High Definition Transcranial Direct Current Stimulation (HD-tDCS) in Patients With Mild Cognitive Impairment

Study Overview
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Brief Summary
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The study aimed to investigate whether high definition transcranial direct current stimulation (HD-tDCS) could benefit global cognitive function and sub-domains of cognition (visual/verbal/working memory, executive function, attention, processing speed, language, and frontal lobe function), mood (depression and anxiety), and subjective memory impairment in patients with mild cognitive impairment.

Detailed Description
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Transcranial direct current stimulation (tDCS), a novel, non-invasive and safe neuro-modulating technique, has been developed as a new therapeutic option for neuropsychiatric disorders. It encompasses the induction of a relatively weak constant current flow through the cerebral cortex via scalp electrodes. Dependent on stimulation polarity, this results in a modulation of cortical excitability and spontaneous neural activity. Compared with tDCS, high-definition transcranial direct current stimulation (HD-tDCS) is highly focal and can specifically modulate cortical activity within the region confined by its 4 x 1 ring of elctrodes, such that the targeted region becomes more amenable to neuroplastic change. Studies have suggested that tDCS improve cognition, including memory recall, verbal fluency and executive function. Yet, there is not HD-tDCS study on MCI. The purpose of this study is to examine whether HD-tDCS could benefit global cognitive function and sub-domains of cognition (visual/verbal/working memory, executive function, attention, processing speed, language, and frontal lobe function), mood (depression and anxiety), and subjective memory impairment in patients with mild cognitive impairment.

Official Title
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The Effect of High Definition Transcranial Direct Current Stimulation (HD-tDCS) on Cognitive Function in Patients With Mild Cognitive Impairment: a Randomized, Triple-blind, Sham-controlled, Pilot Study

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Device: HD-tDCS treatment
* Device: sham (placebo) HD-tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 65 to 85 years mild cognitive impairment right handed Exclusion Criteria: Having epilepsy, severe physical illness, any current psychiatric comorbidity or history of substance dependence Having contraindications for transcranial electrical/magnetic stimulation. Having intracranial metal foreign bodies Having a history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases Receiving psychotropic agents such as antipsychotic, antidepressant, benzodiazepam and anxiolytics etc.

Ages Eligible for Study
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Minimum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2 milli Amp dose of HD-tDCS treatment<br>2 milli Amp dose of HD-tDCS treatment for for 20 minutes, for 5 consecutive twice daily sessions | Device: HD-tDCS treatment<br>* 2 milli Amp dose of HD-tDCS treatment for for 20 minutes, for 5 consecutive twice daily sessions<br>|
| Sham Comparator: Sham (placebo) dose of HD-tDCS treatment<br>Sham (placebo) dose of HD-tDCS treatment for 20 minutes, for 5 consecutive twice daily sessions | Device: sham (placebo) HD-tDCS<br>* Participants will receive sham (placebo) HD-tDCS for 20 minutes, for 5 consecutive twice daily sessions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Abilities Screening Instrument, CASI | The Cognitive Abilities Screening Instrument (CASI) is a cognitive test screening for dementia, in monitoring the disease progression, and in providing profiles of cognitive impairment by examining abilities on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment with score ranges of 0 to 100, respectively. | Change from baseline after one week, one and three months | 
| Wechsler Memory Scale-third edition (WMS III) - verbal paired associates I and II | For assessing verbal memory by assessing recall memory for orally presented word pairs that have been previously learned (verbal paired associates I); assessing ability to recall associations from Verbal Paired Associates I after a 30-minute delay, as well as assessing recognition of word pairs (verbal paired associates II). | Change from baseline after one week, one and three months | 
| Wechsler Memory Scale-third edition (WMS III) - visual reproduction I and II | For assessing visual memory function by assessing ability to reproduce difficult-to-verbalize designs after a brief exposure (visual reproduction I); assessing ability to recall the designs presented in Visual Reproduction I after a 30-minute delay, as well as specific sub-subtests to assess recognition of correct figures from nontarget figures, copying of figures to assess visual perception abilities, and a subtest to analyze discrimination abilities (visual reproduction II). | Change from baseline after one week, one and three months | 
| Wisconsin card sorting test | for assessing executive function | Change from baseline after one week, one and three months | 
| Frontal assessment battery, FAB | The FAB is a brief tool that can be used at the bedside or in a clinic setting to assist frontal function of subjects. Total score is from a maximum of 18, higher scores indicating better performance. The scales consist similarities (conceptualization), lexical fluency (mental flexibility), motor series Luria test (programming), conflicting instructions (sensitivity to interference), Go-No Go (inhibitory control), prehension behaviour (environmental autonomy). | Change from baseline after one week, one and three months | 
| Wechsler adult intelligence scale four edition, 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 after one week, one and three months | 
| Wechsler adult intelligence scale four edition, 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 after one week, one and three months | 
| Wechsler adult intelligence scale four edition, 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 after one week, one and three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck depression inventory (BDI-II) | The BDI-II was a 1996 revision of the BDI. Participants were asked to rate how they have been feeling for the past two weeks. BDI-II also contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs used as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression. | Change from baseline after one week, one and three months | 
| Beck anxiety inventory (BAI) | The Beck Anxiety Inventory (BAI), created by Aaron T. Beck and other colleagues, is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults. The BAI contains 21 questions, each answer being scored on a scale value of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms. The standardized cutoffs are as follows: 0-7: minimal anxiety; 8-15: mild anxiety; 16-25: moderate anxiety; 26-63: severe anxiety. | Change from baseline after one week, one and three months | 
| Subjective Cognitive Decline Questionnaire (SCD-Q MyCog) | 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 after one week, one and three months |