Sports concussions and aging: a neuroimaging investigation.

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

[1]  N. Nakayama,et al.  Evidence for white matter disruption in traumatic brain injury without macroscopic lesions , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[2]  J. Langlois,et al.  The Epidemiology and Impact of Traumatic Brain Injury: A Brief Overview , 2006, The Journal of head trauma rehabilitation.

[3]  L. Engebretsen,et al.  Consensus statement on concussion in sport--the 4th International Conference on Concussion in Sport held in Zurich, November 2012. , 2013, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[4]  R. Buckner,et al.  Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD , 2005, Neurology.

[5]  P. Hof,et al.  Review: Contact sport‐related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates , 2011, Neuropathology and applied neurobiology.

[6]  W M Brooks,et al.  Magnetic resonance spectroscopy in traumatic brain injury. , 2001, The Journal of head trauma rehabilitation.

[7]  Roberto Sorge,et al.  Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. , 2010, Brain : a journal of neurology.

[8]  D. Bennett,et al.  Vitamin E and donepezil for the treatment of mild cognitive impairment. , 2005, The New England journal of medicine.

[9]  J. Borg,et al.  Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. , 2004, Journal of rehabilitation medicine.

[10]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[11]  R. Hébert,et al.  Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. , 2002, American journal of epidemiology.

[12]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[13]  M. Putukian,et al.  A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion. , 2011, Journal of neurotrauma.

[14]  J. Pettegrew,et al.  Quantitative 1H and 31P MRS of PCA extracts of postmortem Alzheimer's disease brain , 1996, Neurobiology of Aging.

[15]  D D Blatter,et al.  Nonspecific white matter degeneration following traumatic brain injury , 1995, Journal of the International Neuropsychological Society.

[16]  J. Price,et al.  Mild cognitive impairment represents early-stage Alzheimer disease. , 2001, Archives of neurology.

[17]  P Sachdev,et al.  Magnetic resonance spectroscopy in AD , 2001, Neurology.

[18]  Dwight Parkinson,et al.  Cumulative Effects of Concussion in High School AthletesIn Reply , 2003 .

[19]  L. Thal,et al.  Alzheimer’s disease can be accurately diagnosed in very mildly impaired individuals , 2002, Neurology.

[20]  T. Perneger What's wrong with Bonferroni adjustments , 1998, BMJ.

[21]  Timo Kurki,et al.  Cognitive functions in relation to MRI findings 30 years after traumatic brain injury , 2005, Brain injury.

[22]  Pierre Jolicoeur,et al.  Long-term electrophysiological changes in athletes with a history of multiple concussions , 2007, Brain injury.

[23]  Nicholas Stergiou,et al.  A Nonlinear Dynamic Approach for Evaluating Postural Control , 2005, Sports medicine.

[24]  C. Jack,et al.  Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment , 2008, Neurology.

[25]  Ranjan Duara,et al.  Semantic interference deficits and the detection of mild Alzheimer's disease and mild cognitive impairment without dementia , 2004, Journal of the International Neuropsychological Society.

[26]  E. Barbeau,et al.  Evaluation of visual recognition memory in MCI patients , 2004, Neurology.

[27]  Pierre Jolicoeur,et al.  Cumulative effects of concussions in athletes revealed by electrophysiological abnormalities on visual working memory , 2011, Journal of clinical and experimental neuropsychology.

[28]  N Butters,et al.  Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type. , 1992, Archives of neurology.

[29]  A. McKee,et al.  Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury , 2009, Journal of neuropathology and experimental neurology.

[30]  Jennifer L. Whitwell,et al.  Hippocampal volumes, proton magnetic resonance spectroscopy metabolites, and cerebrovascular disease in mild cognitive impairment subtypes. , 2008, Archives of neurology.

[31]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[32]  John S. Allen,et al.  Normal neuroanatomical variation due to age: The major lobes and a parcellation of the temporal region , 2005, Neurobiology of Aging.

[33]  G. Will “Punch Drunk” , 1939 .

[34]  J. Kelly,et al.  Traumatic brain injury and concussion in sports. , 1999, JAMA.

[35]  H. Vankova Mini Mental State , 2010 .

[36]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[37]  R. Cantu,et al.  Long-term and Cumulative Effects of Sports Concussion on Motor Cortex Inhibition , 2008 .

[38]  A. Blamire,et al.  Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. , 2000, Brain : a journal of neurology.

[39]  M. Gaetz,et al.  Electrophysiological evidence for the cumulative effects of concussion. , 2000, Brain injury.

[40]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[41]  Alain Ptito,et al.  Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms. , 2008, Archives of general psychiatry.

[42]  Agatha D. Lee,et al.  Acute and chronic changes in diffusivity measures after sports concussion. , 2011, Journal of neurotrauma.

[43]  N. Schuff,et al.  Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria , 2010, Neurobiology of Aging.

[44]  S. Tremblay,et al.  Neurometabolic changes in the acute phase after sports concussions correlate with symptom severity. , 2010, Journal of neurotrauma.

[45]  Sterling C. Johnson,et al.  Longitudinal changes in patients with traumatic brain injury assessed with diffusion-tensor and volumetric imaging , 2008, NeuroImage.

[46]  O Henriksen,et al.  In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. , 1993, Magnetic resonance imaging.

[47]  Joanna M. Wardlaw,et al.  A systematic review of brain metabolite changes, measured with 1H magnetic resonance spectroscopy, in healthy aging , 2009, Neurobiology of Aging.

[48]  Jiri Dvorak,et al.  Consensus Statement on Concussion in Sport: the 3rd International Conference on Concussion in Sport held in Zurich, November 2008 , 2009, British Journal of Sports Medicine.

[49]  Bruno Kopp,et al.  Fractionating the Neural Mechanisms of Cognitive Control , 2006, Journal of Cognitive Neuroscience.

[50]  C. Jack,et al.  Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI , 2005, Neurology.

[51]  Cyril H Wecht,et al.  CHRONIC TRAUMATIC ENCEPHALOPATHY IN A NATIONAL FOOTBALL LEAGUE PLAYER: PART II , 2005, Neurosurgery.

[52]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[53]  A. Dale,et al.  Effects of age on volumes of cortex, white matter and subcortical structures , 2005, Neurobiology of Aging.

[54]  M. Kamboh,et al.  Emerging Histomorphologic Phenotypes of Chronic Traumatic Encephalopathy in American Athletes , 2011, Neurosurgery.

[55]  J Messier,et al.  Brain Function Decline in Healthy Retired Athletes who Sustained their Last Sports Concussion in Early Adulthood , 2009, NeuroImage.

[56]  S. Marshall,et al.  Association between Recurrent Concussion and Late-Life Cognitive Impairment in Retired Professional Football Players , 2005, Neurosurgery.

[57]  Stephen K Fisher,et al.  Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance , 2002, Journal of neurochemistry.

[58]  S. Chantal,et al.  Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease , 2004, Brain Research.

[59]  Gerald F. Tremblay Neuropathology , 1989, Neurology.

[60]  D. Allsop,et al.  The occult aftermath of boxing. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[61]  D J Jenden,et al.  In vivo 1H MRS choline: correlation with in vitro chemistry/histology. , 1996, Life sciences.

[62]  C. Jack,et al.  Ventricular maps in 804 ADNI subjects: correlations with CSF biomarkers and clinical decline , 2010, Neurobiology of Aging.

[63]  Sébastien Tremblay,et al.  Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes. , 2012, Cerebral Cortex.

[64]  Kuncheng Li,et al.  Regional metabolic changes in the hippocampus and posterior cingulate area detected with 3-Tesla magnetic resonance spectroscopy in patients with mild cognitive impairment and alzheimer disease , 2009, Acta radiologica.

[65]  Steven Robbins,et al.  An unbiased iterative group registration template for cortical surface analysis , 2007, NeuroImage.

[66]  J. Polich,et al.  P3a and P3b from typical auditory and visual stimuli , 1999, Clinical Neurophysiology.

[67]  A. Dale,et al.  High consistency of regional cortical thinning in aging across multiple samples. , 2009, Cerebral cortex.

[68]  M. Shenton,et al.  Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions. , 2011, Current opinion in neurology.

[69]  J. Klein Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids , 2000, Journal of Neural Transmission.

[70]  Clifford R. Jack,et al.  Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease , 2007, Neurobiology of Aging.

[71]  Christopher J. A. Cowie,et al.  Quantitative magnetic resonance imaging in traumatic brain injury , 2012 .

[72]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[73]  R. Cantu Neurophysiological Anomalies in Symptomatic and Asymptomatic Concussed Athletes , 2007 .

[74]  M. Raichle,et al.  Detection of blast-related traumatic brain injury in U.S. military personnel. , 2011, The New England journal of medicine.

[75]  D. Hovda,et al.  The Neurometabolic Cascade of Concussion. , 2001, Journal of athletic training.