Association of poststroke fatigue trajectories with cytokine polymorphims

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DESCRIPTION (provided by applicant): Every 40 seconds, someone in the United States has a stroke. Although functional recovery from stroke is quite variable, stroke continues to be the leading cause of long-term adult disability. With an aging population at increased risk of stroke and increased survival from stroke, improving functional recovery from stroke is critically important. Fatigue is a common symptom following stroke. Fatigue interferes with rehabilitation, delays recovery, decreases quality of life, and is associated with worse functional outcomes after stroke. Although fatigue generally declines within 3 months of stroke in many it can become persistent. Why persistent fatigue occurs in these patients is unclear. I propose that persistent fatigue that occurs in individuals at 3 and 6 months after stroke is related to an elevated inflammatory risk as evidenced by specific genetic polymorphisms in inflammatory cytokine genes. To test this hypothesis I plan to conduct a longitudinal, quantitative, observational study, to assess subjective fatigue and overall function in 75 individuals 1-, 2-, 3- and 6 months post stroke. Genomic DNA purified from buccal cells will be used to perform genetic analysis of promoter polymorphisms that affect expression of the inflammatory cytokines, interleukin (IL)-6, IL-12, and IL-10. Generalized linear modeling will be used to quantify associations between cytokine polymorphisms and trajectories of poststroke fatigue over time. It is hoped that study findings may support the identification of individuals at greates risk of persistent fatigue and lead to the development of targeted interventions to reduce the burden of poststroke fatigue. The investigator will have additional coursework in human genetics, neurology, and longitudinal statistical analysis, in addition to mentored training in genetic and statistical techniques to ensure adequate preparation for a successful study and an academic research career. The proposed research provides a foundation for the investigator's long-term goal to develop targeted interventions to improve functional recovery from stroke.