AlzheimerVRTADNCT07722169
Telerehabilitation in Alzheimer's Disease
A study testing Online cognitive telerehabilitation and VRRS tablet in people with Alzheimer, run by IRCCS San Raffaele.
Trial summary
Telemedicine has developed rapidly during the COVID-19 pandemic and is now integrated into the clinical practice of many hospitals. Telemedicine offers many advantages, and even after the end of the pandemic, many patients still choose to undergo healthcare visits remotely. Read more about this study
- Who is it for?
- Ages 50 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer
- What is being tested?
- Online cognitive telerehabilitation and VRRS tablet
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Availability to assist the patient throughout the study.
- Ability and willingness to provide written informed consent.
- Exclusion criteria for patients with Alzheimer's disease (AD):
- Refusal or inability to provide written informed consent.
- History of psychiatric disorders.
Show all 14Show fewer
- Significant cerebrovascular disease.
- Severe visual or hearing impairment that could interfere with study procedures.
- Psychosis.
- Major depressive disorder.
- Alcohol or substance abuse.
- Use of psychotropic medications that may interfere with neuropsychological assessment or study treatment.
- Concurrent participation in another interventional pharmacological clinical trial.
- Any contraindication to undergoing EEG recording.
Who cannot join
- Refusal or inability to provide written informed consent.
- History of psychiatric disorders.
- Major depressive disorder.
- Alcohol or substance abuse.
- Use of psychotropic medications that may interfere with neuropsychological assessment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Home-based Virtual Reality Cognitive Training as an add-on to Telerehabilitation in Alzheimer's Disease: Validation of a Protocol to Slow Down Cognitive Decline and Reduce Caregivers' Burden
Telemedicine has developed rapidly during the COVID-19 pandemic and is now integrated into the clinical practice of many hospitals. Telemedicine offers many advantages, and even after the end of the pandemic, many patients still choose to undergo healthcare visits remotely. However, the rapid expansion of telemedicine may be associated with the risk of providing patients with unvalidated and uncontrolled telehealth solutions, potentially negatively impacting their health.
In this study, the researchers aim to investigate the effectiveness of remote cognitive training in patients with mild-to-moderate Alzheimer's disease (AD) using tablets equipped with virtual reality-based cognitive exercises. The investigators also aim to evaluate the impact of online supervision of cognitive training by a neuropsychologist and to compare the costs and burden of home-based versus hospital-based cognitive training in patients with AD. This project will define the optimal modalities for cognitive telerehabilitation to ensure validated protocols for the continuity of care in AD.
Read the detailed description
This project aims to use new technologies and telemedicine to ensure continuity of care and slow cognitive decline in patients with Alzheimer's disease (AD). The investigators also aim to reduce caregiver burden and healthcare costs for the national healthcare system.
The investigators hypothesize that patients provided with a VRRS tablet and undergoing autonomous cognitive training as an adjunct to cognitive telerehabilitation will achieve better cognitive outcomes than patients who do not receive a VRRS tablet.
The investigators also hypothesize that patients receiving both forms of cognitive training-autonomous training using the VRRS tablet combined with online cognitive telerehabilitation supervised by a professional neuropsychologist-will show greater improvements in cognitive function than patients who do not receive online cognitive telerehabilitation.
This is a prospective, interventional, randomized, single-blind, monocentric clinical study.
Study population: 48 patients with AD (MMSE score 18-24) and one caregiver for each patient (48 caregivers in total).
To minimize potential bias, the neuropsychologist responsible for patient and caregiver assessments will be blinded to treatment allocation.
Patients will be randomized in a 1:1:1 ratio to one of the following treatment groups:
- Intervention Group 1:** 16 patients provided with a VRRS tablet to perform autonomous home-based cognitive training (5 days per week), in addition to online cognitive telerehabilitation sessions supervised by a neuropsychologist at San Raffaele Hospital twice weekly.
- Intervention Group 2:** 16 patients provided with a VRRS tablet to perform autonomous home-based cognitive training (5 days per week), without neuropsychologist-supervised cognitive telerehabilitation.
- Comparator Group 3:** 16 patients receiving online cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly. These patients will not receive a VRRS tablet for home use.
No interim analysis is planned.
Study design:
Each group will undergo a 3-month intervention according to the following schedule.
Group 1:
Autonomous home-based cognitive training using the VRRS tablet for 1 hour per day, 5 days per week.
Remote cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly.
Group 2:
Autonomous home-based cognitive training using the VRRS tablet for 1 hour per day, 5 days per week.
No cognitive telerehabilitation sessions.
Group 3:
Remote cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly.
No VRRS tablet and no additional autonomous home-based cognitive training.
- Study visits:
Patients and caregivers will attend the following visits:
- Enrolment.
- Screening (Day 1) and treatment initiation.
- Post-treatment assessment (after 3 months of treatment).
- Follow-up assessment (3 months after completion of treatment).
- Methods of data collection
The following data will be collected:
- patients' neuropsychological performance;
- electroencephalographic (EEG) activity;
- caregivers' mental health and caregiver burden;
- system usability;
- costs associated with telerehabilitation and cognitive training.
- Assessment of patients' neuropsychological performance:
Patients will undergo a comprehensive neuropsychological assessment at three time points: baseline, after the 3-month treatment period, and at the 3-month follow-up.
The assessment battery will include:
- Montreal Cognitive Assessment (MoCA) (primary outcome): a screening tool for cognitive impairment providing a total score and six domain-specific index scores (Memory, Executive Function, Attention, Language, Visuospatial Ability, and Orientation). Total scores range from 0 to 30, with scores ≥26 generally considered normal.
- Mini-Mental State Examination (MMSE).
- Quality of Life in Alzheimer's Disease (QoL-AD).
- Geriatric Depression Scale (GDS).
- Attention Matrices.
- Raven's Progressive Matrices.
- Token Test.
- Semantic Fluency Test.
- Phonemic Fluency Test.
- Naming Test.
- Word-Picture Naming Test.
- Digit Span Test (forward and backward).
- Corsi Block-Tapping Test.
- Rey Complex Figure Test.
- Trail Making Test.
- EEG assessment:
Five minutes of resting-state EEG will be recorded using 32-channel EEG caps before and after the intervention to perform time-frequency analyses.
- Assessment of caregivers' mental health and burden:
- Beck Depression Inventory-II (BDI-II).
- Zarit Burden Interview.
Assessment of system usability:
System Usability Scale (SUS). Usability will be evaluated in terms of effectiveness, efficiency, and user satisfaction.
- Assessment of the costs of telerehabilitation and cognitive training:
The following cost components will be analysed:
- healthcare professional costs (neuropsychologist);
- outpatient clinic costs;
- telemedicine equipment costs for both patients and the hospital;
- patients' travel costs;
- cognitive training equipment costs;
- caregiver burden;
- system usability.
Any future research involving the collected data will require prior approval from the Ethics Committee (EC).
- Conditions
- Alzheimer
- Being tested
- Online cognitive telerehabilitation, VRRS tablet
- Keywords
- cognitive training, telerehabilitation, virtual reality, Alzheimer's disease, Cognitive functions, caregiver
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Online cognitive telerehabilitationDevice
Online sessions of cognitive telerehabilitation, twice a week, supervised by a neuropsychologist based at the San Raffaele hospital.
VRRS tabletDevice
Patients equipped with VRRS tablets to undergo autonomous home-based cognitive training (5 days a week).
| Study group | Role | What they receive |
|---|---|---|
| Tablet + Telerehabilitation | Experimental | Group 1: Participants will perform autonomous home-based cognitive training using a VRRS tablet (Khymeia Home Tablet) for 5 days per week, combined with online cognitive telerehabilitation sessions conducted twice weekly by a neuropsychologist based at San Raffaele Hospital (telemedicine sessions delivered remotely between the patient's home and the hospital). The intervention will last 3 months. Receives: Device: Online cognitive telerehabilitation; Device: VRRS tablet |
| Tablet only | Experimental | Group 2: Participants will perform autonomous home-based cognitive training using a VRRS tablet (Khymeia Home Tablet) for 5 days per week. No cognitive telerehabilitation sessions supervised by a neuropsychologist will be provided. The intervention will last 3 months. Receives: Device: VRRS tablet |
| Telerehabilitation only | Active comparator | Group 3: Participants will receive online cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly (telemedicine sessions delivered remotely between the patient's home and the hospital). Participants will not receive a VRRS tablet and will not perform additional autonomous home-based cognitive training. Receives: Device: Online cognitive telerehabilitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montreal Cognitive Assessment (MoCA)
MoCA is a screening instrument to detect cognitive impairment. It generates a total score and six domain-specific index scores: (1) Memory, (2) Executive Functioning, (3) Attention, (4) Language, (5) Visuospatial, and (6) Orientation. The total possible score is 30 points; a score of 26 or above is considered normal, while scores below 26 may indicate cognitive impairment. Increase in MoCA scores meaning improvement in cognitive functioning.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Secondary outcomes (16)
Electroencephalographic (EEG) activity
Patients' electroencephalographic activity: 5 min of resting state EEG will be recorded using a 32 channel cap in order to perform time-frequency analyses before and after training. EEG power in the alpha, beta and theta rangers will be analyzed.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Caregivers' mental status
- Beck Depression Inventory-II (BDI): 21-item self-report instrument assessing the common cognitive symptoms of depression. BDI is considered a valid and reliable instrument for depression screening in the general population. The BDI is scored by summing the highest ratings for each of the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3, and the total scores can range from 0 to 63. BDI total scores ranging from 0 to 13 represent "Minimal" depression; total scores from 14 to 19 represent "Mild" depression; total scores from 20 to 28 represent "Moderate" depression; and total scores from 29 to 63 represent "Severe" depression.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Caregivers' burden
Zarit Burden Interview: a standardized, 22-item assessment tool used by healthcare professionals to measure the subjective burden experienced by caregivers of individuals with chronic illnesses or dementia. It evaluates the emotional, physical, social, and financial impacts of caregiving to identify individuals at risk for burnout. It contains 22 questions rated on a 5-point scale (0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Quite frequently, 4 = Nearly always). The total score ranges from 0 to 88, with higher scores indicating greater perceived strain.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
System usability
System Usability Scale (SUS): a reliable, 10-item questionnaire used in research to quickly measure the perceived usability of a product, software, or website. Usability measurements consider different aspects: effectiveness (users can successfully achieve their goals), efficiency (how much effort and resources are spent to achieve those goals) and satisfaction (the experience was satisfactory). Participants rate 10 statements (alternating positive and negative) on a 5-point scale (1 = Strongly Disagree, 5 = Strongly Agree), covering areas like ease of use, consistency, and complexity. A SUS score does not represent a percentage. Instead, scores are generally understood using standardized benchmarks and grading scales: (1) 80.3: Excellent (Grade A); (2) 71 - 80: Good (Grade B); (3) 68: Okay/Average; (4) 51 - 68: Poor (Grade C/D); (5) <51: Worst Imaginable (Grade F).
Measured: At the end of the 3-month rehabilitation period.
Telerehabilitation's costs
The total costs for 3 months of telerehabilitation will be evaluated. Costs related to the following elements will be summed up:
- pay for a neuropsychologist twice a week, for 3 months;
- telemedicine equipment costs for patients (tablet, internet)
- telemedicine equipment costs for the hospital (computer, internet, room).
Measured: At 3 months follow-up.
Mini Mental State Examination (MMSE)
The MMSE is a 30-point, 11-question screening tool used by clinicians to assess cognitive impairment. It evaluates functions like memory, orientation, attention, language, and visuospatial skills, taking just 5 to 10 minutes to administer. It is most commonly used to detect conditions like dementia or track cognitive decline over time. The MMSE covers several key domains of mental ability to establish a comprehensive overview of a person's present cognitive performance: Orientation (10 points), registration (3 points), Attention and Calculation (5 points), Recall (3 points), Language and Visual Construction (9 points). Scores are tallied out of 30, with higher scores indicating better cognitive function. A score of 24 or higher is generally considered normal, while scores below that threshold suggest varying levels of cognitive impairment.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Quality of Live in Alzheimer's Disease (QoL-AD)
The QOL-AD is a 13-item questionnaire designed to assess-through both the patient and the caregiver-the quality of life (QOL) of patients diagnosed with Alzheimer's disease (AD). The scale comprises 13 items measuring physical condition, mood, memory, functional abilities, interpersonal relationships, the ability to participate in meaningful activities, financial situation, and global assessments of self and overall QOL. Items are rated on a four-point scale, with descriptors ranging from 1 (poor) to 4 (excellent). Separate scores are calculated for patients and caregivers and then combined into a composite score (QoL-AD CS), in which patient ratings are weighted twice as heavily as caregiver ratings.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Geriatric Depression Scale (GDS)
The most widely used rating scale for assessing depressive symptoms in frail elderly patients and patients with dementia. The scale consists of 15 binary-response questions (yes or no), each scored as 1 or 0. The final score ranges from 0 (no depressive symptoms) to 15 (probable presence of depression).
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Attention matrices
Attentional Matrices is a classic paper-and-pencil diagnostic tool primarily used to assess selective visual attention and visual scanning. It requires patients to rapidly identify and cross out target numbers hidden among distractors within a strict time limit. The test typically consists of three separate matrices containing rows and columns of random digits. The patient is handed a sheet and given a brief timeframe (usually 45 seconds) to scan the matrix and cross out specific, pre-defined target numbers. The task becomes progressively complex across the three matrices.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Raven's Progressive Matrices (RPM)
RPM are a widely used, non-verbal psychometric assessment designed to measure fluid intelligence, abstract reasoning, and problem-solving skills. It evaluates an individual's ability to deduce relationships, identify patterns, and impose meaning on complex, abstract visual information. Test-takers are presented with a series of visual matrices-typically 3 × 3 geometric patterns-with one piece missing. The goal is to identify the underlying logical rule governing the pattern and select the correct missing piece from a set of multiple-choice options. The test is "progressive" because the visual puzzles begin simply and become increasingly difficult, demanding more complex cognitive operations to solve as the test goes on.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Token test
The Token Test is a standardized neuropsychological assessment used to evaluate receptive language disorders (auditory comprehension). It requires patients to follow increasingly complex spoken commands to manipulate small, colored plastic shapes (tokens). During the assessment, 20 physical tokens-featuring combinations of two shapes (circles and squares), two sizes (large and small), and five colors (red, blue, green, yellow, and white)-are placed in front of the patient. The test is typically divided into six sections of increasing difficulty: Simple commands: "Touch the red circle"; Complex/Two-part commands: "Touch the large green square and the small red circle"; Relational commands: "Touch the red circle with the blue sqaure". While the original test by A widely used short version consists of 36 commands. Points are awarded for correct manipulations. Lower or cutoff scores (e.g., 25 or below on the 36-item version) indicate varying levels of receptive language impairments.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Semantic and phonemic fluency
emantic and phonemic fluency are critical neuropsychological tests evaluating language and executive functions like working memory, mental flexibility, and strategy generation. Semantic fluency requires producing words within a specific category (e.g., animals), heavily relying on temporal lobe networks and semantic memory. Phonemic fluency requires generating words starting with a specific letter (e.g., F, A, S), taxing frontal lobe executive systems and phonological knowledge. The primary score is the sum of all valid, unique words generated within the 60-second limit.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Naming
Naming test evaluates an individual's ability to retrieve and articulate the names of visually presented objects or pictures. It is primarily used to diagnose anomia (word-finding difficulty) and localize language impairments caused by stroke, traumatic brain injury, or neurodegenerative diseases like Alzheimer's.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Word-picture naming test
It is a core neuropsychological evaluation that asks a patient to verbally identify common objects, animals, or actions shown in pictures. It is used to measure lexical retrieval (word finding), semantic memory, and speech fluency. The examiner presents a series of line drawings or photographs one by one. The patient is asked to state the name of the object as quickly and accurately as possible.
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Digit Span test
The Digit Span test is a core neuropsychological assessment of memory. It features two parts: Digits Forward, which measures passive short-term verbal memory and attention by requiring verbatim repetition, and Digits Backward, which assesses executive working memory by demanding mental manipulation and sequence reversal. Digits Forward: The examiner reads a random sequence of numbers aloud (e.g., "5-8-2-1") at a rate of one digit per second. The participant must repeat the sequence in the exact same order. Digits Backward: The examiner reads a sequence of numbers, and the participant must repeat the sequence in reverse order (e.g., if the examiner says "3-9-2", the correct response is "2-9-3").
Measured: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Hospital-based cognitive training costs
The total costs for 3 months of cognitive rehabilitation in the outpatient clinic of the San Raffaele Hospital (Milan, Italy) will be evaluated.
Costs related to the following elements will be summed up:
- pay for a neuropsychologist twice a week, for 3 months;
- cognitive training equipment costs for the hospital (computer, rehabilitation material, outpatient room).
- costs related to patients' travel to and from the hospital.
Measured: At 3 months follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AlzheimerStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sandro Iannaccone, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07722169
- Sponsor's protocol ID
- RF-2024-12380126 VRTAD
- Acronym
- VRTAD
- Status last verified
- Jul 2026
- First submitted
- 3 Jul 2026
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share IPD since this is a monocentric study, but all outcomes will be recorded and stored on a eCRF platform and will be be able to share data if requested by other researchers.
Publications
Gatica-Rojas V, Mendez-Rebolledo G. Virtual reality interface devices in the reorganization of neural networks in the brain of patients with neurological diseases. Neural Regen Res. 2014 Apr 15;9(8):888-96. doi: 10.4103/1673-5374.131612.
PubMed 25206907Yang JG, Thapa N, Park HJ, Bae S, Park KW, Park JH, Park H. Virtual Reality and Exercise Training Enhance Brain, Cognitive, and Physical Health in Older Adults with Mild Cognitive Impairment. Int J Environ Res Public Health. 2022 Oct 15;19(20):13300. doi: 10.3390/ijerph192013300.
PubMed 36293881Laver KE, George S, Thomas S, Deutsch JE, Crotty M. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2015 Feb 12;2015(2):CD008349. doi: 10.1002/14651858.CD008349.pub3.
PubMed 25927099Buschert V, Bokde AL, Hampel H. Cognitive intervention in Alzheimer disease. Nat Rev Neurol. 2010 Sep;6(9):508-17. doi: 10.1038/nrneurol.2010.113. Epub 2010 Aug 17.
PubMed 20717104Emedoli D, Houdayer E, Della Rosa PA, Zito A, Brugliera L, Cimino P, Padul JD, Tettamanti A, Iannaccone S, Alemanno F. Continuity of care for patients with dementia during COVID-19 pandemic: flexibility and integration between in-person and remote visits. Front Public Health. 2024 Jan 8;11:1301949. doi: 10.3389/fpubh.2023.1301949. eCollection 2023.
PubMed 38259745Emedoli D, Alemanno F, Houdayer E, Brugliera L, Iannaccone S, Tettamanti A. Mobile application tool for remote rehabilitation after discharge from coronavirus disease-19 rehabilitation unit. Healthc Technol Lett. 2022 Aug 8;9(4-5):70-76. doi: 10.1049/htl2.12033. eCollection 2022 Aug-Oct.
PubMed 36225346Elbaz S, Cinalioglu K, Sekhon K, Gruber J, Rigas C, Bodenstein K, Naghi K, Lavin P, Greenway KT, Vahia I, Rej S, Sekhon H. A Systematic Review of Telemedicine for Older Adults With Dementia During COVID-19: An Alternative to In-person Health Services? Front Neurol. 2021 Dec 14;12:761965. doi: 10.3389/fneur.2021.761965. eCollection 2021.
PubMed 34970210Grabher BJ. Effects of Alzheimer Disease on Patients and Their Family. J Nucl Med Technol. 2018 Dec;46(4):335-340. doi: 10.2967/jnmt.118.218057. Epub 2018 Aug 23.
PubMed 30139888Manenti R, Gobbi E, Baglio F, Macis A, Ferrari C, Pagnoni I, Rossetto F, Di Tella S, Alemanno F, Cimino V, Binetti G, Iannaccone S, Bramanti P, Cappa SF, Cotelli M. Effectiveness of an Innovative Cognitive Treatment and Telerehabilitation on Subjects With Mild Cognitive Impairment: A Multicenter, Randomized, Active-Controlled Study. Front Aging Neurosci. 2020 Nov 16;12:585988. doi: 10.3389/fnagi.2020.585988. eCollection 2020.
PubMed 33304267
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Home-based Virtual Reality Cognitive Training as an add-on to Telerehabilitation in Alzheimer's Disease: Validation of a Protocol to Slow Down Cognitive Decline and Reduce Caregivers' Burden
- ClinicalTrials.gov ID
- NCT07722169
- Acronym / sponsor ID
- VRTAD / RF-2024-12380126 VRTAD
- Conditions
- Alzheimer
- Keywords
- cognitive training, telerehabilitation, virtual reality, Alzheimer's disease, Cognitive functions, caregiver
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 23 Jul 2026 (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.
Telemedicine has developed rapidly during the COVID-19 pandemic and is now integrated into the clinical practice of many hospitals. Telemedicine offers many advantages, and even after the end of the pandemic, many patients still choose to undergo healthcare visits remotely. However, the rapid expansion of telemedicine may be associated with the risk of providing patients with unvalidated and uncontrolled telehealth solutions, potentially negatively impacting their health.
In this study, the researchers aim to investigate the effectiveness of remote cognitive training in patients with mild-to-moderate Alzheimer's disease (AD) using tablets equipped with virtual reality-based cognitive exercises. The investigators also aim to evaluate the impact of online supervision of cognitive training by a neuropsychologist and to compare the costs and burden of home-based versus hospital-based cognitive training in patients with AD. This project will define the optimal modalities for cognitive telerehabilitation to ensure validated protocols for the continuity of care in AD.
Detailed description
This project aims to use new technologies and telemedicine to ensure continuity of care and slow cognitive decline in patients with Alzheimer's disease (AD). The investigators also aim to reduce caregiver burden and healthcare costs for the national healthcare system.
The investigators hypothesize that patients provided with a VRRS tablet and undergoing autonomous cognitive training as an adjunct to cognitive telerehabilitation will achieve better cognitive outcomes than patients who do not receive a VRRS tablet.
The investigators also hypothesize that patients receiving both forms of cognitive training-autonomous training using the VRRS tablet combined with online cognitive telerehabilitation supervised by a professional neuropsychologist-will show greater improvements in cognitive function than patients who do not receive online cognitive telerehabilitation.
This is a prospective, interventional, randomized, single-blind, monocentric clinical study.
Study population: 48 patients with AD (MMSE score 18-24) and one caregiver for each patient (48 caregivers in total).
To minimize potential bias, the neuropsychologist responsible for patient and caregiver assessments will be blinded to treatment allocation.
Patients will be randomized in a 1:1:1 ratio to one of the following treatment groups:
- Intervention Group 1:** 16 patients provided with a VRRS tablet to perform autonomous home-based cognitive training (5 days per week), in addition to online cognitive telerehabilitation sessions supervised by a neuropsychologist at San Raffaele Hospital twice weekly.
- Intervention Group 2:** 16 patients provided with a VRRS tablet to perform autonomous home-based cognitive training (5 days per week), without neuropsychologist-supervised cognitive telerehabilitation.
- Comparator Group 3:** 16 patients receiving online cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly. These patients will not receive a VRRS tablet for home use.
No interim analysis is planned.
Study design:
Each group will undergo a 3-month intervention according to the following schedule.
Group 1:
Autonomous home-based cognitive training using the VRRS tablet for 1 hour per day, 5 days per week.
Remote cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly.
Group 2:
Autonomous home-based cognitive training using the VRRS tablet for 1 hour per day, 5 days per week.
No cognitive telerehabilitation sessions.
Group 3:
Remote cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly.
No VRRS tablet and no additional autonomous home-based cognitive training.
- Study visits:
Patients and caregivers will attend the following visits:
- Enrolment.
- Screening (Day 1) and treatment initiation.
- Post-treatment assessment (after 3 months of treatment).
- Follow-up assessment (3 months after completion of treatment).
- Methods of data collection
The following data will be collected:
- patients' neuropsychological performance;
- electroencephalographic (EEG) activity;
- caregivers' mental health and caregiver burden;
- system usability;
- costs associated with telerehabilitation and cognitive training.
- Assessment of patients' neuropsychological performance:
Patients will undergo a comprehensive neuropsychological assessment at three time points: baseline, after the 3-month treatment period, and at the 3-month follow-up.
The assessment battery will include:
- Montreal Cognitive Assessment (MoCA) (primary outcome): a screening tool for cognitive impairment providing a total score and six domain-specific index scores (Memory, Executive Function, Attention, Language, Visuospatial Ability, and Orientation). Total scores range from 0 to 30, with scores ≥26 generally considered normal.
- Mini-Mental State Examination (MMSE).
- Quality of Life in Alzheimer's Disease (QoL-AD).
- Geriatric Depression Scale (GDS).
- Attention Matrices.
- Raven's Progressive Matrices.
- Token Test.
- Semantic Fluency Test.
- Phonemic Fluency Test.
- Naming Test.
- Word-Picture Naming Test.
- Digit Span Test (forward and backward).
- Corsi Block-Tapping Test.
- Rey Complex Figure Test.
- Trail Making Test.
- EEG assessment:
Five minutes of resting-state EEG will be recorded using 32-channel EEG caps before and after the intervention to perform time-frequency analyses.
- Assessment of caregivers' mental health and burden:
- Beck Depression Inventory-II (BDI-II).
- Zarit Burden Interview.
Assessment of system usability:
System Usability Scale (SUS). Usability will be evaluated in terms of effectiveness, efficiency, and user satisfaction.
- Assessment of the costs of telerehabilitation and cognitive training:
The following cost components will be analysed:
- healthcare professional costs (neuropsychologist);
- outpatient clinic costs;
- telemedicine equipment costs for both patients and the hospital;
- patients' travel costs;
- cognitive training equipment costs;
- caregiver burden;
- system usability.
Any future research involving the collected data will require prior approval from the Ethics Committee (EC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tablet + Telerehabilitation | Experimental | Device: Online cognitive telerehabilitation, Device: VRRS tabletGroup 1: Participants will perform autonomous home-based cognitive training using a VRRS tablet (Khymeia Home Tablet) for 5 days per week, combined with online cognitive telerehabilitation sessions conducted twice weekly by a neuropsychologist based at San Raffaele Hospital (telemedicine sessions delivered remotely between the patient's home and the hospital). The intervention will last 3 months. |
| Tablet only | Experimental | Device: VRRS tabletGroup 2: Participants will perform autonomous home-based cognitive training using a VRRS tablet (Khymeia Home Tablet) for 5 days per week. No cognitive telerehabilitation sessions supervised by a neuropsychologist will be provided. The intervention will last 3 months. |
| Telerehabilitation only | Active comparator | Device: Online cognitive telerehabilitationGroup 3: Participants will receive online cognitive telerehabilitation sessions supervised by a neuropsychologist twice weekly (telemedicine sessions delivered remotely between the patient's home and the hospital). Participants will not receive a VRRS tablet and will not perform additional autonomous home-based cognitive training. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age ≥18 years.
- Availability to assist the patient throughout the study.
- Ability and willingness to provide written informed consent.
- Refusal or inability to provide written informed consent.
- History of psychiatric disorders.
Key exclusion criteria (5 listed)
- Refusal or inability to provide written informed consent.
- History of psychiatric disorders.
- Major depressive disorder.
- Alcohol or substance abuse.
- Use of psychotropic medications that may interfere with neuropsychological assessment.
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 |
|---|---|---|
| Online cognitive telerehabilitationOnline sessions of cognitive telerehabilitation, twice a week, supervised by a neuropsychologist based at the San Raffaele hospital. | Device | Tablet + Telerehabilitation, Telerehabilitation only |
| VRRS tabletPatients equipped with VRRS tablets to undergo autonomous home-based cognitive training (5 days a week). | Device | Tablet + Telerehabilitation, Tablet only |
Primary outcome
Montreal Cognitive Assessment (MoCA)
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
MoCA is a screening instrument to detect cognitive impairment. It generates a total score and six domain-specific index scores: (1) Memory, (2) Executive Functioning, (3) Attention, (4) Language, (5) Visuospatial, and (6) Orientation. The total possible score is 30 points; a score of 26 or above is considered normal, while scores below 26 may indicate cognitive impairment. Increase in MoCA scores meaning improvement in cognitive functioning.
16 secondary outcomes
Electroencephalographic (EEG) activity
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Caregivers' mental status
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Caregivers' burden
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
System usability
Time frame: At the end of the 3-month rehabilitation period.
Telerehabilitation's costs
Time frame: At 3 months follow-up.
Mini Mental State Examination (MMSE)
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Quality of Live in Alzheimer's Disease (QoL-AD)
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Geriatric Depression Scale (GDS)
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Attention matrices
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Raven's Progressive Matrices (RPM)
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Token test
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Semantic and phonemic fluency
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Naming
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Word-picture naming test
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Digit Span test
Time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.
Hospital-based cognitive training costs
Time frame: At 3 months follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Background: PubMed 25206907Gatica-Rojas V, Mendez-Rebolledo G. Virtual reality interface devices in the reorganization of neural networks in the brain of patients with neurological diseases. Neural Regen Res. 2014 Apr 15;9(8):888-96. doi: 10.4103/1673-5374.131612.
- Background: PubMed 36293881Yang JG, Thapa N, Park HJ, Bae S, Park KW, Park JH, Park H. Virtual Reality and Exercise Training Enhance Brain, Cognitive, and Physical Health in Older Adults with Mild Cognitive Impairment. Int J Environ Res Public Health. 2022 Oct 15;19(20):13300. doi: 10.3390/ijerph192013300.
- Background: PubMed 25927099Laver KE, George S, Thomas S, Deutsch JE, Crotty M. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2015 Feb 12;2015(2):CD008349. doi: 10.1002/14651858.CD008349.pub3.
- Background: PubMed 20717104Buschert V, Bokde AL, Hampel H. Cognitive intervention in Alzheimer disease. Nat Rev Neurol. 2010 Sep;6(9):508-17. doi: 10.1038/nrneurol.2010.113. Epub 2010 Aug 17.
- Background: PubMed 38259745Emedoli D, Houdayer E, Della Rosa PA, Zito A, Brugliera L, Cimino P, Padul JD, Tettamanti A, Iannaccone S, Alemanno F. Continuity of care for patients with dementia during COVID-19 pandemic: flexibility and integration between in-person and remote visits. Front Public Health. 2024 Jan 8;11:1301949. doi: 10.3389/fpubh.2023.1301949. eCollection 2023.
- Background: PubMed 36225346Emedoli D, Alemanno F, Houdayer E, Brugliera L, Iannaccone S, Tettamanti A. Mobile application tool for remote rehabilitation after discharge from coronavirus disease-19 rehabilitation unit. Healthc Technol Lett. 2022 Aug 8;9(4-5):70-76. doi: 10.1049/htl2.12033. eCollection 2022 Aug-Oct.
- Background: PubMed 34970210Elbaz S, Cinalioglu K, Sekhon K, Gruber J, Rigas C, Bodenstein K, Naghi K, Lavin P, Greenway KT, Vahia I, Rej S, Sekhon H. A Systematic Review of Telemedicine for Older Adults With Dementia During COVID-19: An Alternative to In-person Health Services? Front Neurol. 2021 Dec 14;12:761965. doi: 10.3389/fneur.2021.761965. eCollection 2021.
- Background: PubMed 30139888Grabher BJ. Effects of Alzheimer Disease on Patients and Their Family. J Nucl Med Technol. 2018 Dec;46(4):335-340. doi: 10.2967/jnmt.118.218057. Epub 2018 Aug 23.
- Background: PubMed 33304267Manenti R, Gobbi E, Baglio F, Macis A, Ferrari C, Pagnoni I, Rossetto F, Di Tella S, Alemanno F, Cimino V, Binetti G, Iannaccone S, Bramanti P, Cappa SF, Cotelli M. Effectiveness of an Innovative Cognitive Treatment and Telerehabilitation on Subjects With Mild Cognitive Impairment: A Multicenter, Randomized, Active-Controlled Study. Front Aging Neurosci. 2020 Nov 16;12:585988. doi: 10.3389/fnagi.2020.585988. eCollection 2020.
- Individual participant dataSharing planned: No. We do not plan to share IPD since this is a monocentric study, but all outcomes will be recorded and stored on a eCRF platform and will be be able to share data if requested by other researchers.
Related trials for Alzheimer
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
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.
Questions about this trial
What is this clinical trial studying?
A study testing Online cognitive telerehabilitation and VRRS tablet in people with Alzheimer, run by IRCCS San Raffaele.
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 14 inclusion and 5 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: opening soon, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elise Houdayer, PhD (+390226435739, houdayer.elise@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montreal Cognitive Assessment (MoCA) (time frame: (1) before telerehabilitation, (2) at the end of the 3-month rehabilitation period, and (3) 3 months following the end of treatment.). 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 NCT07722169, which also lists 9 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 3 Aug 2026.