations

Locations (2)

Shanghai Mental Health Center; 🇨🇳 Shanghai, Shanghai, China

Yangpu District Central Hospital; 🇨🇳 Shanghai, China