Genetic and cytokine influences on cognitive recovery following traumatic brain injury: A longitudinal study

Title : Genetic and cytokine influences on cognitive recovery following traumatic brain injury: A longitudinal study

Abstract:

Objectives: This study aimed to investigate the relationship between APOE genotype, cytokine levels, and cognitive outcomes in patients recovering from traumatic brain injury (TBI). The objectives were to assess the impact of APOE ε2 and ε4 variants on cytokine profiles and determine their association with cognitive recovery at multiple time points, up to one year following injury. 
Methods: A diverse cohort of 20 TBI patients with moderate to severe injuries was longitudinally assessed over a two-year period. Genetic analysis determined APOE genotype, distinguishing between ε2, ε3, and ε4 variants. Cytokine profiles were assessed through enzyme-linked immunosorbent assays (ELISA) to measure multiple cytokines, including IL-6, TNF-alpha, IL-8, and IL-1b. Cognitive outcomes were evaluated using neuropsychological assessments, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment (MoCA).
Results: APOE genotype significantly influenced cytokine levels, with ε2 carriers demonstrating lower pro-inflammatory cytokine levels, including IL-6 and TNF-alpha, compared to ε4 carriers. ε4 carriers exhibited a more pronounced neuroinflammatory profile, potentially contributing to differential cognitive recovery patterns. Spearman's and Pearson's correlations unveiled complex associations between cytokine levels and cognitive domains. Pro-inflammatory cytokines, such as IL-8 and IL-1b, showed mixed correlations with cognitive outcomes, while anti-inflammatory cytokines like IL-10 displayed limited associations. Longitudinal analyses revealed dynamic relationships between cytokines and cognition, emphasizing the evolving nature of TBI recovery.
Conclusions: This study elucidates the intricate interplay between APOE genotype, cytokine profiles, and cognitive outcomes in TBI patients. APOE ε2 and ε4 variants were associated with distinct cytokine profiles, potentially contributing to differential cognitive trajectories. Pro-inflammatory cytokines demonstrated complex relationships with cognitive domains, suggesting that neuroinflammation plays a nuanced role in TBI recovery. These findings underscore the importance of considering genetic and cytokine factors in tailoring personalized rehabilitation strategies for TBI patients. Further research is warranted to delineate the mechanisms driving these relationships and to translate these insights into improved clinical interventions for TBI recovery.

Biography:

Dr. Emily Rosario, PhD is a Neuroscientist and current Director of the Research Institute at Casa Colina Hospital and Centers for Healthcare. She has over 15 years of research experience in rehabilitation medicine, age-related disease and dysfunction, neurologic disorders, and endocrine dysfunction at both the basic science and clinical level. She has nearly 40 peer-reviewed publications in the areas of neuroscience, neurologic disorders, and rehabilitation including several publications in high impact journals such as the Journal of the American Medical Association (JAMA), the Journal of Neuroscience, Neurology, and Frontiers in Neurendocrinology. Dr. Rosario has received several awards and grants funding her research from the Alzheimer’s Association, the UniHealth Foundation, and the National Institutes of Health (NIH), specifically, the Eye Institute, National Institute of Aging, and National Institute of Neurological Disorders and Stroke. She has been invited to present her work both nationally and internationally at over 50 conferences including the International conference for Alzheimer’s disease, World Congress on Traumatic Brain Injury, and Society for Neuroscience. As Director of Research at Casa Colina Hospital, Dr. Rosario works with numerous clinicians including physicians, audiologists, neuropsychologists, physical, occupational, and speech therapists on over a dozen diverse research studies. The research, all neurologic or rehabilitation focused, ranges from outcome-based research studies to retrospective, observational, and randomized controlled clinical trials. In addition, she collaborates with several academic and research institutions including Cedar-Sinai, UCLA, USC, and the California Institute of Technology on a number of research projects. As part of her collaboration with academic institutions she has trained and supervised over 25 research students on various clinical research studies including acting as the primary mentor for senior research or honors dissertation projects. She has also served as a guest lecturer at USC, UCLA, University of LaVerne, and the Claremont Colleges, on a variety of topics including Neuroscience, Neurodegenerative diseases, Biology of Aging, Neuroendocrinology, Metabolic syndrome, Research Methods, and Neuropsychology.