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

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

Study Overview

• Status: Recruiting
• Conditions: Early Alzheimer's Disease; Functional Magnetic Resonance Imaging; Transcranial Direct Current Stimulation
• Intervention / Treatment: Other: computer-based cognitive training; Other: Sham tDCS; Other: HD-tDCS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xingqi Wu, M.D.; Phone Number: +86 18788836237; Email: wuxingqi09@163.com
• Study Contact Backup: Name: Kai Wang, PhD; Phone Number: +86-0551-62922263; Email: wangkai1964@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230032
      • Recruiting
      • Anhui Medical University
      • Contact: Xingqi Wu, M.D.; Phone Number: +8618788836237; Email: wuxingqi09@163.com
      • Contact: Guixian Xiao; Phone Number: +8617705605378; Email: xiaoguixian1002@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anodal tDCS with Cognitive training; Participants will receive anoale tDCS daily and cognitive training for two weeks	Other: computer-based cognitive training; Computer-based cognitive training (CCT) is a potentially important tool for individuals at risk of dementia. This trial will employ a computerized multi-domain adaptive training program. This program and training model have been demonstrated to be effective and beneficial in patients with vascular cognitive impairment. In the CCT intervention group, participants will undergo 2 weeks of computerized, multi-domain, adaptive training. The training domains include processing speed, attention, perception, long-term memory, working memory, calculation, executive control, reasoning, and problem-solving. Task rigor varies across domains and determines task grouping. Participants are required to complete 30 minutes of daily training(one session each of six 5-minute tasks).; Other: HD-tDCS; Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.HD-tDCS was administered using the Soterix 1×1 tDCS Low-Intensity Stimulator and the Soterix 4×1 Adapter. The selection of the electrode montage was based on computational models generating simulated current topography using HD Explore, which demonstrated good current distribution in the left dorsolateral prefrontal cortex (DLPFC). For left DLPFC stimulation, the anodal electrode was placed at the F3 position (using the International 10-20 EEG system), and the 4 return electrodes (cathodes) were placed at positions AFz, FCz, F7, and C5 (4-6 cm from the anode). The center position CZ was aligned with the vertex of the head. During anodal DLPFC stimulation, participants received stimulation at 2 mA for 30 minutes, including a 30-second ramp-up period at the start and a 30-second ramp-down period at the end.
Sham Comparator: Sham-Anode tDCS&Cognitive training; Participants will receive Cognitive training+Sham tDCS daily for two weeks	Other: computer-based cognitive training; Computer-based cognitive training (CCT) is a potentially important tool for individuals at risk of dementia. This trial will employ a computerized multi-domain adaptive training program. This program and training model have been demonstrated to be effective and beneficial in patients with vascular cognitive impairment. In the CCT intervention group, participants will undergo 2 weeks of computerized, multi-domain, adaptive training. The training domains include processing speed, attention, perception, long-term memory, working memory, calculation, executive control, reasoning, and problem-solving. Task rigor varies across domains and determines task grouping. Participants are required to complete 30 minutes of daily training(one session each of six 5-minute tasks).; Other: Sham tDCS; Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.HD-tDCS was administered using the Soterix 1×1 tDCS Low-Intensity Stimulator and the Soterix 4×1 Adapter. The selection of the electrode montage was based on computational models generating simulated current topography using HD Explore, which demonstrated good current distribution in the left dorsolateral prefrontal cortex (DLPFC). For left DLPFC stimulation, the anodal electrode was placed at the F3 position (using the International 10-20 EEG system), and the 4 return electrodes (cathodes) were placed at positions AFz, FCz, F7, and C5 (4-6 cm from the anode). The center position CZ was aligned with the vertex of the head. For sham stimulation, participants received only the initial 30-second ramp-up to 2 mA, after which stimulation was immediately terminated.
Active Comparator: Anodal tDCS without Cognitive training; Participants will receive anoale tDCS daily without cognitive training for two weeks	Other: HD-tDCS; Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak direct currents.HD-tDCS was administered using the Soterix 1×1 tDCS Low-Intensity Stimulator and the Soterix 4×1 Adapter. The selection of the electrode montage was based on computational models generating simulated current topography using HD Explore, which demonstrated good current distribution in the left dorsolateral prefrontal cortex (DLPFC). For left DLPFC stimulation, the anodal electrode was placed at the F3 position (using the International 10-20 EEG system), and the 4 return electrodes (cathodes) were placed at positions AFz, FCz, F7, and C5 (4-6 cm from the anode). The center position CZ was aligned with the vertex of the head. During anodal DLPFC stimulation, participants received stimulation at 2 mA for 30 minutes, including a 30-second ramp-up period at the start and a 30-second ramp-down period at the end.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DST (Digital Span Test; Forward and Backward)	The changes in DST will constitute the other research outcome.	changes from baseline at 14 days and 4,12 weeks post-treatment
TMT (Trail Making Test)	The Trail Making Test (TMT) is divided into two parts, part A and part B. Part A requires the subject to connect 25 Numbers on the paper in sequence, and part B requires the subject to connect 25 Numbers of different colors alternately in sequence. The time it takes for the subject to complete all the Numbers is the subject's final score.	changes from baseline at 14 days and 4,12 weeks post-treatment
HAMD (Hamilton Depression Scale)	The changes in HAMD will constitute the other research outcome. The examination content consists of 17 questions (about 10 minutes), with a full score of 52. The higher the score, the more severe the depressive symptoms are.	changes from baseline at 14 days and 4,12 weeks post-treatment
HAMA (Hamilton Anxiety Scale)	The changes in HAMD will constitute the other research outcome. The examination content consists of 14 questions (about 10 minutes), with a full score of 56. The higher the score, the more severe the anxiety symptoms are.	changes from baseline at 14 days and 4,12 weeks post-treatment
NPI (Neuropsychiatric Inventory)	The changes in HAMD will constitute the other research outcome.	changes from baseline at 14 days and 4,12 weeks post-treatment
MRI measures	Multimodal magnetic resonance data were acquired, including structural phase magnetic resonance and rest state magnetic resonance.	changes from baseline at 14 days and 4,12 weeks post-treatment
changes in Montreal Cognitive Assessment (MoCA)	MoCA was developed by Nasreddine et al. based on clinical experience and reference to the MMSE cognitive items and scores, and the final version was finalized in November 2004. We adopted a localized version (Mandarin version，includes 2 alternative versions) in line with the Chinese cultural background.It includes 11 inspection items in 8 cognitive fields, including visual structure skills, executive function, naming, attention and calculation, language, abstract thinking, memory, and orientation. With a total score of 30 or more than 26, it is normal. Anyone who has been education for less than 12 years will need to add one point to his final score.	changes from baseline at 14 days and 4,12 weeks post-treatment
GDS(Geriatric depression scale)	The Geriatric Depression Scale (GDS) was created in 1982 by Brank et al. and is dedicated to screening for depression in the elderly. The most suitable feelings for the elderly in the past week were evaluated.There are 30 items in the scale, the total score is 30 points. The higher the score, the more obvious the depressive symptoms. It is generally considered that less than 10 points is normal.	changes from baseline at 14 days and 4,12 weeks post-treatment
JLOT(Judgment of line Judgment of line orientation test orientation test)	The JLOT test was determined by Benton et al. in 1994. There are two versions of H and V. The difference is that the order in which the pictures are presented is different. Each version contains 35 images, of which the official test consists of 30 images, and the other 5 images are for the participants to learn. The final score is the correct number of subjects to answer, the full score is 30 points, the higher the score, the better the space perception ability of the subject.	changes from baseline at 14 days and 4,12 weeks post-treatment
HVOT(Hooper visual organization test Hooper visual organization test)	The changes in HVOT(Hooper visual organization test Hooper visual organization test) will constitute assess response to rTMS the secondary research outcome measure.HVOT is a cognitive test used to evaluate the perceived structure of the subject. It consists of 30 items，and each question is 1 point and the total score is 30 points. The final score is the correct number of subjects to answer, the full score is 30 points, the higher the score, the better the space perception ability of the subject.	changes from baseline at 14 days and 4,12 weeks post-treatment
The Stroop color test	The Stroop color word test was developed by Stroop in 1935 and is used to evaluate the attention function of the subject. The subject is required to correctly read the target color on the stimulus card and record the completion time. The final completion time is the score of the participant. The shorter the time used, the better the performance of the subjects.	changes from baseline at 14 days and 4,12 weeks post-treatment

Collaborators and Investigators

• Sponsor: Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 18, 2020
• First Submitted That Met QC Criteria: October 18, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Functional Magnetic Resonance Imaging; Neuropsychology; Working Memory; Early Alzheimer's Disease; High Definition Transcranial Direct Current Stimulation; Alzheimer's Disease Assessment Scale-Cognitive Subscale
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: AH med university2018913

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No