Abstract
Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), designed to address current limitations in tissue and research access and to advance understanding of the neuropathologies of TReND. As an international, multidisciplinary collaboration CONNECT-TBI brings together multiple experts across 13 institutions. In so doing, CONNECT-TBI unites the existing, comprehensive clinical and neuropathological datasets of multiple established research brain archives in TBI, with survivals ranging minutes to many decades and spanning diverse injury exposures. These existing tissue specimens will be supplemented by prospective brain banking and contribute to a centralized route of access to human tissue for research for investigators. Importantly, each new case will be subject to consensus neuropathology review by the CONNECT-TBI Expert Pathology Group. Herein we set out the CONNECT-TBI program structure and aims and, by way of an illustrative case, the approach to consensus evaluation of new case donations.
Highlights
There are ongoing efforts to characterize the late effects of traumatic brain injury (TBI) [18]
From each CONNECT-TBI center, standardized common data elements (CDE) and unique data elements (UDE) on each case are being collated to the central CONNECT-TBI archive dataset to include, where available: patient demographics; TBI injury details including mechanism, severity, medical interventions and survival interval; clinical recovery; documented known medical comorbidities; tissue samples archived; and results of neuropathological assessments
In year 1 of CONNECT-TBI, a total of 141 cases have been accrued across centers: 36 from individuals with a history of TBI and/or exposure to repetitive head impacts, the remainder as non-TBI associated neurodegenerative disease
Summary
There are ongoing efforts to characterize the late effects of traumatic brain injury (TBI) [18]. Attention has focused on participation in contact sports and risk of the specific neurodegenerative disease, chronic traumatic encephalopathy (CTE). Smith et al acta neuropathol commun (2021) 9:32 population, nor is the risk of late neurodegeneration after TBI exclusively CTE [2]. An estimated 3–10% of dementia in the community is thought to be influenced by prior exposure to TBI [9, 14, 24]. Despite this we know remarkably little about the pathophysiology and pathologies of TBI-related neurodegeneration (TReND), within which CTE represents just one of several late consequences of TBI [25].
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