Affiliations: [a] Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| [b] Department of Neurology, Neurobehavior Unit, V.A. Greater Los Angeles Healthcare System, Los Angeles, CA, USA
Correspondence:
[*]
Correspondence to: Mario F. Mendez, MD, PhD, Neurobehavior Unit (691/116AF), V.A. Greater Los Angeles Healthcare Center, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA. Tel.: +1 310 478 3711/Ext. 42696; Fax: +1 310 268 4181; E-mail: mmendez@UCLA.edu.
Abstract: There is a long history linking traumatic brain injury (TBI) with the development of dementia. Despite significant reservations, such as recall bias or concluding causality for TBI, a summary of recent research points to several conclusions on the TBI-dementia relationship. 1) Increasing severity of a single moderate-to-severe TBI increases the risk of subsequent Alzheimer’s disease (AD), the most common type of dementia. 2) Repetitive, often subconcussive, mild TBIs increases the risk for chronic traumatic encephalopathy (CTE), a degenerative neuropathology. 3) TBI may be a risk factor for other neurodegenerative disorders that can be associated with dementia. 4) TBI appears to lower the age of onset of TBI-related neurocognitive syndromes, potentially adding “TBI cognitive-behavioral features”. The literature further indicates several specific risk factors for TBI-associated dementia: 5) any blast or blunt physical force to the head as long as there is violent head displacement; 6) decreased cognitive and/or neuronal reserve and the related variable of older age at TBI; and 7) the presence of apolipoprotein E ɛ4 alleles, a genetic risk factor for AD. Finally, there are neuropathological features relating TBI with neurocognitive syndromes: 8) acute TBI results in amyloid pathology and other neurodegenerative proteinopathies; 9) CTE shares features with neurodegenerative dementias; and 10) TBI results in white matter tract and neural network disruptions. Although further research is needed, these ten findings suggest that dose-dependent effects of violent head displacement in vulnerable brains predispose to dementia; among several potential mechanisms is the propagation of abnormal proteins along damaged white matter networks.
