Journal Article

Chronic neuropathologies of single and repetitive TBI: substrates of dementia?

Stewart, William, Smith, Douglas H., Johnson, Victoria E.

2013

Overview

The link between traumatic brain injury and dementia has long been recognized, and has gained additional prominence through recent high-profile reports of chronic traumatic encephalopathy (CTE) in athletes exposed to repetitive head injury. In this Review, Smith et al . outline the neuropathological features of CTE that are thought to contribute to cognitive impairment, and discuss the work that remains to be done to define CTE as a distinct disease entity. Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of 'chronic traumatic encephalopathy' (CTE) in athletes exposed to repetitive head injury. Originally termed 'dementia pugilistica' and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI. Key Points Traumatic brain injury (TBI) represents the strongest environmental risk factor for dementia Current evidence indicates a possible 'dose' and frequency-dependent association between TBI and risk of neurodegenerative disease The human pathology of survival from TBI is best described as a 'polypathology', featuring amyloid-β, tau and TDP-43 pathologies, together with white matter degradation, neuronal loss and neuroinflammation The chronic pathologies following single and repetitive injuries show similarities, although comparative studies are lacking at present TBI may offer an opportunity for better understanding of the evolution of pathologies in a wider range of neurodegenerative diseases There is an urgent need to extend existing tissue banks dedicated to TBI and establish further networked archives to provide broad international research access

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1689/132 / 631/378/1689/2609 / 692/499 / 692/699/375/1345 / Aged / Athletic Injuries - complications / Boxing / Brain - metabolism / Brain - pathology / Brain injuries / Brain Injuries - complications / Brain Injuries - epidemiology / Brain Injuries - etiology / Brain Injuries - pathology / Care and treatment / Chronic Disease / Chronic traumatic encephalopathy / Complications and side effects / Dementia / Dementia - epidemiology / Dementia - etiology / Disease Progression / Football / Humans / Male / Medicine / Medicine & Public Health / Neurofibrillary Tangles - pathology / Neurology / Pathology / review-article / Risk Factors / Traumatic brain injury / Young Adult