Cognitive Recovery After Poststroke Delirium (RECOVER): Protocol for a Longitudinal Multimodal Study on Cognitive...

Poststroke delirium (PSD) is a severe complication in patients with acute stroke and is characterized by rapid onset fluctuating symptoms, which affect multiple domains (cognition, motor system, and sleep-wake cycle). Similar to other types of delirium, PSD is associated with longer hospitalization, higher mortality, and a higher disability rate. Behavioral studies on cognitive functioning showed significantly poorer cognitive outcomes in both patients with and without PSD compared to healthy controls. Thus, the distinction between "stroke-related" and "PSD-related" cognitive impairments remains unclear. A frequently affected and highly disabling cognitive domain is memory function. However, imaging studies, particularly task-based functional magnetic resonance imaging (MRI) studies on PSD, are currently scarce and represent a significant gap in the existing literature.

This longitudinal proof-of-concept study aims to investigate the short- and long-term effects of stroke and PSD on cognitive outcome using a multimodal approach and to outline a protocol for a repeated multimodal cognitive assessment in patients with stroke.

We developed a longitudinal study protocol to investigate short- and long-term effects of stroke and PSD on cognitive impairment and recovery. Poststroke cognitive impairment (PSCI) will be assessed in a comprehensive digital multimodal approach including a multidomain neuropsychological app to facilitate a standardized, rapid testing, particularly for long-term outcomes, as well as task-based functional MRI (introducing a modified working memory task) during the acute (prior PSD development) and postacute phase post stroke and at a 3-month follow-up. In total, 40 patients with acute stroke, divided into a PSD group and non-PSD group (control), will be examined. In the context of the proof-of-concept study, the eligibility of a modified working-memory task, an app-based neuropsychological assessment, and a multimodal MRI protocol will be evaluated. The primary endpoint is a between-group comparison of the cognitive outcome, defined as global PSCI at a 3-month follow-up. Global PSCI will be classified as normal cognitive functioning, or mild, moderate, or severe cognitive impairment, according to the performance level (norm-referenced z scores) on a multidomain neuropsychological assessment.

This study was funded in December 2023. As of May 2025, 15 patients with stroke have been included. Recruitment and data collection were initiated in June 2024 and are ongoing until December 2025. The findings are expected to be published in summer 2026.

This protocol outlines a proof-of-concept study aiming to fill a critical gap by systematically investigating cognitive functions in patients with acute stroke with and without delirium. Generating reliable preliminary data will provide essential groundwork for future large-scale research, ultimately enhancing understanding of the contribution of PSD to cognitive impairment.