Dementia Resulting From Traumatic Brain Injury: What Is the Pathology?
ABSTRACT Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2- and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed.
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ABSTRACT: The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI). This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI.Cell reports. 09/2014;
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ABSTRACT: Despite increased interest regarding the potentially long-term negative impact of chronic traumatic brain injury, limited research has been conducted regarding such injuries and neurological outcomes in real world settings. To increase understanding regarding the rela-tionship between sparring (e.g., training under the tutelage of an experienced boxing coach for the purpose of improving skills and/or fitness) and neurological functioning, professional boxers (n = 237) who competed in Maryland between 2003 and 2008 completed mea-sures regarding sparring exposure (Cumulative Sparring Index, CSI) and performance on tests of cognition (Symbol Digit Modalities Test, SDMT) and balance (Sharpened Romberg Test, SRT). Measures were completed prior to boxing matches. Higher scores on the CSI (increased sparring exposure) were associated with poorer performance on both tests of cognition (SDMT) and balance (SRT). A threshold effect was noted regarding performance on the SDMT, with those reporting CSI values greater than about 150 experiencing a decline in cognition. A history of frequent and/or intense sparring may pose a significant risk for developing boxing associated neurological sequelae. Implementing administration of clin-ically meaningful tests before bouts, such as the CSI, SDMT, and/or the SRT, as well as documentation of results into the boxer's physicals or medical profiles may be an important step for improving boxing safety.Frontiers in Public Health 07/2014; Volume 2(Article 69):1-6.
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ABSTRACT: To estimate the number of undocumented incident traumatic brain injuries (TBIs) among active component US military personnel serving in Iraq and Afghanistan prior to policy changes implemented in late 2006 and 2010 that improved TBI documentation. Negative binomial regression was used to model monthly incident TBI counts between December 2010 and June 2012 (N = 19) and then estimate expected monthly counts of incident TBIs during 2 periods: January 2003-October 2006 and November 2006-November 2010. Monthly amputation counts from Department of Defense surveillance data were used as a proxy for changing injury rates. Monthly active component deployment estimates derived from the Congressional Research Service, Brookings Institution, and Defense Manpower Data Center were used to estimate the size of the at-risk population each month. The difference between expected monthly incident TBI counts and reported counts is presented as the estimated number of undocumented incident TBIs. The full model estimates that 21 257 active component military personnel experienced undocumented incident TBIs while deployed in Iraq or Afghanistan between January 2003 and October 2006, more than 4 times the 5272 incident TBIs documented during that period. A sizeable majority of Iraq and Afghanistan combat veterans who experienced incident TBI while deployed prior to November 2006 are likely to have had their injuries undocumented, creating challenges for clinical care, disability evaluation, and future research.The Journal of head trauma rehabilitation 05/2014; · 2.39 Impact Factor