Consider the influence of injury type and survival interval on cTBI neuropathology

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Research Project 3 SUMMARY There is growing concern over the association between exposure to traumatic brain injury (TBI) and increased risk of a variety of neuropsychiatric and neurocognitive outcomes, in particular those linked to participation in contact sports. Moreover, compelling epidemiological data indicates severe TBI as an important environmental risk factor for dementia with best current estimates suggesting that between 5 and 15% of all dementia may be TBI related. Both historically and currently, TBI-associated dementia has been presumptively subdivided based on whether it follows a single, moderate or severe TBI or repetitive, mild TBI. However, over the last decade, autopsy studies have revealed complex and overlapping pathologies in individuals across the spectrum of injury exposure. Critically, there is also an incomplete understanding of the extent and distribution of TBI related neurodegeneration (TReND) pathology required to produce neurological dysfunction, the spectrum of symptoms associated with this pathology, or its relationship with wider neurodegenerative disease. As such, there is a pressing need to perform unbiased, comprehensive and robust evaluations of the complete spectrum of TReND pathologies in comparison with patient associated variables and clinical outcomes. We will use comprehensive datasets of the extensive archive of case material from chronic TBI (~850 existing and the predicted additional ~450 new chronic TBI) and matched controls made possible via this CONNECT-TBI Program. Examining these unique tissue resources and linked clinical datasets offers an unrivalled opportunity to link comprehensive outcomes and assessments with neuropathological observations. We propose to 1) examine the influence of injury variables, and 2) Determine the association between neuropathological burden and antemortem clinicopathologic presentation of chronic TBI.