Comparison of Two Non-invasive Neuromodulation Techniques as Synergistic Therapy to Cognitive Stimulation in Amnestic Mild Cognitive Impairment (aMCI)

Summary

This is a comparative, double-blind, randomized controlled clinical trial for people with Amnestic Mild Cognitive Impairment. The investigators will compare the effects of two non-invasive neuromodulation techniques (Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation) combined with cognitive stimulation. These non-invasive neuromodulating techniques will be applied as a treatment alternative to be able to compare non-invasive techniques with cognitive stimulation CS alone, taking into account clinical and neuropsychological evaluations in addition to: 1) the known clinical risk factors (physical activity, comorbidities treatment, etc.) that allow the investigators to characterize the participants; 2) characterize the participants with genetic biomarkers using the APOE4, CR1, COMT, TREM2 and ABCA7 genotype; 3) document the biological effects related to neurogenesis from olfactory epithelial neural progenitor cells and solubles factors of serum; 4) use hippocampal volume, cortical thickness of the medial temporal cortex and parietal cortex by means of structural magnetic resonance imaging and the default mode network by means of functional magnetic resonance imaging at rest as a biomarker of response to treatment and 5) associate the response to treatment with changes in Motor Evoked Potential (MEP) amplitude and latency in order to generate a response-to-treatment biomarker with neuromodulators in Mild Cognitive Impairment (MCI) and changes in electroencephalogram.

Conditions

• Mild Cognitive Impairment

Interventions

DEVICE

1. rTMS + CS

In the first phase each participant will receive 15 sessions of rTMS and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of rTMS and 1 session of CS per week for 12 weeks. Each session will consist of 10 trains of 10 stimuli, at a 5-Hz frequency and a stimulation intensity of 120% of the resting motor threshold. rTMS will be administered by a MagPro R30 stimulator (MagVenture) and an active/placebo 8-shape coil model MCF-B70. Two surface electrodes will be employed to replicate rTMS skin sensations near the stimulation site. The rTMS condition will be double-blinded through the use of a USB stick. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of rTMS and 21 sessions of CS.

DEVICE

2. rTMS Sham + CS

In the first phase each participant will receive 15 sessions of rTMS Sham and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of Sham rTMS and 1 session of CS per week for 12 weeks. In total, each participant will receive 27 sessions of Sham rTMS and 21 sessions of CS. rTMS will be administered by a MagPro R30 stimulator (MagVenture) and an active/placebo 8-shape coil model MCF-B70. Two surface electrodes will be employed to replicate rTMS skin sensations near the stimulation site. The sham condition will be double-blinded through the use of a USB stick. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of rTMS and 21 sessions of CS.

DEVICE

3. tDCS + CS

In the first phase each participant will receive 15 sessions of tDCS and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of tDCS and 1 session of CS per week for 12 weeks. Each session will consist of the delivery of a weak direct current of 2mA for 30 minutes. tDCS will be administered by the Sooma tDCS stimulator. The tDCS condition will be double-blinded, and a third operator will program the stimulator. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of tCDS and 21 sessions of CS.

DEVICE

4. tDCS Sham + CS

In the first phase each participant will receive 15 sessions of tDCS Sham and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of Sham tDCS and 1 session of CS per week for 12 weeks. tDCS will be administered by the Sooma tDCS stimulator. The sham condition will be double-blinded, and a third operator will program the stimulator. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of Sham tDCS and 21 sessions of CS.

Sponsors & Collaborators

• Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente

  lead OTHER

Principal Investigators

• Ruth Alcalá Lozano, Dr. · Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

55 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-01

Primary Completion

2027-01-01

Completion

2027-06-15

Countries

• Mexico

Study Locations