Combined tDCS and Cognitive Training in Alzheimer's

NCT06861231 | Enrolling By Invitation

• 1 other identifier: 2601758
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The General Objective of the study is to evaluate the short- and long-term efficacy of combining transcranial Direct Current Stimulation (tDCS) and cognitive training (CT) in patients with mild cognitive impairment and early-stage Alzheimer's disease. A randomized, double-blind, placebo-controlled design will be applied. An inter-subject design with two groups will be used: a. Active tDCS + concurrent CT and b. Sham tDCS + concurrent CT. Evaluations will be taken at pre-test, post-test, and follow-up one month later. The hypothesis comparing active and sham tDCS with concurrent CT is that, although both groups should improve due to concurrent CT, it is expected that the active tDCS group will show significantly greater improvements in post-treatment. Additionally, these improvements should be maintained in the long-term follow-up in the active tDCS group, while in the sham tDCS group, a return to baseline is expected in the follow-up measures. Transcranial Direct Current Stimulation (tDCS): HDC stimulators (Newronika TM, Milan, Italy) will be used. For active stimulation, the current intensity will be constant at 2 mA, with a stimulation time of 20 minutes daily for 12 days, and an initial and final ramp of 30 seconds. For the placebo group, current will only be applied during the initial and final ramps to generate the sensation of active stimulation. A neoprene cap with carbon rubber electrodes and sponges soaked in saline solution (5 x 5 cm) will be used. The anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode over the right supraorbital area (rSO). Cognitive Training (CT): The CT will consist of 12 sessions of 50 minutes each, based on tasks involving executive functions and memory, including categorization, answering questions, short stories, problem-solving, recalling autobiographical moments, planning simple tasks, and schedule analysis.

Conditions

Prodromal Alzheimer's Disease

Keywords

Cognitive impairment; Transcranial direct current stimulation; Cognitive training

Outcome Measures

Primary Outcomes (1)

• Mini-Mental State Examination (MMSE)

  The Mini-Mental State Examination (MMSE) was used as an index of global cognitive functioning; the maximum score is 30 points. This test was designed to estimate the existence and severity of cognitive impairment. Participants with scores equal to or below 23 will be considered cognitive deficient. Post-intervention minus baseline. Difference score range is (-30 to 30) with positive scores reflecting improvement.

  Baseline to approximately 6 weeks

Secondary Outcomes (2)

• Direct and inverse digits of the Wechsler Intelligence Scale for Adults-III

  Baseline to approximately 6 weeks

• Complutense Verbal Learning Test (TAVEC) - Memory

  Baseline to approximately 6 weeks

Other Outcomes (2)

• Memory Alteration Test (M@T)- Cognitive Impairment

  Baseline to approximately 6 weeks

• Barcelona Test (BT) - Ability to Access and Recall Elements From the Lexical and Semantic Store

  Baseline to approximately 6 weeks

Study Arms (2)

tDCS active and cognitive training

EXPERIMENTAL

tDCS: HDC stimulator will be used. For active stimulation, it will be programmed with a constant current intensity of 2mA and a stimulation time of 20 minutes daily for 12 days, with an initial and final ramp of 30 seconds. A neoprene cap based on the international 10-10 EEG system will be used for current passage to the skull. The electrodes will have two sponges (5 x 5 cm) soaked in saline solution for contact with the skull. The anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode will be placed over the right supraorbital area (rSO). Cognitive training consists of a total of 12 sessions lasting 50 minutes each. These sessions will primarily focus on tasks involving executive functions and memory for a similar duration in each session. At the beginning of the sessions, instructions will be explained, followed by handing out activity sheets. The emphasis will not be on the outcome but on the cognitive activation process.

Device: Transcraneal Direct Current Stimulation (tDCS)- Active; Behavioral: Cognitive Training (CT)

tDCS sham and cognitive training

ACTIVE COMPARATOR

For the active comparator group, the stimulator will be programmed so that patients will receive direct current only during the ramps to generate the sensation of the current. Thus, it will enter a current pause after completing the initial ramp and will be activated in the final seconds during the final ramp. The cognitive training program will have the same characteristics as in the experimental group.

Device: Transcranial Direct Current Stimulation (tDCS)- Sham; Behavioral: Cognitive Training (CT)

Interventions

Transcraneal Direct Current Stimulation (tDCS)- Active DEVICE

The stimulation will use a neoprene cap with carbon rubber electrodes and sponges soaked in saline solution (5x5 cm). The anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode over the right supraorbital area (rSO). Constant current intensity of 2mA and a stimulation time of 20 minutes per day for 12 days will be applied, with an initial and final ramp of 30 seconds.

tDCS active and cognitive training

Transcranial Direct Current Stimulation (tDCS)- Sham DEVICE

Participants assigned to the sham tDCS group will also receive 12 home-based sessions of 20 minutes each. However, to mimic the sensation of active stimulation without delivering therapeutic current, the stimulator will only apply current during the initial and final 30-second ramp periods. The device will remain on for 20 minutes, but no current will be applied after the first ramp, simulating an active procedure without physiological effect.

tDCS sham and cognitive training

Cognitive Training (CT) BEHAVIORAL

All participants will complete 12 home-based cognitive training sessions, each lasting 50 minutes. The training will include structured tasks focused on executive function and memory, such as categorization, problem-solving, autobiographical recall, planning, and schedule analysis. Instructions will be provided at the start of each session, and participants will work independently or with caregiver support.

tDCS active and cognitive training; tDCS sham and cognitive training

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prodromal Alzheimer's disease: score equal to or higher than 23 points on the MMSE and scores equal to level 3 on the Global Deterioration Scale (GDS).
• Initial Alzheimer's disease: score equal to or higher than 18 points on the MMSE and scores equal to level 4 on the Global Deterioration Scale (GDS).

You may not qualify if:

• subjects with contraindications to tDCS (metal implants, intracranial, intracranial hypertension), significant cerebrovascular disease or severe psychiatric symptoms.

Sponsors & Collaborators

• University of Valencia: lead

Study Sites (1)

Universidad de Valencia

Valencia, 46010, Spain

Location

Related Publications (6)

• Melendez JC, Satorres E, Pitarque A, Delhom I, Real E, Escudero J. Effectiveness of tDCS at Improving Recognition and Reducing False Memories in Older Adults. Int J Environ Res Public Health. 2021 Feb 1;18(3):1317. doi: 10.3390/ijerph18031317.

  PMID: 33535690 RESULT

• Satorres E, Escudero Torrella J, Real E, Pitarque A, Delhom I, Melendez JC. Home-based transcranial direct current stimulation in mild neurocognitive disorder due to possible Alzheimer's disease. A randomised, single-blind, controlled-placebo study. Front Psychol. 2023 Jan 3;13:1071737. doi: 10.3389/fpsyg.2022.1071737. eCollection 2022.

  PMID: 36660288 RESULT

• Satorres E, Melendez JC, Pitarque A, Real E, Abella M, Escudero J. Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults. Int J Environ Res Public Health. 2022 Oct 5;19(19):12716. doi: 10.3390/ijerph191912716.

  PMID: 36232016 RESULT

• Hill AT, Fitzgerald PB, Hoy KE. Effects of Anodal Transcranial Direct Current Stimulation on Working Memory: A Systematic Review and Meta-Analysis of Findings From Healthy and Neuropsychiatric Populations. Brain Stimul. 2016 Mar-Apr;9(2):197-208. doi: 10.1016/j.brs.2015.10.006. Epub 2015 Oct 23.

  PMID: 26597929 RESULT

• Bahar-Fuchs A, Martyr A, Goh AM, Sabates J, Clare L. Cognitive training for people with mild to moderate dementia. Cochrane Database Syst Rev. 2019 Mar 25;3(3):CD013069. doi: 10.1002/14651858.CD013069.pub2.

  PMID: 30909318 RESULT

• Gates NJ, Vernooij RW, Di Nisio M, Karim S, March E, Martinez G, Rutjes AW. Computerised cognitive training for preventing dementia in people with mild cognitive impairment. Cochrane Database Syst Rev. 2019 Mar 13;3(3):CD012279. doi: 10.1002/14651858.CD012279.pub2.

  PMID: 30864747 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Transcranial Direct Current Stimulation; Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Juan C Melendez, PhD

  University of Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychology

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 6, 2025
• Study Start: October 4, 2024
• Primary Completion: September 15, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)