NCT04599764

Brief Summary

This completed randomized trial evaluated the clinical and neural effects of high-definition transcranial direct current stimulation (HD-tDCS) combined with computerized cognitive training in patients with Alzheimer's disease. Participants were assigned to active HD-tDCS plus computerized cognitive training, computerized cognitive training control, or active HD-tDCS control. The study assessed whether combined neuromodulation and cognitive training produced greater cognitive and clinical benefit than either component condition, and whether treatment-related benefit was associated with changes in brain network organization.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jun 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2020

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

October 18, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

October 23, 2020

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

June 11, 2026

Status Verified

June 1, 2026

Enrollment Period

5.5 years

First QC Date

October 18, 2020

Last Update Submit

June 9, 2026

Conditions

Keywords

High Definition Transcranial Direct Current StimulationFunctional Magnetic Resonance ImagingNeuropsychologyEarly Alzheimer's DiseaseWorking MemoryAlzheimer's Disease Assessment Scale-Cognitive Subscale

Outcome Measures

Primary Outcomes (1)

  • Changes 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 14 days and 12 weeks post-treatment

Secondary Outcomes (4)

  • special-version working memory

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • Associative Memory

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • MMSE(Mini Mental State Examination)

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • LMT (Logic Memory Test)

    changes from baseline at 7,14 days and 4,12 weeks post-treatment

Other Outcomes (11)

  • DST (Digital Span Test; Forward and Backward)

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • TMT (Trail Making Test)

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • HAMD (Hamilton Depression Scale)

    changes from baseline at 14 days and 4,12 weeks post-treatment

  • +8 more other outcomes

Study Arms (3)

Sham-Anode tDCS & Computerized cognitive training

SHAM COMPARATOR

Participants will receive Computerized cognitive training+Sham tDCS daily for two weeks

Other: computer-based cognitive trainingOther: Sham tDCS

Anodal tDCS with Computerized cognitive training

ACTIVE COMPARATOR

Participants will receive anoale tDCS daily and Computerized cognitive training for two weeks

Other: HD-tDCSOther: computer-based cognitive training

Anodal tDCS with Control Cognitive training

ACTIVE COMPARATOR

Participants will receive anoale tDCS daily with control cognitive training for two weeks

Other: HD-tDCSBehavioral: Control cognitive training

Interventions

HD-tDCSOTHER

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.

Anodal tDCS with Computerized cognitive trainingAnodal tDCS with Control 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).

Anodal tDCS with Computerized cognitive trainingSham-Anode tDCS & Computerized cognitive training

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.

Sham-Anode tDCS & Computerized cognitive training

Control cognitive training consisted of a structured, computer-based cognitive activity matched to the adaptive computerized cognitive training program for session duration, screen exposure, task instructions, and participant contact. The control tasks used fixed or minimally adaptive task difficulty and did not provide individualized, performance-based progression. This condition was designed to control for nonspecific effects of computer use, task engagement, therapist contact, and repeated cognitive activity, while minimizing the adaptive cognitive-training component.

Anodal tDCS with Control Cognitive training

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Anhui Medical University

Hefei, Anhui, 230032, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Caregivers, subjects, and evaluators remain blind
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of medical psychological department, Anhui Medical University

Study Record Dates

First Submitted

October 18, 2020

First Posted

October 23, 2020

Study Start

June 1, 2020

Primary Completion

December 1, 2025

Study Completion

December 1, 2025

Last Updated

June 11, 2026

Record last verified: 2026-06

Locations