Abstract
Background: Early or preclinical stages of AD continuum may benefit from lifestyle interventions and cognitive rehabilitation strategies that can delay or prevent progression to dementia. In this context, digital health technologies offer a disruptive potential to expand access to cognitive rehabilitation and meet the increasing demand for early interventions. This study protocol outlines a randomized controlled trial (RCT) designed to evaluate the efficacy and efficiency of a personalized, multidomain digital cognitive rehabilitation approach compared to conventional paper-and-pencil therapy. A secondary objective is to investigate the structural and functional neuroplasticity mechanisms associated with both interventions, using advanced magnetic resonance imaging techniques. Methods: The study presents a single-blinded (assessors) 1:1 parallel-arm RCT design involving 102 patients with Subjective Cognitive Decline, o Mild Cognitive Impairment or early-stage dementia. For the experimental intervention group (EG) the digital therapeutic RICORDO-DTx will be employed, while the control group (CG) will perform an unstructured pencil-paper stimulation program. Both interventions will last 5 weeks with 3 session/week. Outcome measures will evaluate efficacy as changes in: behavioural and cognitive abilities, patients’ engagement, and structural and functional neuroplasticity mechanisms by means of Magnetic Resonance Imaging. Additional evaluation will include efficiency measures related to usability, acceptability, safety, sustainability and user experience. Patients will be evaluated at baseline (T0), after treatment (T1) and at follow up six months post baseline (T2). Data analyses will involve repeated measures ANOVA models on primary and secondary outcome measures to compare efficacy of intervention between EG and CG. Finally, efficiency measures will be reported with descriptive statistics. Conclusions: The expected results lay on the ability of RICORDO DTx, to adapt task difficulty automatically based on patients’ performance and perceived difficulty. This adaptive approach is anticipated to yield superior treatment outcomes relative to traditional pencil-and-paper exercises. Trial registration: ClinicalTrials.gov NCT07064226.