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Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential con...

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Autores principales: Graham, Neil SN, Sharp, David J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860906/
https://www.ncbi.nlm.nih.gov/pubmed/31542723
http://dx.doi.org/10.1136/jnnp-2017-317557
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author Graham, Neil SN
Sharp, David J
author_facet Graham, Neil SN
Sharp, David J
author_sort Graham, Neil SN
collection PubMed
description Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss.
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spelling pubmed-68609062019-12-03 Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia Graham, Neil SN Sharp, David J J Neurol Neurosurg Psychiatry Neurodegeneration Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss. BMJ Publishing Group 2019-11 2019-09-21 /pmc/articles/PMC6860906/ /pubmed/31542723 http://dx.doi.org/10.1136/jnnp-2017-317557 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Neurodegeneration
Graham, Neil SN
Sharp, David J
Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title_full Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title_fullStr Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title_full_unstemmed Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title_short Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
title_sort understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia
topic Neurodegeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860906/
https://www.ncbi.nlm.nih.gov/pubmed/31542723
http://dx.doi.org/10.1136/jnnp-2017-317557
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