Neuroimaging of Cognitive Dysfunction and Depression in Aging Retired National Football League Players A Cross-sectional Study

JAMA neurology 01/2013; 70(3):1-10. DOI: 10.1001/2013.jamaneurol.340
Source: PubMed


OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.

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Available from: Jeremy F Strain, Mar 24, 2014
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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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    • "Therefore, whole-brain white matter anomalies patterns affecting specific tracts can be related to particular cognitive/motor impairments in clinical populations. Multiple groups trying to uncover the nature of acute and chronic symptoms in concussed athletes have applied this technique (Zhang et al., 2010; Cubon et al., 2011; Koerte et al., 2012; Chamard et al., 2013; Hart et al., 2013; Strain et al., 2013) or older techniques (Zhang et al., 2003, 2006; Chappell et al., 2006; Henry et al., 2011; Bazarian et al., 2012; Marchi et al., 2013; Virji-Babul et al., 2013). Diffuse anomalies during the acute and sub-acute periods are described in most cases along various major interhemispheric, associative, and projection fibre tracts, although no consistent spatial pattern of injury seems to emerge from those studies (Gardner et al., 2012). "
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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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    • "From a neuropathological perspective, CTE is associated with the appearance of foci of hyperphosphorylated tau tangles, disseminated microgliosis and astrocytosis and progressive neurodegeneration (McKee et al. 2009, 2013; Mez et al. 2013). CTE has been linked to increased mortality, shortened life-span and increased co-morbidity of neurodegenerative [e.g., Alzheimer's and Parkinson's disease (Masel and DeWitt 2010; Guskiewicz et al. 2007a; Langlois et al. 2006; Plassman et al. 2000; Sivanandam and Thakur 2012)] and psychiatric disorders (Guskiewicz et al. 2005, 2007a; De Beaumont et al. 2009, 2012; Rao et al. 2010; Hart et al. 2013; Mez et al. 2013)]. CTE may also reflect the culmination of long-term rmTBI (Omalu et al. 2005; McKee et al. 2009; Gavett et al. 2011). "
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    ABSTRACT: Sports-related head impact and injury has become a very highly contentious public health and medico-legal issue. Near-daily news accounts describe the travails of concussed athletes as they struggle with depression, sleep disorders, mood swings and cognitive problems. Some of these individuals have developed chronic traumatic encephalopathy, a progressive and debilitating neurodegenerative disorder. Animal models have always been an integral part of the study of traumatic brain injury in humans but, historically, they have concentrated on acute, severe brain injuries. This review will describe a small number of new and emerging animal models of sports-related head injury that have the potential to increase our understanding of how multiple mild head impacts, starting in adolescence, can have serious psychiatric, cognitive and histopathological outcomes much later in life. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 02/2014; 129(6). DOI:10.1111/jnc.12690 · 4.28 Impact Factor
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