Early Neuropsychological Rehabilitation and Family Psychoeducation After Ischemic Stroke

Background and rationaleCognitive deficits are frequent after ischemic stroke and may adversely affect functionalrecovery, quality of life, emotional well‐being, and participation in rehabilitation.Although recovery trajectories vary considerably between individuals, the earlypoststroke period represents an important phase of cognitive, functional, andpsychosocial adaptation. Evidence regarding structured cognitive rehabilitation initiatedduring this early period remains limited.Stroke also has important consequences for family members and informal caregivers.Caregivers may experience substantial burden associated with functional dependence,cognitive and behavioral changes, emotional difficulties, and the demands of providingongoing support. Structured psychoeducational interventions may help caregiversunderstand the consequences of stroke and develop appropriate strategies for supportingrecovery and adaptation.This trial evaluates both dimensions simultaneously by examining computerizedneuropsychological rehabilitation directed at the patient and structured familypsychoeducation directed at the primary family caregiver.ProceduresParticipants are recruited during the acute phase of ischemic stroke, within 96 hours ofsymptom onset. Baseline assessment of the primary outcome is performed approximately 20days after the index stroke, before randomization and before either intervention begins.Randomization is performed after completion of this baseline assessment.Allocation is stratified according to receipt of acute reperfusion therapy, defined asintravenous thrombolysis and/or mechanical thrombectomy versus no reperfusion treatment.Reperfusion status is used as a prespecified prognostic stratification factor.Randomization is implemented through the REDCap electronic data capture system usingrandomly permuted blocks of variable size. The allocation sequence is inaccessible topersonnel responsible for recruitment and eligibility assessment, and the next treatmentassignment cannot be anticipated.Both intervention factors begin after randomization, approximately 20 days after theindex stroke, and continue for approximately 12 weeks. The primary outcome assessment isscheduled at 3 months after stroke, corresponding to 90 days ±14 days. An optional12‐month follow‐up constitutes an observational extension and is not part of the primaryrandomized trial analysis.Participants allocated to computerized neuropsychological rehabilitation receive 24sessions of structured computerized cognitive training using the GuttmannNeuroPersonalTrainer platform. Sessions last 45 minutes and are delivered twice weeklyover approximately 12 weeks. The sequence and duration of the cognitive exercises arestandardized, while task difficulty is individually adjusted by the platform according toprevious performance. The intervention targets attention, processing speed, memory,executive functions, language, visuospatial abilities, and functional transfer of trainedstrategies.Participants not allocated to computerized neuropsychological rehabilitation receive anactive digital control condition consisting of simple recreational digital activitiesmatched in duration and frequency. These activities do not incorporate adaptivedifficulty, structured therapeutic progression, or cognitive performance feedback.Primary family caregivers allocated to structured family psychoeducation receive sixindividual 45‐minute sessions delivered by videoconference approximately every 2 weeksover 12 weeks. The program includes stroke education, the role of the family in recovery,emotional management, behavioral difficulties, cognitive restructuring, relaxation,self‐compassion, mindfulness‐based coping strategies, and behavioral activation.Caregivers are not trained in cognitive rehabilitation techniques in order to preservethe conceptual independence of the two factorial intervention components.Primary family caregivers not allocated to structured psychoeducation receive a briefinformational leaflet at the approximately 20‐day visit after randomization. The leafletprovides general information about stroke and its physical, communicative, cognitive,emotional, and behavioral consequences, together with recommended educational resources.It does not include behavioral management strategies, structured psychoeducationaltechniques, or cognitive rehabilitation training.All participants continue to receive usual poststroke clinical care. Physiotherapy,occupational therapy, speech therapy, convalescence care, and other rehabilitationservices may be prescribed according to clinical indication and are recorded asco‐interventions.Outcomes and analysisThe primary outcome is the CAVIDACE total direct score at 3 months after stroke,completed by a family informant. The total direct score ranges from 0 to 192, with higherscores indicating better quality of life. The corresponding CAVIDACE score obtainedapproximately 20 days after stroke is used as the baseline covariate in the primaryanalysis.Secondary outcomes are organized into two independent prespecified families. The familyassociated with computerized neuropsychological rehabilitation includes the globalneuropsychological composite score, Modified Rankin Scale, Barthel Index, andLawton‐Brody Instrumental Activities of Daily Living Scale. The family associated withstructured family psychoeducation includes the Zarit Burden Interview, Hospital Anxietyand Depression Scale Anxiety subscale, Hospital Anxiety and Depression Scale Depressionsubscale, and Beck Depression Inventory‐II.The primary analysis follows the intention‐to‐treat principle and uses an analysis ofcovariance model including the main effects of both intervention factors, baselineCAVIDACE, and the randomization stratum. The F1×F2 interaction is examined in a separateexploratory model.Exploratory biological outcomes include brain‐derived neurotrophic factor, glialfibrillary acidic protein, interleukin‐6, C‐reactive protein, and S100 calcium‐bindingprotein B. Acute structural magnetic resonance imaging variables include lesion volume,lesion location, vascular territory, Oxfordshire Community Stroke Project classification,and apparent diffusion coefficient. These analyses are considered exploratory andhypothesis‐generating.A prespecified Statistical Analysis Plan defining the estimands, analysis models,handling of missing data, multiplicity, and sensitivity analyses was finalized and signedbefore database lock and before any comparative analysis of study outcomes.