TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment

Mild Cognitive Impairment Clinical Trial

Official title:

EFFECTS OF rTMS TREATMENT ON SOCIAL COGNITION DYSFUNCTIONS IN MILD COGNITIVE IMPAIRMENT: AN PROSPECTIVE, DOUBLE-BINDING, RANDOMIZED, SINGLE CENTRE, EXPLORATIVE STUDY

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04490616
• Other study ID #: 2020-00434/CE 3594
• Status: Recruiting
• Phase: N/A
• Start date: February 11, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: September 2022
• Source: Ospedale Regionale di Lugano
• Contact: Leonardo Sacco, Dr
• Phone: +41 091 811 6921
• Email: leonardo.sacco[@]eoc.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: August 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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: RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC); 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.

Locations

Country	Name	City	State
Switzerland	Neurocentro della Svizzera italiana,Ospedale Regionale di Lugano	Lugano	Ticino

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale Regionale di Lugano

Country where clinical trial is conducted

Switzerland, 

References & Publications (13)

Adolphs R. The social brain: neural basis of social knowledge. Annu Rev Psychol. 2009;60:693-716. doi: 10.1146/annurev.psych.60.110707.163514. Review. — View Citation

Amodio DM, Frith CD. Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci. 2006 Apr;7(4):268-77. Review. — View Citation

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 — View Citation

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. Review. — View Citation

Cotelli M, Calabria M, Zanetti O. Cognitive rehabilitation in Alzheimer's Disease. Aging Clin Exp Res. 2006 Apr;18(2):141-3. Review. — View Citation

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. — View Citation

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 Frontotempora — View Citation

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. — View Citation

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. — View Citation

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, sh — View Citation

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. — View Citation

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. — View Citation

Wood JN, Knutson KM, Grafman J. Psychological structure and neural correlates of event knowledge. Cereb Cortex. 2005 Aug;15(8):1155-61. Epub 2004 Nov 24. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Deceptive Box Task score	(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.	Week 2
Primary	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
Primary	Comparison of Empathy Quotient score	(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.	Week 2
Primary	Comparison of Ekman 60 test score	(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.	Week 2
Primary	Comparison of Frontal Behavioral Inventory score	(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.	Week 2
Primary	Comparison of Deceptive Box Task score	(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.	Week 4
Primary	Comparison of Look-prediction/say-prediction test	(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.	Week 4
Primary	Comparison of Empathy Quotient score	(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.	Week 4
Primary	Comparison of Ekman 60 test score	(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.	Week 4
Primary	Comparison of Frontal Behavioral Inventory score	(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.	Week 4
Secondary	Changes from baseline in Deceptive Box Task Test.	(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.	Week 12
Secondary	Changes from baseline in Look/say Test	(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.	Week 12
Secondary	Changes from baseline in Empathy Quotient scale	(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.	Week 12
Secondary	Changes from baseline in Ekman 60 Test	(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.	Week 12
Secondary	Changes from baseline in Frontal Behavioral Inventory	(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.	Week 12
Secondary	Comparison Montreal Cognitive Assessment	(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.	through study completion, an average of 12 weeks
Secondary	Comparison of Geriatric Depression Scale score	(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.	through study completion, an average of 12 weeks
Secondary	Comparison of Euroquol-5 dimensions score	(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