Neurodegeneration and Dementia following Traumatic Brain Injury

Abstract

Emerging evidence from large population cohorts, both in the civilian and military settings, shows that a single event of traumatic brain injury (TBI) is associated with an increased incidence of Alzheimer’s disease (AD) and other dementias. Furthermore, although yet controversial, selected athletes sustaining repeated mild TBIs are at risk of developing mild cognitive impairment, earlier onset of Alzheimer’s disease, and plausibly tauopathy, known as chronic traumatic encephalopathy (CTE). In the brains of long-term survivors of TBI, there is evidence of increased deposition of amyloid-beta (Aβ) as well as tau aggregates. Also, Aβ aggregates as well as their neurotoxic predecessors, the Aβ protofibrils and Aβ oligomers, are found within the first post-injury week in surgically resected contused tissue. Finally, in addition to factors linked to AD and CTE, a link to other neurodegenerative disorders such as frontotemporal dementia, cerebral amyloid angiopathy, and Parkinson’s disease is suggested. Although the mechanisms linking TBI to neurodegeneration are far from established, axonal pathology and neuroinflammation may be key pathological contributors to the accumulation of factors associated with neurodegeneration. In this chapter, the current evidence for the association between TBI and neurodegeneration is summarized.