Early Neuropsychological Rehabilitation and Family Psychoeducation After Ischemic Stroke

Overview

Cognitive impairment and reduced quality of life are frequent consequences of ischemic stroke and can also affect family caregivers, who often assume caregiving responsibilities with limited preparation. Evidence regarding rehabilitation interventions initiated during the early poststroke period remains limited. This randomized clinical trial evaluates two independent interventions initiated after baseline assessment and randomization, approximately 20 days after the index stroke: a structured computerized neuropsychological rehabilitation program for the patient and a structured psychoeducational program for the primary family caregiver. A 2×2 factorial design allows the main effect of each intervention to be estimated within a single sample and permits an exploratory assessment of their interaction. The primary outcome is quality of life at 3 months after stroke, measured using the CAVIDACE total direct score and completed by a family informant. Secondary outcomes include cognitive performance, functional status, mood, and caregiver burden. Molecular biomarkers and acute structural neuroimaging variables are examined as exploratory outcomes.

Background and rationale Cognitive deficits are frequent after ischemic stroke and may adversely affect functional recovery, quality of life, emotional well-being, and participation in rehabilitation. Although recovery trajectories vary considerably between individuals, the early poststroke period represents an important phase of cognitive, functional, and psychosocial adaptation. Evidence regarding structured cognitive rehabilitation initiated during 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 providing ongoing support. Structured psychoeducational interventions may help caregivers understand the consequences of stroke and develop appropriate strategies for supporting recovery and adaptation. This trial evaluates both dimensions simultaneously by examining computerized neuropsychological rehabilitation directed at the patient and structured family psychoeducation directed at the primary family caregiver. Procedures Participants are recruited during the acute phase of ischemic stroke, within 96 hours of symptom onset. Baseline assessment of the primary outcome is performed approximately 20 days 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 as intravenous 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 using randomly permuted blocks of variable size. The allocation sequence is inaccessible to personnel responsible for recruitment and eligibility assessment, and the next treatment assignment cannot be anticipated. Both intervention factors begin after randomization, approximately 20 days after the index stroke, and continue for approximately 12 weeks. The primary outcome assessment is scheduled at 3 months after stroke, corresponding to 90 days ±14 days. An optional 12-month follow-up constitutes an observational extension and is not part of the primary randomized trial analysis. Participants allocated to computerized neuropsychological rehabilitation receive 24 sessions of structured computerized cognitive training using the Guttmann NeuroPersonalTrainer platform. Sessions last 45 minutes and are delivered twice weekly over approximately 12 weeks. The sequence and duration of the cognitive exercises are standardized, while task difficulty is individually adjusted by the platform according to previous performance. The intervention targets attention, processing speed, memory, executive functions, language, visuospatial abilities, and functional transfer of trained strategies. Participants not allocated to computerized neuropsychological rehabilitation receive an active digital control condition consisting of simple recreational digital activities matched in duration and frequency. These activities do not incorporate adaptive difficulty, structured therapeutic progression, or cognitive performance feedback. Primary family caregivers allocated to structured family psychoeducation receive six individual 45-minute sessions delivered by videoconference approximately every 2 weeks over 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 preserve the conceptual independence of the two factorial intervention components. Primary family caregivers not allocated to structured psychoeducation receive a brief informational leaflet at the approximately 20-day visit after randomization. The leaflet provides 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 psychoeducational techniques, or cognitive rehabilitation training. All participants continue to receive usual poststroke clinical care. Physiotherapy, occupational therapy, speech therapy, convalescence care, and other rehabilitation services may be prescribed according to clinical indication and are recorded as co-interventions. Outcomes and analysis The 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 higher scores indicating better quality of life. The corresponding CAVIDACE score obtained approximately 20 days after stroke is used as the baseline covariate in the primary analysis. Secondary outcomes are organized into two independent prespecified families. The family associated with computerized neuropsychological rehabilitation includes the global neuropsychological composite score, Modified Rankin Scale, Barthel Index, and Lawton-Brody Instrumental Activities of Daily Living Scale. The family associated with structured family psychoeducation includes the Zarit Burden Interview, Hospital Anxiety and Depression Scale Anxiety subscale, Hospital Anxiety and Depression Scale Depression subscale, and Beck Depression Inventory-II. The primary analysis follows the intention-to-treat principle and uses an analysis of covariance model including the main effects of both intervention factors, baseline CAVIDACE, and the randomization stratum. The F1×F2 interaction is examined in a separate exploratory model. Exploratory biological outcomes include brain-derived neurotrophic factor, glial fibrillary acidic protein, interleukin-6, C-reactive protein, and S100 calcium-binding protein 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 and hypothesis-generating. A prespecified Statistical Analysis Plan defining the estimands, analysis models, handling of missing data, multiplicity, and sensitivity analyses was finalized and signed before database lock and before any comparative analysis of study outcomes.