Abstract
BackgroundStroke 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 long-term post-stroke cognitive trajectories in individuals with ischemic stroke.MethodsStrokeCog 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.DiscussionStrokeCog will provide novel insight into the relationships between immune events and cognitive change late after stroke.
Highlights
Stroke increases the risk of cognitive impairment even several years after the stroke event
Post-stroke dementia is more prevalent with age [5], and is a subset of vascular dementia that may be uniquely related to inflammation
Previous research from our group demonstrated that in animal models, stroke triggers a long-lasting adaptive immune response that is required for post-stroke dementia [17]
Summary
Stroke increases the risk of cognitive impairment even several years after the stroke event. 800,000 individuals in the United States sustain a stroke each year [1] It is well-known that stroke can be associated with acute cognitive effects, for which some degree of recovery is to be expected. Systemic inflammation is implicated in age-related cognitive decline [13, 14] and in vascular dementia [15, 16]. Autoantibodies to myelin basic protein are associated with worsening cognitive trajectory in the first year after stroke [18] In both animals and humans, an infection in the days after stroke boosts harmful autoimmunity and worsens overall outcomes, likely by acting as an adjuvant to brain antigens released into the circulation by stroke [19, 20]. The associations between systemic inflammation and longer-term post-stroke cognitive decline have not been comprehensively studied
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