Effects of Telerehabilitation on Brain Network Connectivity

February 19, 2024 updated by: University of Pavia

Neural and Clinical Correlates of Rehabilitation in Neurodegenerative Conditions

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, the impact of drug therapies on neurodegenerative conditions is very limited; The drugs available are mostly symptomatic and recent drug trials with new molecules have given contrasting results about the possibility of slowing down progression of disease. Therefore, clinically there is a strong interest in possible non-pharmacological intervention strategies for preserving functionality and limiting progression of disease as far as possible, reducing disability, and improving quality of life for both patients and their caregivers. Neurodegenerative diseases, such as Alzheimer's disease (AD) and, in some cases Parkinson's disease (PD), are characterized by a progressive cognitive decline. During the initial and mild cognitive impairment (MCI) phase, subjects report subjective disorders and show an objective and measurable cognitive impairment, although they maintain independence in day-to-day life activities. No consensus has been reached on the effect of non-pharmacological approaches to contrast cognitive decline, but there is a general agreement that these approaches are more likely to succeed the sooner they are implemented and the more accurately they act on the domains involved in the cognitive decline process.

The current longitudinal and multicenter study aims to apply innovative cognitive telerehabilitation (TR) approaches to the MCI population, to assess the impact of the different cognitive telerehabilitation approaches on brain network connectivity, acquired by means of high-density electroencephalogram (HD-EEG) and functional magnetic resonance imaging at rest (rs-fMRI). Moreover, the protocol will evaluate the effects of cognitive TR on neuropsychological measures. The primary outcome will be evaluated by means of a direct comparison between brain network connectivity measures before and after the intervention and by means of a comparison with a control group of MCI subjects, who will be involved in unstructured cognitive activities.

Condition Condition: Early stages of cognitive impairment due to neurodegenerative diseases, i.e. AD and PD.

Telerehabilitation Approaches Network-based Cognitive Training (NBCT) - A cognitive training specifically designed to promote the co-activation of multiple brain areas (i.e., central nodes), modulating the functional connectivity of specific resting state networks (RSNs) (i.e., Default Mode Network, DMN, e Salience Network, SN). This rehabilitation package has been used in face-to-face mode on a sample of healthy subjects (average age: 66 years), in whom a rehabilitation-induced "up-regulation" effect of the functional connectivity of the rear central nodes of the DMN was observed. Subsequently, this training approach has been tested in MCI-AD, MCI-PD and in patients with relapsing-remitting multiple sclerosis who complained of mild cognitive deficits. Within the framework of this study, the rehabilitation program will be implemented on a telerehabilitation platform (i.e. Khymeia) and will be administered through a virtual connection. A link will be provided for each rehabilitation session, which will allow participants to access and use the rehabilitation protocol through a web browser on their personal computer, tablet or mobile. This approach offers many advantages in terms of practicality, ease of use and accessibility for study participants.

Home-based Cognitive Rehabilitation (HomeCoRe) system - software for cognitive rehabilitation specially developed for the initial stages of deterioration (amnestic MCI, MCI-PD, mild AD), the usability and effectiveness of both in the person version (CoRe), as well as in remote rehabilitation (HomeCore) in the short and long term has been verified in the hospital field also in combination with neurostimulation techniques. HomeCoRe is an adaptive patient-tailored treatment that returns a Weighted score of performance for each exercise and each session to monitor patient's progress even remotely and adjust the level of difficulty of the proposed exercises accordingly. The mentioned strategy is applied to avoid over or under stimulation of the patient. The software provides an easy to access platform through which the patient interacts via a touch screen. The usability and acceptance of the home version of HomeCoRe has already been tested in a small group of patients in the early stages of cognitive impairment.

Semantic Memory Rehabilitation Training (SMRT) - Building upon the crucial role that the processing of semantic aspects of episodic information plays in long-term episodic memory processes, and recent evidence indicating early involvement of semantic memory in preclinical forms of Alzheimer's disease, the current cognitive training aims to enhance semantic processing in patients with MCI. The dual objective is to improve both episodic and semantic memory processes. A pilot study has yielded encouraging results in a small group of patients. The protocol is administered through telerehabilitation using a specific device with constant assistance from an online therapist.

Unstructured Home-based Cognitive Stimulation (Control) - This activity is commonly used as a control condition to test the effectiveness of innovative rehabilitative treatments, such as NBTC, HomeCoRe, and SMRT in this case. The treatment involves 60 minutes of daily activities (frequency and overall treatment duration will be adapted to the experimental treatment for comparison). Patients will receive instructions from the therapist along with a participant diary. For each session, few newspaper articles will be provided for the patient to read and summarize in the diary by answering specific questions. The protocol is administered through tele-rehabilitation using a specific device with constant assistance from an online therapist.

Study Type

Interventional

Enrollment (Estimated)

110

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 Contact

Study Contact Backup

Study Locations

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria for MCI-AD subjects:

  • 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.

Inclusion criteria for MCI-PD subjects:

  • 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.

Exclusion criteria:

  • 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.

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: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Network-based Cognitive Training (NBCT)
The training will be delivered through a virtual platform for TR.
Behavioral: Cognitive Telerehabilitation
Cognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions.
Experimental: Home-based Cognitive Rehabilitation (HomeCoRe)
The training will be delivered through a touch-screen laptop in a home-based setting.
Behavioral: Cognitive Telerehabilitation
Cognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions.
Experimental: Semantic Memory Rehabilitation Training (SMRT)
The training will be delivered through TR with the assistance of an online therapist.
Behavioral: Cognitive Telerehabilitation
Cognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions.
Sham Comparator: Unstructured Home-based Cognitive Stimulation (Control)
The Control stimulation will be delivered through TR with therapist assistance.
Other: Control Condition
This activity is commonly used as a control condition to test the effectiveness of innovative rehabilitative treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in resting-state brain networks functional connectivity after NBTC treatment
Time Frame: Between-session before (Week 0) - after (Week 4 +/-2) NBCT TR
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
Time Frame: Between-session before (Week 0) - after (Week 4 +/-2) NBCT TR
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
Time Frame: Between-session before (Week 0) - after (Week 6 +/-2) HomeCore TR
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
Time Frame: Between-session before (Week 0) - after (Week 6 +/-2) SMRT TR
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in neuropsychological and caregiver burden measures after TR
Time Frame: 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)
The efficacy of TR will be assessed by comparing neuropsychological tests and caregiver burden measures obtained across evaluation sessions (T0-T3). Changes in neuropsychological and caregiver burden measures will be correlated with the strength of changes in rs-fMRI or HD-EEG brain connectivity obtained comparing T0 to T1.
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)

Collaborators and Investigators

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

Sponsor

University of Pavia

Collaborators

University of Bologna
University of Rome Tor Vergata
University of Parma

Investigators

  • Principal Investigator: Cristina Tassorelli, MD, University of Pavia

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)

December 7, 2023

Primary Completion (Estimated)

June 7, 2024

Study Completion (Estimated)

March 1, 2026

Study Registration Dates

First Submitted

February 6, 2024

First Submitted That Met QC Criteria

February 19, 2024

First Posted (Estimated)

February 26, 2024

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MNESYS-PE0000006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Publication of the study protocol.

IPD Sharing Time Frame

The data will be available after acceptance of the study protocol by the Open Access Journal.

IPD Sharing Access Criteria

Paper download.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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