Effects of Telerehabilitation on Brain Network Connectivity

NCT06278818 | Recruiting

• 1 other identifier: MNESYS-PE0000006
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

The current project aims at assessing the impact of various cognitive telerehabilitation approaches on patients with Mild Cognitive Impairment (MCI) associated with neurodegenerative diseases, namely Alzheimer's disease (AD) and Parkinson's disease (PD). The study focuses on non-pharmacological interventions to maintain patients' residual functionality, limit disease progression, and improve quality of life for both patients and their caregivers. This longitudinal and multicenter study applies innovative cognitive telerehabilitation (TR) methods and evaluates their impact on functional parameters obtained with high-density electroencephalogram (HD-EEG) and resting-state functional magnetic resonance imaging (rsFMRI). The goal is to identify neurophysiological correlates of the effects of three different cognitive TR in individuals with MCI due to neurodegenerative conditions. The study aims to:

• Identify correlations between improvement in cognitive performance and functional brain data.
• Use acquired knowledge to develop neurologically guided TR approaches for broader use. The research will include patients diagnosed with MCI associated with neurodegenerative diseases. Primary outcome measures include changes in resting-state brain connectivity assessed through HD-EEG and rsFMRI. Secondary outcomes involve the assessment of changes in neuropsychological measures, caregiver burden, immediately after rehabilitation and after longitudinal follow-up. The study is designed to last 30 months, with follow-up assessments at three time points. The primary outcomes will be evaluated using rsFMRI and HD-EEG instrumental acquisitions, the secondary outcomes will be evaluated using clinical assessments and neuropsychological tests.

Conditions

Mild Cognitive Impairment

Keywords

Non-pharmacological treatments; Cognitive training; Rehabilitation; Dementia; Connectivity; Neuroimaging

Outcome Measures

Primary Outcomes (4)

• Changes in resting-state brain networks functional connectivity after NBTC treatment

  Change in the resting-state functional connectivity from Baseline (T0) to the end of NBCT TR (T1 after 4 weeks) as measured by rs-fMRI. Connectivity measures will be extracted by means of Independent Component Analysis (ICA) and seed-based connectivity analysis approaches. This approach allowed for a detailed exploration of the functional connectivity networks associated with potential effects of NBTC treatment.

  Between-session before (Week 0) - after (Week 4 +/-2) NBCT TR

• Changes in resting-state EEG coherence after NBTC treatment

  Change in the resting-state coherence from Baseline (T0) to the end of NBCT TR (T1 after 4 weeks) as measured by HD-EEG. Connectivity measures will be extracted by means of seed-based connectivity analysis. This approach allowed for a detailed exploration of the HD-EEG connectivity networks associated with potential effects of NBTC treatment.

  Between-session before (Week 0) - after (Week 4 +/-2) NBCT TR

• Changes in resting-state EEG coherence after HomeCore treatment

  Change in the resting-state coherence from Baseline (T0) to the end of HomeCore TR (T1 after 6 weeks) as measured by HD-EEG. Connectivity measures will be extracted by means of seed-based connectivity analysis. This approach allowed for a detailed exploration of the HD-EEG connectivity networks associated with potential effects of HomeCore treatment.

  Between-session before (Week 0) - after (Week 6 +/-2) HomeCore TR

• Changes in resting-state brain networks functional connectivity after SMRT treatment

  Change in the resting-state functional connectivity from Baseline (T0) to the end of SMRT TR (T1 after 6 weeks) as measured by rs-fMRI. Connectivity measures will be extracted by means of Independent Component Analysis (ICA) and seed-based connectivity analysis approaches. This approach allowed for a detailed exploration of the functional connectivity networks associated with potential effects of SMRT treatment.

  Between-session before (Week 0) - after (Week 6 +/-2) SMRT TR

Secondary Outcomes (1)

• Changes in neuropsychological and caregiver burden measures after TR

  Between-session TO (Week 0) - T1 (Week 4 +/-2 or 6 +/-2) - T2 (Week 30+/-2 or 32+/-2) - T3 (Week 56+/-2 or 58+/-2)

Study Arms (4)

Network-based Cognitive Training (NBCT)

EXPERIMENTAL

The training will be delivered through a virtual platform for TR.

Behavioral: Cognitive Telerehabilitation

Home-based Cognitive Rehabilitation (HomeCoRe)

EXPERIMENTAL

The training will be delivered through a touch-screen laptop in a home-based setting.

Behavioral: Cognitive Telerehabilitation

Semantic Memory Rehabilitation Training (SMRT)

EXPERIMENTAL

The training will be delivered through TR with the assistance of an online therapist.

Behavioral: Cognitive Telerehabilitation

Unstructured Home-based Cognitive Stimulation (Control)

SHAM COMPARATOR

The Control stimulation will be delivered through TR with therapist assistance.

Other: Control Condition

Interventions

Cognitive Telerehabilitation BEHAVIORAL

Cognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions.

Home-based Cognitive Rehabilitation (HomeCoRe); Network-based Cognitive Training (NBCT); Semantic Memory Rehabilitation Training (SMRT)

Control Condition OTHER

This activity is commonly used as a control condition to test the effectiveness of innovative rehabilitative treatments.

Unstructured Home-based Cognitive Stimulation (Control)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed clinical diagnosis of MCI due to possible Alzheimer\'s disease with evidence of AD pathophysiological processes, according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria (Albert et al., 2011);
• Ability to understand and consciously sign informed consent and adhere to study procedures.
• Educational level ≥ 5 years.
• Clinical diagnosis of MCI-PD according to Level II criteria (Litvan et al., 2012). Ability to understand and consciously sign informed consent and adhere to study procedures.
• Educational level ≥ 5 years.

You may not qualify if:

• Aphasia, visuospatial neglect;
• Atypical and/or secondary parkinsonisms;
• Dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria;
• Alterations of consciousness;
• Sensory disorders that could interfere with the execution of tests and rehabilitative treatment;
• Concurrent psychiatric and/or neurological and/or essential tremor disorders;
• Presence of systemic inflammatory and infectious diseases, autoimmune diseases, malignant tumors at the time of recruitment, deemed clinically significant by the investigator and therefore capable of interfering with the study results;
• Inability or unwillingness to undergo MRI and/or EEG;
• Presence of prostheses or metallic implants incompatible with MRI;
• Deep brain stimulation (DBS) implant.
• Any dropouts will be managed by enrolling new patients.

Sponsors & Collaborators

• University of Pavia: lead
• University of Parma: collaborator
• University of Bologna: collaborator
• University of Rome Tor Vergata: collaborator

Study Sites (1)

IRCCS Mondino Foundation

Pavia, 27100, Italy

RECRUITING

Related Publications (15)

• Wright LM, De Marco M, Venneri A. Verbal fluency discrepancies as a marker of the prehippocampal stages of Alzheimer's disease. Neuropsychology. 2023 Oct;37(7):790-800. doi: 10.1037/neu0000836. Epub 2022 Jun 23.

  PMID: 35737533 BACKGROUND

• Rodella C, Bernini S, Panzarasa S, Sinforiani E, Picascia M, Quaglini S, Cavallini E, Vecchi T, Tassorelli C, Bottiroli S. A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment. Aging Clin Exp Res. 2022 Jan;34(1):73-83. doi: 10.1007/s40520-021-01912-0. Epub 2021 Jun 22.

  PMID: 34156651 BACKGROUND

• Quaglini S, Panzarasa S, Alloni A, Sacchi M, Sinforiani E, Bottiroli S, Bernini S. HomeCoRe: Bringing Cognitive Rehabilitation at Home. Stud Health Technol Inform. 2019 Aug 21;264:1755-1756. doi: 10.3233/SHTI190632.

  PMID: 31438328 BACKGROUND

• Manca R, Mitolo M, Wilkinson ID, Paling D, Sharrack B, Venneri A. A network-based cognitive training induces cognitive improvements and neuroplastic changes in patients with relapsing-remitting multiple sclerosis: an exploratory case-control study. Neural Regen Res. 2021 Jun;16(6):1111-1120. doi: 10.4103/1673-5374.300450.

  PMID: 33269758 BACKGROUND

• Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012 Mar;27(3):349-56. doi: 10.1002/mds.24893. Epub 2012 Jan 24.

  PMID: 22275317 BACKGROUND

• De Marco M, Venneri A. Volume and Connectivity of the Ventral Tegmental Area are Linked to Neurocognitive Signatures of Alzheimer's Disease in Humans. J Alzheimers Dis. 2018;63(1):167-180. doi: 10.3233/JAD-171018.

  PMID: 29578486 BACKGROUND

• De Marco M, Meneghello F, Duzzi D, Rigon J, Pilosio C, Venneri A. Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging. Brain Res Bull. 2016 Mar;121:26-41. doi: 10.1016/j.brainresbull.2015.12.001. Epub 2015 Dec 11.

  PMID: 26688237 BACKGROUND

• Bernini S, Stasolla F, Panzarasa S, Quaglini S, Sinforiani E, Sandrini G, Vecchi T, Tassorelli C, Bottiroli S. Cognitive Telerehabilitation for Older Adults With Neurodegenerative Diseases in the COVID-19 Era: A Perspective Study. Front Neurol. 2021 Jan 14;11:623933. doi: 10.3389/fneur.2020.623933. eCollection 2020.

  PMID: 33519704 BACKGROUND

• Bernini S, Panzarasa S, Sinforiani E, Quaglini S, Cappa SF, Cerami C, Tassorelli C, Vecchi T, Bottiroli S. HomeCoRe for Telerehabilitation in Mild or Major Neurocognitive Disorders: A Study Protocol for a Randomized Controlled Trial. Front Neurol. 2021 Dec 23;12:752830. doi: 10.3389/fneur.2021.752830. eCollection 2021.

  PMID: 35002919 BACKGROUND

• Bernini S, Ballante E, Fassio F, Panzarasa S, Quaglini S, Riccietti C, Costa A, Cappa SF, Tassorelli C, Vecchi T, Bottiroli S. In person versus remote cognitive rehabilitation in patients with subjective cognitive decline or neurocognitive disorders: what factors drive patient's preference? Front Psychol. 2023 Oct 4;14:1266314. doi: 10.3389/fpsyg.2023.1266314. eCollection 2023.

  PMID: 37868592 BACKGROUND

• Bernini S, Panzarasa S, Barbieri M, Sinforiani E, Quaglini S, Tassorelli C, Bottiroli S. A double-blind randomized controlled trial of the efficacy of cognitive training delivered using two different methods in mild cognitive impairment in Parkinson's disease: preliminary report of benefits associated with the use of a computerized tool. Aging Clin Exp Res. 2021 Jun;33(6):1567-1575. doi: 10.1007/s40520-020-01665-2. Epub 2020 Sep 8.

  PMID: 32895890 BACKGROUND

• Bernini S, Gerbasi A, Panzarasa S, Quaglini S, Ramusino MC, Costa A, Avenali M, Tassorelli C, Vecchi T, Bottiroli S. Outcomes of a computer-based cognitive training (CoRe) in early phases of cognitive decline: a data-driven cluster analysis. Sci Rep. 2023 Feb 7;13(1):2175. doi: 10.1038/s41598-022-26924-2.

  PMID: 36750612 BACKGROUND

• Bernini S, Alloni A, Panzarasa S, Picascia M, Quaglini S, Tassorelli C, Sinforiani E. A computer-based cognitive training in Mild Cognitive Impairment in Parkinson's Disease. NeuroRehabilitation. 2019;44(4):555-567. doi: 10.3233/NRE-192714.

  PMID: 31256092 BACKGROUND

• Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.

  PMID: 21514249 BACKGROUND

• Caminiti SP, Bernini S, Bottiroli S, Mitolo M, Manca R, Grillo V, Avenali M, De Icco R, Capellari S, Carlesimo GA, Venneri A, Tassorelli C. Exploring the neural and behavioral correlates of cognitive telerehabilitation in mild cognitive impairment with three distinct approaches. Front Aging Neurosci. 2024 Jun 27;16:1425784. doi: 10.3389/fnagi.2024.1425784. eCollection 2024.

  PMID: 38993694 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Cristina Tassorelli, MD

  University of Pavia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Tassorelli, MD

CONTACT

0382380419; cristina.tassorelli@unipv.it

Silvia P Caminiti, PhD

CONTACT

0382380419; silviapaola.caminiti@unipv.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The neurophysiologist and neuroradiologist will be blinded to the type of rehabilitation treatment (experimental group vs. control).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 26, 2024
• Study Start: December 7, 2023
• Primary Completion: June 7, 2024
• Study Completion: March 1, 2026
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be available after acceptance of the study protocol by the Open Access Journal.
• Access Criteria: Paper download.

Locations

IT (1)