Mild Cognitive ImpairmentNCT06278818
Effects of Telerehabilitation on Brain Network Connectivity
A study testing Cognitive Telerehabilitation in people with Mild Cognitive Impairment, run by University of Pavia at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Cognitive Telerehabilitation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteItaly
- Study dates
- 7 Dec 2023to 1 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Mondino Foundation
Pavia, 27100
Cristina Tassorelli, MD, 0382380419 ext. 0039, cristina.tassorelli@unipv.it
Silvia Paola P Caminiti, PhD, 0382380419 ext. 0039, silviapaola.caminiti@unipv.it
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Cognitive Telerehabilitation, Control Condition
- Keywords
- Non-pharmacological treatments, Cognitive training, Rehabilitation, Dementia, Connectivity, Neuroimaging
- Medical subject headings
- Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive TelerehabilitationBehavioural
Cognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions.
Control ConditionOther
This activity is commonly used as a control condition to test the effectiveness of innovative rehabilitative treatments.
| Study group | Role | What they receive |
|---|---|---|
| Network-based Cognitive Training (NBCT) | Experimental | The training will be delivered through a virtual platform for TR. Receives: Behavioral: Cognitive Telerehabilitation |
| Home-based Cognitive Rehabilitation (HomeCoRe) | Experimental | The training will be delivered through a touch-screen laptop in a home-based setting. Receives: Behavioral: Cognitive Telerehabilitation |
| Semantic Memory Rehabilitation Training (SMRT) | Experimental | The training will be delivered through TR with the assistance of an online therapist. Receives: Behavioral: Cognitive Telerehabilitation |
| Unstructured Home-based Cognitive Stimulation (Control) | Sham comparator | The Control stimulation will be delivered through TR with therapist assistance. Receives: Other: Control Condition |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Between-session before (Week 0) - after (Week 6 +/-2) SMRT TR
Secondary outcomes (1)
Changes in neuropsychological and caregiver burden measures after TR
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start7 Dec 2023
- Primary completion7 Jun 2024 (estimated)
- Study completion1 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pavia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Parma, University of Bologna, University of Rome Tor Vergata
- Responsible party
- Sponsor
- Investigators
- Cristina Tassorelli, MD, Principal investigator, University of Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06278818
- Sponsor's protocol ID
- MNESYS-PE0000006
- Status last verified
- Feb 2024
- First submitted
- 6 Feb 2024
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Publication of the study protocol.
Publications
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.
PubMed 35737533Rodella 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.
PubMed 34156651Quaglini 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.
PubMed 31438328Manca 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.
PubMed 33269758Litvan 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.
PubMed 22275317De 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.
PubMed 29578486De 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.
PubMed 26688237Bernini 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.
PubMed 33519704Bernini 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.
PubMed 35002919Bernini 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.
PubMed 37868592Bernini 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.
PubMed 32895890Bernini 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.
PubMed 36750612Bernini 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.
PubMed 31256092Albert 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.
PubMed 21514249Caminiti 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.
PubMed 38993694
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural and Clinical Correlates of Rehabilitation in Neurodegenerative Conditions
- ClinicalTrials.gov ID
- NCT06278818
- Acronym / sponsor ID
- MNESYS-PE0000006
- Conditions
- Mild Cognitive Impairment
- Keywords
- Non-pharmacological treatments, Cognitive training, Rehabilitation, Dementia, Connectivity, Neuroimaging
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- University of PaviaUniversity, hospital or other
- Collaborators
- University of Parma, University of Bologna, University of Rome Tor Vergata
- Study start
- 7 Dec 2023 (actual)
- Primary completion
- 7 Jun 2024 (estimated)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 26 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Network-based Cognitive Training (NBCT) | Experimental | Behavioral: Cognitive TelerehabilitationThe training will be delivered through a virtual platform for TR. |
| Home-based Cognitive Rehabilitation (HomeCoRe) | Experimental | Behavioral: Cognitive TelerehabilitationThe training will be delivered through a touch-screen laptop in a home-based setting. |
| Semantic Memory Rehabilitation Training (SMRT) | Experimental | Behavioral: Cognitive TelerehabilitationThe training will be delivered through TR with the assistance of an online therapist. |
| Unstructured Home-based Cognitive Stimulation (Control) | Sham comparator | Other: Control ConditionThe Control stimulation will be delivered through TR with therapist assistance. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive TelerehabilitationCognitive training specifically designed to promote cognitive functions in early stages of neurodegenerative conditions. | Behavioural | Home-based Cognitive Rehabilitation (HomeCoRe), Network-based Cognitive Training (NBCT), Semantic Memory Rehabilitation Training (SMRT) |
| Control ConditionThis activity is commonly used as a control condition to test the effectiveness of innovative rehabilitative treatments. | Other | Unstructured Home-based Cognitive Stimulation (Control) |
Primary outcome
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.
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.
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.
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.
1 secondary outcome
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Background: PubMed 35737533Wright 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.
- Background: PubMed 34156651Rodella 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.
- Background: PubMed 31438328Quaglini 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.
- Background: PubMed 33269758Manca 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.
- Background: PubMed 22275317Litvan 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.
- Background: PubMed 29578486De 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.
- Background: PubMed 26688237De 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.
- Background: PubMed 33519704Bernini 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.
- Background: PubMed 35002919Bernini 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.
- Background: PubMed 37868592Bernini 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.
- Background: PubMed 32895890Bernini 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.
- Background: PubMed 36750612Bernini 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.
- Individual participant dataSharing planned: Yes. Publication of the study protocol.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cristina Tassorelli, MD principal investigator
University of Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Telerehabilitation in people with Mild Cognitive Impairment, run by University of Pavia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cristina Tassorelli, MD (0382380419 ext. 0039, cristina.tassorelli@unipv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in resting-state brain networks functional connectivity after NBTC treatment (time frame: Between-session before (Week 0) - after (Week 4 +/-2) NBCT TR). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06278818, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.