JMIR Publications

ABSTRACT

Background:

Post-stroke delirium (PSD) is a severe complication in acute stroke patients and is characterized by rapid onset fluctuating symptoms, which affect multiple domains (cognition, motor system, 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 PSD and non-PSD stroke patients 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 are memory functions. However, imaging studies, particularly task-based functional MRI studies on PSD, are currently scarce and represent a significant gap in the existing literature.

Objective:

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 stroke patients.

Methods:

We developed a longitudinal study protocol to investigate short- and long-term effects of stroke and PSD on cognitive impairment and recovery. Post-stroke cognitive impairment (PSCI) will be assessed in a comprehensive digital multimodal approach including a multi-domain neuropsychological app to facilitate a standardized, rapid testing, particularly for long-term outcomes, as well as tasked-based functional MRI (introducing a modified working memory task) during the acute (prior PSD development) and post-acute phase post-stroke and at 3-month follow-up. In total 40 acute stroke patients, 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 3-months 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 multi-domain neuropsychological assessment.

Results:

This study was funded in December 2023. Recruitment and data collection was initiated in June 2024 and are ongoing until December 2025. Findings are expected to be published in summer 2026.

Conclusions:

This protocol outlines a proof-of-concept study aiming to fill a critical gap by systematically investigating cognitive functions in acute stroke patients with and without delirium. Generating of reliable preliminary data will provide essential groundwork for future large-scale research, ultimately enhancing understanding the contribution of PSD to cognitive impairment. Clinical Trial: ClinicalTrials.gov: NCT06680336.