Cognitive decline in older adults with a history of traumatic brain injury

Traumatic Brain Injury Research Laboratory, Kessler Foundation, West Orange, NJ, USA.
The Lancet Neurology (Impact Factor: 21.9). 12/2012; 11(12):1103-12. DOI: 10.1016/S1474-4422(12)70226-0
Source: PubMed


Traumatic brain injury (TBI) is an important public health problem with potentially serious long-term neurobehavioural sequelae. There is evidence to suggest that a history of TBI can increase a person's risk of developing Alzheimer's disease. However, individuals with dementia do not usually have a history of TBI, and survivors of TBI do not invariably acquire dementia later in life. Instead, a history of traumatic brain injury, combined with brain changes associated with normal ageing, might lead to exacerbated cognitive decline in older adults. Strategies to increase or maintain cognitive reserve might help to prevent exacerbated decline after TBI. Systematic clinical assessment could help to differentiate between exacerbated cognitive decline and mild cognitive impairment, a precursor of Alzheimer's disease, with important implications for patients and their families.

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    • "Athletes involved in high impact sports also show evidence of disproportionate cortical thinning and lateral ventricle enlargement, neurometabolic imbalance (Tremblay et al., 2013), abnormal cerebral blood perfusion , (Hart et al., 2013), decreased white matter integrity (i.e. fractional anisotropy) (Hart et al., 2013; Tremblay et al., 2014), as well as accelerated motor and cognitive function decline (De Beaumont et al., 2009; Moretti et al., 2012) beyond what is observed with ageing in otherwise comparable peers. Some of the changes to white matter are similar to those that have been described as occurring with ageing (Nomura et al., 1994; Courchesne et al., 2000; Nusbaum et al., 2001; Salat et al., 2005a, b; Burzynska et al., 2010; Westlye et al., 2010; Lebel et al., 2012) suggesting that a history of blunt head trauma may exacerbate any pathological burden typically associated with the ageing process. "
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    ABSTRACT: Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure-one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan-is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a 'dose-response' relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. Published by Oxford University Press on behalf of the Guarantors of Brain 2015. This work is written by US Government employees and is in the public domain in the US.
    Brain 06/2015; 138(Pt 8). DOI:10.1093/brain/awv139 · 9.20 Impact Factor
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    • "Traumatic brain injury (TBI) remains a major cause of morbidity, mortality and long-term disability in children and young adults [1], [2]. It imposes a significant threat to the lives of patients, remains a profound and long-lasting social and economic consequence and is poorly treated by currently available drugs [2], [3]. "
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    ABSTRACT: Various solutions are utilized widely for the isolation, harvesting, sorting, testing and transplantation of neural stem cells (NSCs), whereas the effects of harvesting media on the biological characteristics and repair potential of NSCs remain unclear. To examine some of these effects, NSCs were isolated from cortex of E14.5 mice and exposed to the conventional harvesting media [0.9% saline (Saline), phosphate-buffered saline (PBS) or artificial cerebrospinal fluid (ACSF)] or the proliferation culture medium (PCM) for different durations at 4°C. Treated NSCs were grafted by in situ injection into the lesion sites of traumatic brain injury (TBI) mice. In vitro, harvesting media-exposed NSCs displayed time-dependent reduction of viability and proliferation. S phase entry decreased in harvesting media-exposed cells, which was associated with upregulation of p53 protein and downregulation of cyclin E1 protein. Moreover, harvesting media exposure induced the necrosis and apoptosis of NSCs. The levels of Fas-L, cleaved caspase 3 and 8 were increased, which suggests that the death receptor signaling pathway is involved in the apoptosis of NSCs. In addition, exposure to Saline did not facilitate the neuronal differentiation of NSCs, suggesting that Saline exposure may be disadvantageous for neurogenesis. In vivo, NSC-mediated functional recovery in harvesting media-exposed NSC groups was notably attenuated in comparison with the PCM-exposed NSC group. In conclusion, harvesting media exposure modulates the biological characteristics and repair potential of NSCs after TBI. Our results suggest that insight of the effects of harvesting media exposure on NSCs is critical for developing strategies to assure the successful long-term engraftment of NSCs.
    PLoS ONE 09/2014; 9(9):e107865. DOI:10.1371/journal.pone.0107865 · 3.23 Impact Factor
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    • "This interpretation would be in line with findings of exacerbated cortical thinning and ventricular expansion with advancing age in the same sample of former concussed athletes (Tremblay et al., 2013). Overall, these results provide support for the notion that structural injury from TBI, even if not grossly apparent, might reduce the resilience of the brain and expedite the degenerative effects of ageing (Moretti et al., 2012). The consequence of this in practical terms may be that those individuals who have been concussed may experience age-related cognitive alterations earlier in life. "
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    ABSTRACT: Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.
    Brain 09/2014; 137(11):2997-3011. DOI:10.1093/brain/awu236 · 9.20 Impact Factor
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