TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment

March 17, 2025 updated by: Leonardo Sacco, Ospedale Regionale di Lugano

EFFECTS of RTMS TREATMENT on SOCIAL COGNITION DYSFUNCTIONS in MILD COGNITIVE IMPAIRMENT: an PROSPECTIVE, DOUBLE-BINDING, RANDOMIZED, SINGLE CENTRE, EXPLORATIVE STUDY

Social cognitive abilities are impaired in around 17% of subjects with mild cognitive impairment (MCI), and might not reflect upon functional status. Compared to healthy controls, MCI showed impairments in theory of mind (ToM) and facial emotion recognition. Moreover, in amnesic MCI patients, reduced ToM ability appears to be correlated with worse performances at several cognitive performances. These findings, in agreement with previous evidence, confirm that impaired social cognition might occur prior to dementia: typically elderly start to show impairment in the complex ToM levels, which is found also in MCI patients and proceeds further in AD patients. Thus, the treatment of these aspects has the potential to influence the trajectory of neurodegeneration. In the last decade, it has been increasingly evident the effectiveness of active stimulation of brain regions with repetitive transcranial magnetic stimulation (rTMS), to improve cognitive and functional performances in patients with dementia.

On the other hand, brain imaging techniques and TMS stimulations have identified two main areas responsible for human social cognition- the medial prefrontal cortex (MPFC) and the right temporo-parietal junction (RTPJ).

In this project, we hypothesized that an improvement of social cognition skills may be obtained in MCI patients by using the rTMS on two main areas responsible for human social cognition- the medial prefrontal cortex (MPFC) and the right temporoparietal junction (RTPJ). Moreover, it expects that rTMS treatment may also contribute to improving cognitive abilities and neuropsychiatric aspects partially modulated by the same networks stimulated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, double-binding, cross-sectional, randomized, sham-controlled, and single-center project aimed to investigate the effect of rTMS treatment of social cognition abilities in MCI subjects at 2 and 4 weeks, and after 8 weeks from baseline.

All patients will be recruited at Clinical Neuroscience Institute, Department of Neurology, Regional Civic Hospital, Lugan; Department of Geriatric Italian Hospital Viganello; and Department of Geriatric, Beata Vergine Hospital Mendrisio; Southern Switzerland, Switzerland.

Primary objective:

1. To investigate whether the application of high-frequency rTMS, for 2 or 4 weeks, to the RPTJ and MPFC resulted in social cognitive improvements.

Secondary objectives:

  1. To verify whether the social cognition benefits previously recorded might persist after 8 weeks the end of the stimulation, with a major benefit with a longer rTMS application (4 weeks).
  2. To investigate whether the application of high-frequency rTMS, at 2 weeks or 4 weeks, to the RPTJ and MPFC contributes to improve cognitive functions as well as neuropsychiatric (depression) and functional aspects.
  3. To verify whether the cognitive functions, neuropsychiatric aspect, and functional benefits previously recorded persist after the end of the rTMS stimulation.

Primary analysis: To investigate the behavioral effects induced by the rTMS protocol after 2 and 4 weeks of daily stimulation on social cognition skills, executive/attentive functions, neuropsychiatric and functional aspects will be used a mixed-model ANOVA, considering the group as a between-subjects factor, and time as a within-subject factor.

Secondary Analyses: To investigate the direct or mediated rTMS effect on social cognition skills, a multivariate linear regression analysis will be done for each social cognition measure (ToM, empathy, social perception, social behavior) changes after rTMS treatment at 2 and 4 weeks as the dependent factor, separately, and appropriate screening/baseline dependent variables and rTMS groups as independent factors.

The evaluation and treatment of social cognition alterations in subjects with MCI can be useful for two main aspects: first, the mild cognitive and behavior impairment of these subjects favor a better answer at the treatment, both at the behavioral level and in terms of brain structural and functional response; second, treatment of these abilities in MCI population might retard the conversion to dementia. More importantly, the detection of predominant social cognition alteration in early phases of cognitive decline might be potentially helpful to differentiate individuals who will develop frontotemporal dementia. Therefore, it is important to investigate and define a treatment protocol to limit social cognition disturbances in MCI.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • Ticino
      • Lugano, Ticino, Switzerland, 6903
        • Neurocentro della Svizzera italiana,Ospedale Regionale di Lugano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects aged 50 to 85 years old, inclusive, at the time of informed consent;
  • Must have at least 5 years of education or work experience to exclude mental deficits other than MCI;
  • Must meet Petersen's criteria for mild cognitive impairment, and must have:
  • Clinical dementia rating global score of 0.5;
  • Mini-Mental State Examination score between 24 and 30;
  • Must have a score ≥ 26.5 at Token test to ensure that subjects have the ability to understand the instructions and procedures;
  • Must have a score < 29 at Beck Depression Inventory to exclude major depression that could compromise the patient's ability to engage in the study;
  • Apart from a clinical diagnosis of MCI, the subject must be in good health;
  • Must be on stable dose of antidepressant (if applicable) for at least 2 months prior to the enrolment.

Exclusion Criteria:

  • Any uncontrolled medical or neurological/neurodegenerative condition (other than MCI);
  • Clinical significant unstable psychiatric illness requiring treatment with neuroleptic;
  • Transient ischemic attack, stroke, or any unexplained loss of consciousness or severe ongoing stressor within 1 year prior to screening;
  • History of seizure within10 years prior to screening;
  • Recent history of alcohol or substance abuse or use of cannabinoids;
  • Any other medical conditions that are not stable or controlled, or could affect the subject's safety or interfere with the study assessments and treatment;
  • Contraindication to having TMS treatment;
  • Inability to understand the purpose of the study or to comply with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RR-GR
MCI patients with social cognition deficits will receive 4 weeks of rTMS stimulation
Other: rTMS treatment

A two-site rTMS stimulation delivered by a Magstim unit featuring a double 70 mm cooled coil will be applied.

MCI patients will be randomly assigned to one of the two study groups:

  1. RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC);
  2. PL-Gr will receive sham stimulation of the RTPJ and MPFC during the first 2 weeks followed by 2 weeks of real stimulation. Each week of rTMS treatment will consist of five sessions (50 min, one per day).

For each area target, a total of 2000 pulses at 20Hz, 3-s train duration, and 28-s inter-train interval at 100% motor threshold (MT) will be delivered per session. A fixed intensity of MT will ensure a more consistent spatial spread of TMS effects in subjects' brains not influenced by differences in individual MT. In the sham condition, a sham coil will be used.

Each session lasted for about 60 min including time for set up and 50 min of stimulation.
Other: SR-GR
MCI patients with social cognition deficits will receive 2 weeks of placebo treatment, followed by 2 weeks of real rTMS stimulation
Other: rTMS treatment

A two-site rTMS stimulation delivered by a Magstim unit featuring a double 70 mm cooled coil will be applied.

MCI patients will be randomly assigned to one of the two study groups:

  1. RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC);
  2. PL-Gr will receive sham stimulation of the RTPJ and MPFC during the first 2 weeks followed by 2 weeks of real stimulation. Each week of rTMS treatment will consist of five sessions (50 min, one per day).

For each area target, a total of 2000 pulses at 20Hz, 3-s train duration, and 28-s inter-train interval at 100% motor threshold (MT) will be delivered per session. A fixed intensity of MT will ensure a more consistent spatial spread of TMS effects in subjects' brains not influenced by differences in individual MT. In the sham condition, a sham coil will be used.

Each session lasted for about 60 min including time for set up and 50 min of stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Deceptive Box Task score
Time Frame: Week 2
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 2
Comparison of Look-prediction/say-prediction test score
Time Frame: Week 2
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 2
Comparison of Empathy Quotient score
Time Frame: Week 2
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Week 2
Comparison of Ekman 60 test score
Time Frame: Week 2
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Week 2
Comparison of Frontal Behavioral Inventory score
Time Frame: Week 2
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Week 2
Comparison of Deceptive Box Task score
Time Frame: Week 4
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 4
Comparison of Look-prediction/say-prediction test
Time Frame: Week 4
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 4
Comparison of Empathy Quotient score
Time Frame: Week 4
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Week 4
Comparison of Ekman 60 test score
Time Frame: Week 4
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Week 4
Comparison of Frontal Behavioral Inventory score
Time Frame: Week 4
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from baseline in Deceptive Box Task Test.
Time Frame: Week 12
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 12
Changes from baseline in Look/say Test
Time Frame: Week 12
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Week 12
Changes from baseline in Empathy Quotient scale
Time Frame: Week 12
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Week 12
Changes from baseline in Ekman 60 Test
Time Frame: Week 12
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Week 12
Changes from baseline in Frontal Behavioral Inventory
Time Frame: Week 12
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Week 12
Comparison Montreal Cognitive Assessment
Time Frame: through study completion, an average of 12 weeks
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
through study completion, an average of 12 weeks
Comparison of Geriatric Depression Scale score
Time Frame: through study completion, an average of 12 weeks
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
through study completion, an average of 12 weeks
Comparison of Euroquol-5 dimensions score
Time Frame: athrough study completion, an average of 12 weeks
(visual analogue scale with 100-point scale). Minimum value=0, maximum value=100. Higher score means a better outcome.
athrough study completion, an average of 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ospedale Regionale di Lugano

Investigators

  • Principal Investigator: Leonardo Sacco, Dr, +41 091 811 6921

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2021

Primary Completion (Actual)

February 28, 2024

Study Completion (Actual)

March 31, 2024

Study Registration Dates

First Submitted

July 10, 2020

First Submitted That Met QC Criteria

July 24, 2020

First Posted (Actual)

July 29, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 17, 2025

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-00434/CE 3594

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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