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: Brain injury is researched using physical, mathematical, anatomical, and computational models. However, there has been little research to quantify the expected differences between these methods of brain injury research. The purpose of this research was to compare the brain deformation responses of identical traumatic brain injury (TBI) reconstructions, which were conducted first with Mathematical Dynamic Models (MADYMO) and then again with a Hybrid III headform. The ensuing finite element modelling was done using the University College Dublin Brain Trauma Model. The brain deformation parameters were analysed in discrete regions of interest which matched the TBI lesion as identified on computed tomography scans of the subject. The results indicated that overall the Hybrid III provided responses which were of considerably larger magnitude than the MADYMO simulation for all metrics analysed. The larger magnitude responses are likely a product of the more rigid nature of the Hybrid III in comparison to the MADYMO simulations. Interestingly, when the results are compared to the literature, the Hybrid III results match well with mild traumatic brain injury (mTBI) and TBI research, while the MADYMO simulations produce what would be considered very low local brain deformation responses for TBI lesions.International Journal of Crashworthiness 02/2014;
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ABSTRACT: Calcium ions are versatile and universal biological signaling factors that regulate numerous cellular processes ranging from cell fertilization, to neuronal plasticity that underlies learning and memory, to cell death. For these functions to be properly executed, calcium signaling requires precise regulation, and failure of this regulation may tip the scales from a signal for life to a signal for death. Disruptions in calcium channel function can generate complex multi-system disorders collectively referred to as "calciumopathies" that can target essentially any cell type or organ. In this review, we focus on the multifaceted involvement of calcium signaling in the pathophysiology of Alzheimer's disease, and summarize the various therapeutic options currently available to combat this disease. Detailing the series of disappointing AD clinical trial results on cognitive outcomes, we emphasize the urgency to design alternative therapeutic strategies if synaptic and memory functions are to be preserved. One such approach is to target early calcium channelopathies centrally linked to AD pathogenesis.European journal of pharmacology 12/2013; · 2.59 Impact Factor
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ABSTRACT: To investigate the association between traumatic brain injuries (TBIs) and the risk of young onset dementia (YOD), that is, dementia before 65 years of age. The study cohort comprised 811,622 Swedish men (mean age 5 18 years) conscripted for military service between 1969 and 1986. TBIs, dementia, and covariates were extracted from national registers. Time-dependent exposures using Cox proportional hazard regression models were evaluated. During a median follow-up period of 33 years, there were 45,249 men with at least 1 TBI in the cohort. After adjustment for covariates, 1 mild TBI (hazard ratio [HR] 5 1.0, 95% confidence interval [CI] 5 0.5–2.0), at least 2 mild TBIs (HR 5 2.5, 95% CI 5 0.8–8.1), or 1 severe TBI (HR 5 0.7, 95% CI 5 0.1–5.2) were not associated with Alzheimer dementia (AD). Other types of dementia were strongly associated with the risk of 1 mild TBI (HR 5 3.8, 95% CI 5 2.8–5.2), at least 2 mild TBIs (HR 5 10.4, 95% CI 5 6.3–17.2), and 1 severe TBI (HR 5 11.4, 95% CI 5 7.4–17.5) in age-adjusted analysis. However, these associations were largely attenuated after adjustment for covariates (1 mild TBI: HR 5 1.7; at least 2 mild TBIs: HR 5 1.7; 1 severe TBI: HR 5 2.6; p < 0.05 for all). In the present study, we found strong associations between YOD of non-AD forms and TBIs of different severity. These associations were, however, markedly attenuated after multivariate adjustment.Annals of Neurology 03/2014; 75(3):374-81. · 11.19 Impact Factor