A longitudinal study of the post-stroke immune response and cognitive functioning: the StrokeCog study protocol

Abstract

Background: Stroke increases the risk of cognitive impairment even several years after the stroke event. The exact mechanisms of post-stroke cognitive decline are unclear, but the immunological response to stroke might play a role. The aims of the StrokeCog study are to examine the associations between immunological responses and longterm post-stroke cognitive trajectories in individuals with ischemic stroke. Methods: StrokeCog is a single-center, prospective, observational, cohort study. Starting 6-12 months after stroke, comprehensive neuropsychological assessment, plasma and serum, and psychosocial variables will be collected at up to 4 annual visits. Single cell sequencing of peripheral blood monocytes and plasma proteomics will be conducted. The primary outcome will be the change in global and domain-specific neuropsychological performance across annual evaluations. To explain the differences in cognitive change amongst participants, we will examine the relationships between comprehensive immunological measures and these cognitive trajectories. It is anticipated that 210 participants will be enrolled during the first 3 years of this 4-year study. Accounting for attrition, an anticipated final sample size of 158 participants with an average of 3 annual study visits will be available at the completion of the study. Power analyses indicate that this sample size will provide 90% power to detect an average cognitive change of at least 0.23 standard deviations in either direction. Discussion: StrokeCog will provide novel insight into the relationships between immune events and cognitive change late after stroke.

FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke

“…In line with our protocol, DISCOVERY 24 also includes MRI and blood-based protein biomarkers, whereas STROKE-Cog has a focus on circulating blood biomarkers of immunological responses. 23 R4VaD 26 is mainly focused on dementia after stroke and includes blood biomarkers, whereas OX-CHRONIC 22 includes neuroimaging, but not biomarkers.…”

“…We have in line with the previously mentioned R4VaD 26 study decided to include participants with aphasia and encourage them to complete the study protocol, if possible, while other ongoing studies have decided to exclude patients with aphasia. 23 …”

Evidence of aberrant anti-Epstein-Barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue

“…The StrokeCog study is a longitudinal cohort study aiming to investigate the post-stroke immune response and cognitive functioning over the course of stroke recovery (29). Participants included in the parent study had ischemic strokes that were confirmed by MRI or CT scan, were over the age of 25, were able to return for annual follow-up visits, and had fluency in English.…”

The 2022 FASEB virtual Catalyst Conference on B Cells in Injury and Regeneration, March 30, 2022

“…Buckwalter shared the design of an ongoing clinical study at Stanford Hospital which is aimed at linking immunological responses to stroke with longterm post-stroke cognitive trajectories. 12 Samples are collected from patients and participants longitudinally, and immune profiling of peripheral blood mononuclear cells and plasma proteomics are used for analysis. Preliminary data indicate that numerous proteins associated with immunomodulation are significantly altered in the plasma of enrolled patients confirmed to have had an acute ischemic stroke.…”

“…Buckwalter's group is actively investigating peripheral immune signatures after stroke that may be associated with future cognitive deterioration. Buckwalter shared the design of an ongoing clinical study at Stanford Hospital which is aimed at linking immunological responses to stroke with long‐term post‐stroke cognitive trajectories 12 . Samples are collected from patients and participants longitudinally, and immune profiling of peripheral blood mononuclear cells and plasma proteomics are used for analysis.…”