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.

Public Health Relevance

By shedding light on whether inflammation plays a role in poststroke fatigue, this research supports the development of therapies targeted to reduce symptom burden in stroke survivors. In addition this research will support improved education to stroke survivors and their families about persistent symptoms such as fatigue, which might decrease symptom distress.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NR013299-02
Application #
8452235
Study Section
National Institute of Nursing Research Initial Review Group (NRRC)
Program Officer
Banks, David
Project Start
2012-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$35,524
Indirect Cost
Name
Oregon Health and Science University
Department
None
Type
Schools of Nursing
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Weymann, K B; Wood, L J; Zhu, X et al. (2014) A role for orexin in cytotoxic chemotherapy-induced fatigue. Brain Behav Immun 37:84-94