Telerehabilitation in Alzheimer's Disease (VRTAD)

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:

1. Enrolment.
2. Screening (Day 1) and treatment initiation.
3. Post-treatment assessment (after 3 months of treatment).

4. 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).