Neuroimaging of cognitive dysfunction due to soccer heading-related brain injury

Michael L. Lipton, M.D., Ph.D.

Albert Einstein College of Medicine

Deparment of Radiology, Department of Psychiatry and Behavioral Sciences, Department of Neuroscience
Funded in October, 2012: $200000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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Using imaging to develop safe “heading” guidelines for soccer players

Investigators will use diffusion tensor imaging (DTI), cognitive testing and gene studies to determine levels of sub-concussive head injury from soccer “heading” that increase the risk for adverse brain and cognitive functioning, and identify factors that may increase this risk.

Traumatic brain injury (TBI) in athletes playing football, boxing, soccer or other sports is now recognized as a major health issue. For instance, soccer’s 24 million players in this country are at risk of incurring mild TBI from “heading”, using their unprotected head to deflect and advance the ball. The investigators’ preliminary studies in amateur players suggest that those heading above a threshold of 1,000 times per year may be at increased risk for damage to the brain’s white matter (nerve cell axons that connect brain regions) and cognitive impairment. Additionally, certain factors may increase that risk. Specifically, the investigators hypothesize that:


1) cumulative exposure to heading over the previous year will predict white matter changes that are characteristic of traumatic axonal injury, related cognitive impairments and post--concussion symptoms; and

2) Individual characteristics, such as having the ApoE4 gene, which is implicated in Alzheimer’s disease, will predict a reduction in the threshold for incurring these problems.

They will enroll 250 adult amateur soccer players from among several New York City leagues. For each player, they will obtain a gene sample and information on their field position, gender, and neck length and thickness. Each player will undergo cognitive testing and DTI imaging of white matter axon tracts to establish baseline data on cognitive functioning and traumatic axonal injury associated with cumulative repetitive heading (and any concussions) to date as reflected by a questionnaire. Thereafter players will be followed for a year. They will complete a monthly Web- based questionnaire quantifying their heading. Additionally, during two months, they will record heading and post-concussive symptoms daily via an Android smart phone, to enable the investigators to determine whether the incremental value of daily assessments justifies its use for future studies. Analyses will determine:


1) The threshold level for heading that must be exceeded to result in traumatic axonal injury, impaired cognitive functioning and greater post-concussion symptoms;

2) Whether higher heading levels are associated with evidence of traumatic axonal injury, cognitive impairment and increased post-concussive symptoms; and

3) Factors,such as ApoE4 gene, body structure or player position, increase risk and reduce the heading threshold for injury.

Significance: Findings will lead to a larger study designed to result in development of guidelines for safe soccer play.

ABSTRACT

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Neuroimaging of cognitive dysfunction due to soccer heading-related brain injury

Traumatic brain injury (TBI) in athletes is a major and increasingly recognized public health problem. Its presumed pathologic basis is multifocal traumatic axonal injury (TAI), which is detected in vivo using diffusion tensor MRI (DTI) and has short-term and long-term cognitive consequences. Our preliminary studies show that some amateur soccer players head the ball with surprising  frequency, up to >5,000 per year. We also find that those who head >1,000 per year are at increased risk for structural (TAI) and functional (poorer cognitive performance) changes. We seek to characterize the levels of this subconcussive mild head injury which increase risk for adverse outcomes and by extension identify levels of heading that do not increase risk. We will also gather data toward identifying particularly vulnerable groups. We propose a cross sectional and longitudinal study of 250 adult amateur soccer players in whom we will quantify heading exposure, cognitive function and post concussion symptoms and perform high resolution DTI to assess for TAI in order to address the following specific aims: <p>Aim I (Cross-sectional): Determine the relationship of heading exposure to MRI evidence of traumatic axonal injury (TAI), cognitive function and post concussion symptoms (PCS). Hypothesis Ia: High levels of prior 12-month heading exposure, independent of recognized concussion, will be associated with evidence of TAI. Hypothesis Ib: High levels of prior 12-month heading exposure, independent of recognized concussion, will be associated with lower levels of cognitive function and an increased risk of PCS. Hypothesis Ic: ApoE4 genotype will modify heading-outcome associations in hypotheses Ia and Ib.</p> Aim II (Longitudinal): Determine the longitudinal relationships of heading to changes in TAI, cognitive function, and PCS in a prospective study. Hypothesis IIa: Greater incremental heading exposure over a 1-year interval will be associated with increased TAI, independent of recognized concussion. Hypothesis IIb: Incremental heading exposure will be associated with incremental decline in cognitive function and incremental increase in risk for PCS, independent of recognized concussion. Hypothesis IIc: ApoE4 gene carriers will show greater incremental effects of heading.        Aim III: Set the stage for a future definitive study to develop guidelines for safe soccer play. We will (1) extend our validated approach to measuring heading to include intensive exposure monitoring and symptom assessment; these methods are applicable to and will facilitate the development and implementation of guidelines; (2) gather preliminary data on the role of individual characteristics (e.g., ApoE4) as modifiers of exposure thresholds; and (3) Develop preliminary data on the role of TAI as a mediator of the exposure response relationship between heading and functional outcomes.

INVESTIGATOR BIOGRAPHIES

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Michael L. Lipton, M.D., Ph.D.

Dr. Michael L. Lipton is Associate Director of the Gruss Magnetic Resonance Research Center and Associate Professor of Radiology, Psychiatry and Behavioral Sciences and Neurosciences at Albert Einstein College of Medicine and Montefiore Medical Center. Dr. Lipton received his BA and MD degrees in the Six-Year Medical Program at Boston University and then trained in Diagnostic Radiology and Neuroradiology at Einstein-Montefiore. During his initial faculty appointment at Einstein, with the support of an NIMH career development award, Dr. Lipton completed a PhD in Neuroscience, encompassing imaging and electrophysiology. His overall field of interest is the development and application of advanced imaging methods for the delineation of structural and functional brain substrates of cognitive dysfunction and its translation to the clinic. To this end, Dr. Lipton’s lab has pioneered techniques to detect microstructural white matter abnormalities in individual patients. Dr. Lipton’s specific research focus is mild traumatic brain injury, also known as concussion. His work seeks to develop sensitive methods for the prediction of long-term adverse outcomes after concussion. These approaches will then be applied to identify high-risk individuals for novel therapeutic interventions.