TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment

NCT04490616 | Completed

• 1 other identifier: 2020-00434/CE 3594
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment

Keywords

ripetitive transcranial magnetic stimulation treatment; social cognition; theory of mind; empathy; social perception; social behavior

Outcome Measures

Primary Outcomes (10)

• Comparison of Deceptive Box Task score

  (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

  (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  Week 2

• Comparison of Empathy Quotient score

  (60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.

  Week 2

• Comparison of Ekman 60 test score

  (60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.

  Week 2

• Comparison of Frontal Behavioral Inventory score

  (24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.

  Week 2

• Comparison of Deceptive Box Task score

  (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  Week 4

• Comparison of Look-prediction/say-prediction test

  (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  Week 4

• Comparison of Empathy Quotient score

  (60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.

  Week 4

• Comparison of Ekman 60 test score

  (60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.

  Week 4

• Comparison of Frontal Behavioral Inventory score

  (24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.

  Week 4

Secondary Outcomes (8)

• Changes from baseline in Deceptive Box Task Test.

  Week 12

• Changes from baseline in Look/say Test

  Week 12

• Changes from baseline in Empathy Quotient scale

  Week 12

• Changes from baseline in Ekman 60 Test

  Week 12

• Changes from baseline in Frontal Behavioral Inventory

  Week 12

Study Arms (2)

RR-GR

EXPERIMENTAL

MCI patients with social cognition deficits will receive 4 weeks of rTMS stimulation

Other: rTMS treatment

SR-GR

OTHER

MCI patients with social cognition deficits will receive 2 weeks of placebo treatment, followed by 2 weeks of real rTMS stimulation

Other: rTMS treatment

Interventions

rTMS treatment OTHER

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.

RR-GR; SR-GR

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ospedale Regionale di Lugano: lead

Study Sites (1)

Neurocentro della Svizzera italiana,Ospedale Regionale di Lugano

Lugano, Canton Ticino, 6903, Switzerland

Location

Related Publications (14)

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• Wondra JD, Ellsworth PC. An appraisal theory of empathy and other vicarious emotional experiences. Psychol Rev. 2015 Jul;122(3):411-28. doi: 10.1037/a0039252. Epub 2015 May 11.

  PMID: 25961468 BACKGROUND

• Apperly IA, Samson D, Chiavarino C, Humphreys GW. Frontal and temporo-parietal lobe contributions to theory of mind: neuropsychological evidence from a false-belief task with reduced language and executive demands. J Cogn Neurosci. 2004 Dec;16(10):1773-84. doi: 10.1162/0898929042947928.

  PMID: 15701227 BACKGROUND

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  PMID: 15563720 BACKGROUND

• Van Overwalle F. Social cognition and the brain: a meta-analysis. Hum Brain Mapp. 2009 Mar;30(3):829-58. doi: 10.1002/hbm.20547.

  PMID: 18381770 BACKGROUND

• Amodio DM, Frith CD. Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci. 2006 Apr;7(4):268-77. doi: 10.1038/nrn1884.

  PMID: 16552413 BACKGROUND

• Cabeza R, Ciaramelli E, Moscovitch M. Cognitive contributions of the ventral parietal cortex: an integrative theoretical account. Trends Cogn Sci. 2012 Jun;16(6):338-52. doi: 10.1016/j.tics.2012.04.008. Epub 2012 May 19.

  PMID: 22609315 BACKGROUND

• Dodich A, Cerami C, Crespi C, Canessa N, Lettieri G, Iannaccone S, Marcone A, Cappa SF, Cacioppo JT. Differential Impairment of Cognitive and Affective Mentalizing Abilities in Neurodegenerative Dementias: Evidence from Behavioral Variant of Frontotemporal Dementia, Alzheimer's Disease, and Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(4):1011-22. doi: 10.3233/JAD-150605.

  PMID: 26836153 BACKGROUND

• Freedman M, Binns MA, Black SE, Murphy C, Stuss DT. Theory of mind and recognition of facial emotion in dementia: challenge to current concepts. Alzheimer Dis Assoc Disord. 2013 Jan-Mar;27(1):56-61. doi: 10.1097/WAD.0b013e31824ea5db.

  PMID: 22407224 BACKGROUND

• Padala PR, Padala KP, Lensing SY, Jackson AN, Hunter CR, Parkes CM, Dennis RA, Bopp MM, Caceda R, Mennemeier MS, Roberson PK, Sullivan DH. Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study. Psychiatry Res. 2018 Mar;261:312-318. doi: 10.1016/j.psychres.2017.12.063. Epub 2018 Jan 5.

  PMID: 29331848 BACKGROUND

• Ferrari C, Vecchi T, Todorov A, Cattaneo Z. Interfering with activity in the dorsomedial prefrontal cortex via TMS affects social impressions updating. Cogn Affect Behav Neurosci. 2016 Aug;16(4):626-34. doi: 10.3758/s13415-016-0419-2.

  PMID: 27012713 BACKGROUND

• Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C. Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol. 2008 Dec;15(12):1286-92. doi: 10.1111/j.1468-1331.2008.02202.x.

  PMID: 19049544 BACKGROUND

• Cotelli M, Calabria M, Zanetti O. Cognitive rehabilitation in Alzheimer's Disease. Aging Clin Exp Res. 2006 Apr;18(2):141-3. doi: 10.1007/BF03327429.

  PMID: 16702783 BACKGROUND

• Riccitelli GC, Beeching F, Lecchi A, Ongaro G, Pertoldi W, Kaelin-Lang A, Sacco L. Enhancing Social Cognition in Mild Cognitive Impairment with Non-Invasive Brain Stimulation: A Randomized Clinical Trial. Neurorehabil Neural Repair. 2025 Dec;39(12):972-982. doi: 10.1177/15459683251360731. Epub 2025 Aug 21.

  PMID: 40838395 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Social Behavior

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavior

Study Officials

• Leonardo Sacco, Dr

  +41 091 811 6921

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In the project will be applied a two-site repetitive transcranial magnetic stimulation (rTMS) stimulation. MCI patients that obtained a score ≤ 10 percentiles, at least one performance/domain of social cognition assessment will be considered impaired at social cognition abilities. In the same day of cognitive-behavioral assessment, patients will be randomly assigned to one of the two groups: 1\) RR-Gr received 4 weeks of rTMS stimulation of the RTPJ and MPFC; (2) SR-Gr received of the RTPJ and MPFC sham stimulation during the first 2 weeks followed by 2 weeks of real stimulation. Each week of rTMS treatment consisted of five sessions. This paradigm has proven to be effective for improve cognitive performances in AD patients. In the sham condition, a sham coil will be used.

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 29, 2020
• Study Start: February 11, 2021
• Primary Completion: February 28, 2024
• Study Completion: March 31, 2024
• Last Updated: March 20, 2025

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)