High Definition Transcranial Direct Current Stimulation (HD-tDCS) for Early Alzheimer's Disease

Study Overview
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Brief Summary
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To investigate the clinical effect neural mechanism of high-definition transcranial direct current stimulation combined with cognitive training on early AD

Detailed Description
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Upon meeting the inclusion criteria and providing informed consent, each participant will complete a series of cognitive assessments and tDCS at the hospital outpatient clinics or inpatient department. Participants were randomly allocated to anode tDCS group with cognitive training, anode tDCS group and the sham group. There are about 20 participants in each group. Participants were studied using a double-blind design. Study participants and all personnel responsible for the effects of the participants remained masked to allocated condition and allocation parameters. Only tDCS administrators had access to the randomization list; they had minimal contact with the participants, and no role in cognitive assessments. For the first 30 participants, allocation was decided by draw. For the subsequent 30 patients, allocation was according to computer generated random numbers. Each participant would be treated for 10 days in two weeks by HD-tDCS. Before the tDCS, a series of cognitive assessments and neuropsychological tests were obtained by a trained investigator to assess baseline. Each assessment will involve a set of assessment tools, including Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Montreal Cognitive Assessment (MoCA) and associative memory as the primary outcome measure and various other tasks and questionnaires to measure cognition(DS, Stroop test, VFT, SDMT), memory (AVLT, AMT, working memory test), emotion(HAMA-17, HAMD-14, eye-tracking technolodgy), executive function(SST, WSCT, GDT) and stimulation tolerability. All the tests are conducted in two days. The participants had receiving a magnetic resonance imaging scan in multi-modalities, and electroencephalography (EEG) record. Evaluations were conducted one week after treatment and at the end of two weeks of treatment, as well as the Global Index of Safety to assess adverse events of the stimulation. Participants were instructed to focus their answers on the past 7/14 days. The participants had also receiving a battery measure of neuropsychological tests, magnetic resonance imaging scan in multi-modalities, and EEG record. All tests were instructed to finished within 24 hours after the last stimulation. One month and three months after the last stimulation, participants were interviewed to obtain the same assessment as before. They were instructed to focus their answers on the past months.

Official Title
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High Definition Transcranial Direct Current Stimulation (HD-tDCS) for Early Alzheimer's Disease

Conditions
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Transcranial Direct Current Stimulation, Functional Magnetic Resonance Imaging, Early Alzheimer's Disease

Intervention / Treatment
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* Other: HD-tDCS
* Other: computer-based cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject diagnosed with early Alzheimer's disease or related diseases according to NINCDS-ACDRADA criteria. Subjects must have a MMSE score between 10 and 27,indicating mild cognitive impairment or dementia CDR score ≤ 2 Subject under treatment by IAChE for at least 3 months. psychotropic treatments are tolerated if they were administered and unchanged for at least 3 months Exclusion Criteria: CDR > 2 Any history or clinical signs of other severe psychiatric illnesses (like major depression,psychosis or obsessive compulsive disorder). History of head injury,stroke,or other neurologic disease. Organic brain defects on T1 or T2 images. History of seizures or unexplained loss of consciousness. Implanted pacemaker,medication pump,vagal stimulator,deep brain stimulator. Family history of medication refractory epilepsy. History of substance abuse within the last 6 months.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cognitive training<br>Participants will receive Cognitive training daily for two weeks | Other: computer-based cognitive training<br>* Computer-based cognitive training (CCT) is a potentially important tool for individuals at risk of dementia. Cognitive training in healthy older adults and those at risk of dementia has been linked to benefits in cognitive functioning.<br>|
| Active Comparator: Anodal tDCS with Cognitive training<br>Participants will receive anoale tDCS daily and cognitive training for two weeks | Other: HD-tDCS<br>* Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.The respective excitability alterations-enhancement by anodal and reduction by cathodal tDCS-can last for over an hour after the end of stimulation.<br>Other: computer-based cognitive training<br>* Computer-based cognitive training (CCT) is a potentially important tool for individuals at risk of dementia. Cognitive training in healthy older adults and those at risk of dementia has been linked to benefits in cognitive functioning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory improved assessed by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | This is an very common clinical motor estimating scale. including orientation, language, structure, application of concepts, immediate recall of words and recognition of words, with a full score of 70. Higher scores indicate worse symptoms. | changes from baseline at 7,14 days and 4,12 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| special-version working memory | the accuracy and reaction time in working memory task | changes from baseline at 7,14 days and 4,12 weeks post-treatment | 
| Associative Memory | The changes in Associative Memory will constitute the major research outcome measure used to assess response to HD-tDCS. | changes from baseline at 7,14 days and 4,12 weeks post-treatment | 
| MMSE(Mini Mental State Examination) | The full name of MMSE is mini-mental state examination, and the scale consists of 30 subject, include the following seven aspects: time orientation, place orientation,immediate memory,attention and calculation,delay memory,language, visual space.One point is awarded for each question correctly answered during MMSE evaluation. If subject give the wrong answer or don't know answe he/she awarded 0 score, scope of scale score of 0 to 30 points. The higher the score, the better. | changes from baseline at 7,14 days and 4,12 weeks post-treatment | 
| LMT (Logic Memory Test) | The changes in LMT will constitute the secondary research outcome | changes from baseline at 7,14 days and 4,12 weeks post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Definition Transcranial Direct Current Stimulation, Functional Magnetic Resonance Imaging, Neuropsychology, Early Alzheimer's Disease, Working Memory, Alzheimer's Disease Assessment Scale-Cognitive Subscale