Interventions for post-stroke cognitive impairment: a systematic review of neuroplastic mechanisms, comparative efficacy, and multimodal approaches.

INTRODUCTION

Post-stroke cognitive impairment (PSCI) affects 30%-70% of stroke survivors and represents a significant barrier to functional recovery and quality of life. This systematic review synthesizes current evidence on multimodal interventions targeting neuroplastic mechanisms to ameliorate cognitive dysfunction following stroke.

METHODS

Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials published between January 2020 and October 2025. Forty-seven studies met inclusion criteria, encompassing 3,842 participants across diverse intervention modalities including non-invasive brain stimulation (transcranial direct current stimulation, repetitive transcranial magnetic stimulation), cognitive rehabilitation, virtual reality training, computer-assisted cognitive training, and combined multimodal approaches.

RESULTS

Narrative synthesis revealed that transcranial direct current stimulation combined with cognitive training consistently yielded the largest improvements in global cognitive function across included trials, followed by repetitive transcranial magnetic stimulation protocols. Several studies also explored pharmacological agents (e.g., cholinesterase inhibitors) as adjunctive components within multimodal protocols.

DISCUSSION: Neuroplasticity mechanisms underlying these improvements include enhanced synaptic plasticity, modulation of long-term potentiation, neurogenesis in perilesional regions, functional reorganization of cortical networks, and restoration of interhemispheric balance. Early intervention initiation (within 3 months post-stroke) was associated with enhanced outcomes across modalities. Virtual reality and computer-assisted training demonstrated moderate efficacy with superior patient engagement and accessibility. Evidence supports multimodal, personalized rehabilitation protocols integrating brain stimulation with behavioral interventions to optimize neuroplastic potential. Future research should evaluate combined rehabilitation approaches at the neural level, assess pharmacological treatment effects on neural plasticity, and investigate long-term maintenance of cognitive gains. This review provides evidence-based guidance for clinicians implementing neuroplasticity-informed rehabilitation strategies for post-stroke cognitive recovery.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier [CRD420261382284].