Prognostic-factors for neurodegeneration in chronic moderate-to-severe traumatic brain injury: a systematic review protocol

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Recently, a paradigm shift in our understanding of moderate-to-severe TBI has led to its reconceptualization as a progressive neurodegenerative disorder. Widespread progressive atrophy is observed in the months and years post-injury, long after the acute effects of the injury have resolved. Some studies have begun to examine prognostic demographic, injury-related, and post-injury risk factors that contribute to these declines. A synthesis of this information, and in particular, an increased understanding of post-injury factors that may be modifiable, would improve our ability to design interventions to reduce neurodegeneration in moderate-to-severe TBI. This systematic review aims to identify prognostic factors for neural deterioration in moderate-to-severe TBI, and thereby inform future intervention research in this population. METHODS: This review protocol was informed by and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines. Search strategies (designed to identify literature on prognostic factors of neurodegeneration in adults with moderate-to-severe TBI) optimized for MEDLINE, EMBASE PsychINFO, CINAHL, SportDiscus, and Cochrane Central Register of Controlled Trials will be developed with the assistance of a health sciences librarian. Retrieved studies will be screened by two team members. Studies must report on longitudinal neuroimaging (i.e., two or more scans in the same cohort) or neuroimaging in a cross-sectional study and potential prognostic factors for neurodegeneration, such as demographics (e.g., gender, age, education), injury (e.g., severity, etiology), or post-injury characteristics (e.g., type and length of therapy, activity level, mood). DISCUSSION: By identifying prognostic factors for neurodegeneration, this systematic review can help inform injury management, as well as intervention research designed to offset the effects of modifiable prognostic factors, such as low levels of cognitive or physical activity. In turn, this systematic review can increase our understanding of how to improve outcome following moderate-to-severe TBI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122389