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Abstract

Objective:

To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ.

Methods:

Forty-two former National Football League (NFL) players ages 40–69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery.

Results:

Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ.

Conclusions:

There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports.

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Letters to the Editor
29 April 2015
Author Response
Robert A. Stern
Julie M. Stamm, Yorghos Tripodis, Boston

We thank the WriteClick submitters for their comments and we are grateful for the opportunity to provide a response. Our study examined the relationship between the age of first exposure to repeated head impacts and later-life cognitive impairment in former National Football League (NFL) players ages 41-65. [1] We observed that those who began playing tackle football before age 12 performed significantly worse on measures of executive function, memory, and estimated verbal IQ compared to those who began playing tackle football at age 12 or older. [1] We will address each author's comments separately.

Maroon et al. primarily focused on the limitations to our study. We agree that, due to the inclusion of only former NFL players, the results of this study may not apply to former football players whose highest level of play was only the youth, high school, or college level. Future research should investigate this important question in these other groups. We acknowledge the limitations of the retrospective cross-sectional study design, including the inability to accurately measure the total head impacts actually incurred by our subjects. In an ideal-world study, all children would wear accurate accelerometers during all athletic involvement in order to measure "actual football incurred head impacts exclusive of other sports played." However, these were not available at the time our subjects participated in football, and they are still not widely used today. Although this is an important limitation, we did use total number of years played as a proxy for total exposure in the statistical analysis in this study, and this did not account for our results. Additionally, participation in other contact sports did not differ between those who began playing football before age 12 and those who began playing at age 12 or older in this study. We are unsure why Maroon and colleagues considered the neuropsychological tests selected for this study "suboptimal." As stated in the methods, these tests were specifically selected for the hypothesized outcomes [1] (references 14, 19-24, and 26 [1]) and are commonly used, highly accepted tests (see references 27-31 [1]). We also reported that the t-scores come from published normative data.

Furthermore, it is unclear what Maroon et al. are questioning with regard to selection of age 12, given that a large proportion of the introduction and discussion specifically details this critical information.

Maroon and colleagues suggested that "the way football was played by the study subjects in the 1960's to '80's is not representative of the improved, safer practices of modern-day youth football programs." We agree that this may be true. However, while safer practices may have been adopted by some youth football leagues, other leagues have not taken these steps. Furthermore, with increased parental pressure, television programs such as "Friday Night Tykes," [2] and websites that scout football players as early as the sixth grade, [3] it could be argued that the nature of "modern- day youth football programs" may be more intense and violent in some cases today than it was when our participants played youth football. We agree with Maroon et al. that, in an ideal world, a longitudinal study of a large number of children across multiple socioeconomic, cultural, ethnic minority, and geographic locations could be conducted with detailed examinations of the children and their parents, including "parenting styles," prior to decision-making regarding involvement in sports, then examine them again 40 years later. Unfortunately, that logistically (and financially) challenging study has yet to be conducted. We addressed some of the many potential biases and alternate explanations for the results of this study, including socioeconomic status and pre-exposure intelligence. Despite the limitations of this study that we clearly addressed, we believe that, based on our findings, it is appropriate to state that "incurring repeated head impacts during a critical neurodevelopmental period may [italics our emphasis] increase the risk of later-life cognitive impairment." We do not believe it would be appropriate to conclude definitive causation, and we state clearly in the discussion that much more research is needed and should occur before changes are made to rules and policies in youth sports.

Though Dr. Andrikopoulos did not comment on the results of our study, we thank him for his comments on our methods and literature. He began his comments by questioning our modern definition of a concussion [4] and asked: "Would a neurologist actually record this number of concussions in a patient medical record?" Robbins et al. [4] observed that, after being provided with this modern concussion definition, participants reported a two-fold increase in the number of concussions reported. This, and other evidence, [5] suggests that patients may not understand what a concussion is, and neurologists and other health care providers should provide a definition before asking patients about their concussion history. Furthermore, the clinical manifestation of more mild concussions (i.e., seeing stars), as well as subconcussive impacts are still unclear.

The disease chronic traumatic encephalopathy has been diagnosed in individuals with no reported history of concussions. [6] Therefore, we believe it may be important for health care providers to record this detailed information. We respectfully disagree with Dr. Andrikopoulos' interpretation of our referenced literature on intelligence following concussion. Reference 4 found that academic grade point averages were significantly lower for youth athletes with a history of two or more previous concussions, but without a recent concussion. Grade point average is often used as a proxy for overall intellectual functioning and is correlated with a full scale IQ testing battery. [7] Contrary to the interpretation of Dr. Andrikopoulos, reference five covers a range of severity levels of both focal injuries with "demonstrable lesions" and diffuse brain injury, and reference six was not limited to severe head injury but also included mild and moderate head injury as well. With regard to the control group, this was reported in the methods section as part of the overall DETECT study, from which the data for this study was obtained. As this study compared former NFL players who started playing tackle football prior to age 12 to former NFL players who began playing tackle football at age 12 or older, it was appropriate not to include the control group in the analysis. Furthermore, symptom validity was assessed as part of the larger neuropsychological testing battery, and this did not differ between age of first exposure groups.

Larabee and colleagues commented on our use of the WRAT-4 Reading test as an outcome measure in this study and attempted to use this test as a covariate in order to show that our results are explained by premorbid differences in intelligence. We appreciate their comments yet we believe it is appropriate to use the WRAT-4 Reading test as an outcome measure in this study. As these authors accurately state, the WRAT-4 Reading test "is often used to estimate premorbid cognitive ability due to its resistance to acquired adult cerebral dysfunction in all but aphasic or significantly demented individuals." However, our study does not examine "acquired adult cerebral function." Rather, this study examines the effect of repeated head impacts (irrespective of concussions) occurring during a critical neurodevelopmental period in childhood, with the hypothesis that incurring repeated head impacts during this time could result in disrupted brain development and, therefore, a lower adult IQ. That is, the WRAT-4 Reading test, as with most other estimates of overall intelligence, is a measure of the accumulation of learning and development prior to the age of insult(s) as well as the altered trajectory following the insult(s). The age range reflecting the "premorbid" period in studies that use this measure as a covariate is generally equivalent to middle adulthood. In our study, however, "premorbid" would be equivalent to early to mid-childhood (e.g., ages 5-10). Consequently, we strongly feel that it would be inappropriate to use the WRAT-4 reading test as a covariate in this study. Larabee and colleagues provide a brief description of a somewhat unusual re-examination of our findings by using meta-analysis and subtracting the mean of all WCST and NAB List Learning variables from WRAT-4 Reading within each group. Because of the lack of specific information provided for the analysis, it is difficult to determine exactly what was done. However, it appears that their approach would be equivalent to controlling for WRAT-4 Reading in the linear regression model only if the effect of WRAT-4 Reading were equal across outcomes. Although we do not feel that it should have been included in our study for the reasons stated above, we re-ran our regression models for all outcomes while controlling for WRAT-4 Reading by using it as a covariate. We found that the group differences are still significant for NAB-Long Delay T (group difference=7.4, p-value=0.0226) score and WCST % Perservative Errors (group difference=7.3, p-value=0.0333). Despite their statistical significance, we believe that the results of these regressions are meaningless and biased for the reasons we explained. Even if the measure of pre-morbid intelligence is weakly correlated with exposure to head impacts, group differences will be significantly biased. [8] We do agree with Larabee and colleagues that the possible influences of pre- exposure intellectual differences could be elucidated by examining elementary school achievement tests, but these were not available for this study. As stated above and in the publication, an ideal study would observe these measures in a longitudinal design beginning prior to the onset of sport participation.

We view our publication as the first preliminary study of this specific topic and hope that it will encourage future research on this important issue. We are confident in the interpretation of our results, though, as we clearly state, there are many limitations to this initial work. Much more research is needed before rule and policy changes should be made regarding safety in youth sports.

1. Stamm JM, Bourlas AP, Baugh CM, et al. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology 2015;84:1114-1120.

2. Boucherle D. In: Friday Night Tykes: Esquire Network, 2014.

3. Athletes emerge at NextGen [online]. Available at: https://footballrecruiting.rivals.com/content.asp?CID=1736635. Accessed April 9, 2015.

4. Robbins CA, Daneshvar DH, Picano JD, et al. Self-reported concussion history: impact of providing a definition of concussion. Open access journal of sports medicine 2014;5:99-103.

5. McCrea M, Hammeke T, Olsen G, Leo P, Guskiewicz K. Unreported concussion in high school football players: implications for prevention. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine 2004;14:13-17.

6. McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain : a journal of neurology 2013;136:43-64.

7. Kaufman AS, Lichtenberger EO. Assessing adolescent and adult intelligence, 3rd ed. Hoboken, N.J.: Wiley, 2006.

8. Angrist JD, Pischke JS. Mostly Harmless Econometrics: An Empiricist's Companion: Princeton University Press, 2009.

For author disclosures, please contact the editorial office at [email protected].

10 March 2015
Cognitive deficits may predate early entry into football
Glenn J. Larrabee, Neuropsychologist
Martin L. Rohling, Mobile, Alabama; Laurence M. Binder, Beaverton, Oregon

Stamm et al. [1] reported poorer cognitive performance for former professional football players starting play before age 12 (age of first exposure (AFE) less than 12) vs. those starting greater than or equal to 12. One variable, WRAT-4 Reading, is often used to estimate premorbid cognitive ability due to its resistance to acquired adult cerebral dysfunction in all but aphasic or significantly demented individuals. [2] Using meta-analysis, we subtracted the mean of all WCST and NAB List Learning variables from WRAT-4 Reading within each group, and then compared this difference between groups, obtaining a Hedge's g of -.017, p = .956. Thus, group differences appear to be an artifact of premorbid differences in ability rather than showing increased risk of long term deficits secondary to AFE less than 12. Moreover, 3 AFE less than 12 but zero AFE greater than or equal to 12 subjects had learning disability. Since reading disability and phonologic processing problems are typically evident by second grade [3], it is unlikely that WRAT-4 differences represent acquired impairment for AFE less than 12 (mean AFE = 9, fourth grade). Although potentially difficult to obtain, this can be further confirmed by comparing elementary school achievement test scores for the two groups, prior to playing football, which should also show differences. Premorbid impairments often can be misinterpreted as brain injury effects. [4]

1. Stamm JM, Bourlas AP, Baugh CM, et al. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology 2015; ; 0: 0-101212000.

2. Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological assessment, 5th ed. New York: Oxford University Press; 2012.

3. Fletcher JM, Lyon GR, Fuchs LS, Barnes MA. Learning disabilities. From identification to intervention. New York: Guilford; 2007.

4. Larrabee GJ, Binder LM, Rohling ML, Ploetz DM. Meta-analytic methods and the importance of non-TBI factors related to outcome in mild traumatic brain injury: Response to Bigler et al. (2013). Clin Neuropsychol 2013; 27: 215-237.

For disclosures, please contact the editorial office at [email protected].

26 February 2015
Youth football and late-life cognitive impairment
Jim Andrikopoulos, Neuropsychologist
Des Moines, Iowa

This study reports poorer cognitive outcome of National Football players who started playing before versus after the age of 12, noting an astonishing self-reported history of nearly 400 concussions using a "modern" definition in which "seeing stars" qualifies as concussion. [1] Would a neurologist actually record this number of concussions in a patient medical record? Without explanation, the authors report having a noncontact sport control group but chose not to include it. Their claim that reduced intelligence has been reported following concussion in children is inaccurate based on the references cited (references 4-6 in [1]). Intelligence generally refers to IQ and achievement tests. Reference 4 found an attention deficit in those self-reporting concussions. Reference 5 is a review of brain injury with demonstrable lesions, including moderate to severe head injury. Reference 6 refers to severe head injury. None conclude an intellectual decline following concussion. While litigation is mentioned, the authors did not fulfill their obligation outlined in neuropsychology practice guidelines to formally assess for malingering [2, 3]. In view of these significant problems, the decision to issue a press release on this study three days before the Super Bowl unnecessarily alarmed a public already misinformed about the consequences of concussion.

1. Stamm JM, Bourlas AP, Baugh CM, et al. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology 2015;84:xxx-xxx.

2. Heilbronner, RL, Sweet, JJ, Morgan, JE, Larrabee, GJ, & Millis, S. American Academy of Clinical Neuropsychology Consensus Conference Statement on the neuropsychological assessment of effort, response bias, and malingering. The Clinical Neuropsychologist 2009; 23;1093-1129.

3. Bush, SS, Ruff, RM, Troster, AI., Barth, JT., Koffler, SP, Pliskin, NH, Silver, CH. (2005). Symptom validity assessment: Practice issues and medical necessity NAN Policy & Planning Committee. Archives of Clinical Neuropsychology 2005;20:419-426.

For disclosures, please contact the editorial office at [email protected].

23 February 2015
Rebuttal to "Age of first exposure to football and later-life cognitive impairment in former NFL players"
Joseph C. Maroon, Neurosurgeon
Julian Bailes, Pittsburgh, PA; Michael Collins, Pittsburgh, PA; Mark Lovell, Pittsburgh, PA; Christina Mathyssek, Pittsburgh, PA

The study by Stamm et al. may contain some methodological limitations. [1] The small sample was not representative of the general youth football player because most youth players do not go on to play professional football. In addition, the way football was played by the study subjects in the 1960's to '80's is not representative of the improved, safer practices of modern-day youth football programs.

Second, the authors need to more clearly outline their assessment of important variables such as normal score ranges of the outcome variables and choice of group age cut-off of 12 years and its relevance to the outcome variables.

Most importantly, the retrospective research design and lack of proper control variables may explain group differences aside from "early head impact". Parenting style (as to age of football participation) and socioeconomic factors could also explain group differences. Furthermore, these factors can interact with the type and likelihood of post head-impact care, such as health care access or parents who encourage kids to "toughen up" versus "rest", amplifying alternative explanations of group differences. Other limitations include the use of a sub-optimal neuropsychological battery (WRAT) and no proper determination of actual football incurred head impacts exclusive of other sports played.

Stamm et al. acknowledged some limitations but still concluded that "incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment." [1] We believe that their message is not warranted based on their research and overstates the scope of the research performed.

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 84Number 11March 17, 2015
Pages: 1114-1120
PubMed: 25632088

Publication History

Received: September 5, 2014
Accepted: November 12, 2014
Published online: January 28, 2015
Published in print: March 17, 2015

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Disclosure

J. Stamm is funded by NIH Grant F31 NS 081957. A. Bourlas, C. Baugh, N. Fritts, D. Daneshvar, B. Martin, M. McClean, and Y. Tripodis report no disclosures relevant to the manuscript. R. Stern is funded by NIH grants R01 NS078337, R01 CA129769, P30 AG13846, U01 AG10483, and U01 AG015477; and has received research support from Sports Legacy Institute, the Alzheimer's Association, the National Operating Committee on Standards for Athletic Equipment, Avid Radiopharmaceuticals, Eli Lilly, Eisai Pharmaceuticals, Janssen Alzheimer's Immunotherapy, Pfizer, and Medivation. He is a paid consultant to Athena Diagnostics and serves as an expert advisor to attorneys for cases pertaining to the long-term consequences of repetitive brain trauma. He receives royalties from Psychological Assessment Resources for the publication of neuropsychological tests. Go to Neurology.org for full disclosures.

Study Funding

Supported by NIH (R01 NS 078337; F31 NS 081957; P30 AG13846; UL1-TR000157), and participant travel funded by gifts from JetBlue Airlines, the National Football League (NFL), and the NFL Players Association.

Authors

Affiliations & Disclosures

Julie M. Stamm, BS
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
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NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
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NONE
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NONE
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NONE
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NIH, F31NS081957, PI, 2013-2016
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Alexandra P. Bourlas, MA
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
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1.
NONE
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1.
NONE
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1.
NONE
License Fee Payments, Technology or Inventions:
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NONE
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1.
NONE
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NONE
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Christine M. Baugh, MPH
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
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1.
NONE
Research Support, Government Entities:
1.
NIMH, T32MH019733 (PI: Tom McGuire), trainee, 9/2014-present
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1.
Edmond J. Safra Center for Ethics, Harvard University.
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1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Nathan G. Fritts, BA
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Daniel H. Daneshvar, MA
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Brett M. Martin, MS
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Michael D. McClean, ScD
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
1 - Gavin Law Firm, case focused on head and neck cancer, 2012-13 2 - Gavin Law Firm, case focused on exposure to battery acid, 2013
Yorghos Tripodis, PhD
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1) NIA, P30-AG13846, Biostatistician, 2011-2016 2) NIH, R01 ND078337, Biostatistician, 2011, 2015
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Robert A. Stern, PhD
From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
(1) Mackey-White Traumatic Brain Injury Committee, National Football League Players Association (2) Eli Lilly Expert Advisor (3) Medical Advisory Board, Sports Legacy Institute (4) Medical/Scientific Advisory Board, MA/NH Alzheimer's Association (5) Medical Advisory Board, National Graves Disease Foundation
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Congressional Brain Injury Task Force, honorarium, (2) Institute of Medicine Committee on Nutrition, Trauma and the Brain, honorarium, (3) 2010 Head Trauma and the Athlete CME Conference, honorarium, (4) Braintree Neurorehabilitation Conference, honorarium, (5) MassALFA, honorarium, (6) Massachusetts Neurologic Association and the Massachusetts Medical Society, honorarium, (7) American Neuropsychiatric Association, honorarium, (8) American Neuropsychiatric Association, honorarium, (9) The Neuroscience Institute at the University of Tennessee Health Science Center, honorarium, (10) Alzheimer?s Association, honorarium, (11) American Psychological Association, honorarium, (12) Baptist Hospital Annual Brain Injury Symposium, honorarium, (13) National Public Radio, honorarium, (14) Boston Society of Neurology and Psychiatry, honorarium, (15) Boston Surgical Society, honorarium, (16) Vista Health System, honorarium, (17) Alzheimer?s Partnership, honorarium, (18) Shiley-Marcos Alzheimer?s Disease Research Center University of California San Diego, honorarium, (18) Sunnybrook Hospital, honorarium, (19) Brain Injury Association, honorarium, (20) American Psychological Association, honorarium, (21) Chronic Traumatic Encephalopathy (CTE) Conference, honorarium, (22) Society for Neuroscience, honorarium, (23) Boston University School of Medicine, honorarium, (24) New Hampshire Alzheimer?s Association, honorarium, (25) Massachusetts Chapter of the American College of Surgeons, honorarium, (26) National Institutes of Health, honorarium, (27) Traumatic Brain Injury Conference, honorarium, (28) American Health Care Journalists, honorarium, (29) Rose? Webinar Series, honorarium, (30) International Sports Concussion Symposium, honorarium, (31) World Brain Mapping Conference, honorarium, (32) Harvard Medical School, honorarium, (33) The German Center for Research and Innovation and Ludwig-Maximilians-Universit?t M?nchen, honorarium, (34) New York Academy of Sciences, honorarium, (35) Academy of Clinical Neuropsychology, honorarium.
Editorial Boards:
1.
(1) Journal of Neuropsychiatry and Clinical Neurosciences, Associate Editor, 1998-Present, (2) Archives of Clinical Neuropsychology, Member of Editorial Board, 2008-Present, (3) Frontiers in Neurotrauma, Review Editor, 2010-Present, (4) Frontiers in Sports Neurology, Review Editor, 2011- Present, (5) Alzheimer's Research and Therapy, Series Editor, 2012-Present
Patents:
1.
NONE
Publishing Royalties:
1.
(1) Visual Analog Mood Scales, Psychological Assessment Resources, Inc., 1997-Present, (2) Boston Qualitative Scoring System for the Rey-Osterreith Complex Figure, Psychological Assessment Resources, Inc., 1999-Present, (3) Neuropsychological Assessment Resources, Inc., 2003-Present
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Neuronix, (2) Eli Lilly, (3)Janssen Alzheimer's Immunotherapy; Athena Diagnostics
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Janssen Alzheimer's Immunotherapy (previously Elan), (2) Medivation, (3) Pfizer Pharmaceuticals, (4) Eisai Pharmaceuticals, (5)Ely Lilly, (6) Avid Radiopharmaceuticals
Research Support, Government Entities:
1.
(1) NIH, R01NS078337, PI, 2011-2014, (2) NIH, P30-AG13846, Clinical Core Director, 2004-2016, (3) NIH, D01-HP08796, Neuropsychology Director, 2010-2015 (4) NIH, R01-CA129769, PI, 2009-2014, (5)NIH, R01-MH080295, PI, 2008-2014, (6)NIH, U01-AG10483, Site PI, 2007-2012, (7)NIH, R56NS078337, PI, 2014-2015
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Alzheimer's Association
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Stern: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Ms. Stamm is the primary author. She was responsible for drafting the manuscript and interpretation of the data and participated in data acquisition and analysis. Ms. Bourlas participated in data acquisition and drafting and revising the manuscript. Ms. Baugh participated in revising the manuscript, acquisition of data, and study design. Mr. Fritts participated in drafting the manuscript and acquisition of data. Mr. Daneshvar participated in revising the manuscript and study design. Mr. Martin participated in data management and analysis for this study. Dr. McClean participated in revising the manuscript and interpreting the data. Dr. Tripodis conducted the statistical analysis and participated in interpretation of the data. Dr. Stern is the principal and corresponding author. He was responsible for study concept and design, revising the manuscript, and analysis and interpretation of data. He also played a role in obtaining funding.

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