Design and Validation of Innovative Strategies Based on Dual-Task Approach

Summary Description Neurological diseases such as Stroke Outcomes (SO), Multiple Sclerosis (MS), and Parkinson's disease (PD) cause complex and severe disabilities involving motor, cognitive, and autonomic domains. Widespread neuroinflammation contributes to progressive tissue damage in all three conditions. SARS-CoV-2 infection can further exacerbate neurological deficits through inflammatory mechanisms, and its long-term effects may aggravate pre-existing motor and cognitive impairments. Pharmacological therapies for these diseases-and for post-COVID neurological sequelae-offer limited benefit; therefore, neurorehabilitation represents a crucial therapeutic resource. Dual-task approaches, which simultaneously target cognitive and motor functions, have gained increasing interest because they better reflect daily life demands, align with embodied cognition theories, and allow concurrent intervention on multiple deficit domains. However, their efficacy has not been adequately assessed in SO, MS, and PD, and has not been investigated at all in individuals with long-term neurological consequences of SARS-CoV-2. This project aims to design and validate dual-task rehabilitation strategies in these populations and compare their outcomes with those of conventional rehabilitation. Background and State of the Art Individuals with SO, MS, and PD share multifaceted disabilities and underlying neuroinflammatory processes. The additional impact of COVID-19, especially in cases with persistent neurological manifestations, emphasizes the urgency of effective rehabilitation methods. Preliminary work by the research team includes studies on dual-task mechanisms and implementation in clinical settings, confirming feasibility and theoretical relevance. Nonetheless, rigorous randomized, controlled-possibly double-blind-trials are required to determine clinical efficacy. Project Activities and Organization The project includes the following integrated activities: Design and validation of dual-task rehabilitation strategies, encompassing: * dual motor tasks * dual cognitive tasks * combined motor-cognitive tasks Virtual and/or augmented reality environments will be used when beneficial. Pilot feasibility study in small groups (5 per diagnostic category: SO, MS, PD, long-term post-COVID) to assess applicability, patient acceptance, and preliminary efficacy. Conducted by OU1. Participant selection for the clinical trial (SO, MS, PD, with or without past SARS-CoV-2 infection) based on predefined inclusion/exclusion criteria. Conducted jointly by all OUs. Randomized controlled trial, conducted by OU1, OU3, and OU4, including: 1. Baseline motor, cognitive, and mood assessment using validated tools. 2. Implementation of dual-task strategies alongside standard rehabilitation, using emerging technological devices. 3. Re-assessment at treatment completion and at 3-month follow-up. Data integration in a unified database (OU1). Statistical analyses and interpretation, including advanced methods such as artificial neural networks (OU1). Dissemination through conferences and publications. Specific Aims Aim 1 - Development and feasibility testing of dual-task strategies Dual-task interventions will be designed by OU1 based on the three task combinations. A preliminary feasibility phase will enroll 20 participants (5 SO, 5 MS, 5 PD, 5 post-COVID). Strategies demonstrating the best balance of efficacy and acceptability will be selected for the clinical trial. Aim 2 - Application of validated strategies in a randomized controlled trial A total of 48 participants (16 SO, 16 MS, 16 PD) will be recruited; for each condition, half will have a history of SARS-CoV-2 infection with neurological symptoms persisting ≥4 weeks. Additional inclusion/exclusion criteria ensure safety and feasibility. Participants will be randomized into: * Experimental group: standard rehabilitation (3/week) with dual-task training (2/week, 30 min/session) * Control group: standard rehabilitation with placebo low-resistance cycling (2/week, 30 min/session) Aim 3 - Comparison of dual-task vs conventional rehabilitation outcomes Outcome measures will be compared between: * participants receiving standard with placebo therapy, and * participants receiving standard with dual-task therapy. Additionally, pre- and post-intervention blood samples will be analyzed for biomarkers of neuroinflammation and neurodegeneration, providing complementary insight into physiological changes associated with both rehabilitation modalities. Appropriate statistical methods, including machine-learning-based analyses, will be used to evaluate between-group and within-group differences.