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64 Neuroimaging Evidence of Neurodegenerative Disease in Former Professional American Football Players Who “Fail” Validity Testing: A Case Series
- Ranjani Shankar, Julia Culhane, Leonardo Iaccarino, Chris Nowinski, Nidhi Mundada, Karen Smith, Jeremy Tanner, Charles Windon, Yorghos Tripodis, Gustavo Mercier, Thor D Stein, Anne C McKee, Robert A Stern, Neil Kowall, Bruce L Miller, Jesse Mez, Ron Killiany, Gil D Rabinovici, Michael L Alosco, Breton M Asken
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 574-575
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Objective:
Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).
Participants and Methods:Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.
Results:All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).
Conclusions:Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.
Ten new insights in climate science 2020 – a horizon scan
- Erik Pihl, Eva Alfredsson, Magnus Bengtsson, Kathryn J. Bowen, Vanesa Cástan Broto, Kuei Tien Chou, Helen Cleugh, Kristie Ebi, Clea M. Edwards, Eleanor Fisher, Pierre Friedlingstein, Alex Godoy-Faúndez, Mukesh Gupta, Alexandra R. Harrington, Katie Hayes, Bronwyn M. Hayward, Sophie R. Hebden, Thomas Hickmann, Gustaf Hugelius, Tatiana Ilyina, Robert B. Jackson, Trevor F. Keenan, Ria A. Lambino, Sebastian Leuzinger, Mikael Malmaeus, Robert I. McDonald, Celia McMichael, Clark A. Miller, Matteo Muratori, Nidhi Nagabhatla, Harini Nagendra, Cristian Passarello, Josep Penuelas, Julia Pongratz, Johan Rockström, Patricia Romero-Lankao, Joyashree Roy, Adam A. Scaife, Peter Schlosser, Edward Schuur, Michelle Scobie, Steven C. Sherwood, Giles B. Sioen, Jakob Skovgaard, Edgardo A. Sobenes Obregon, Sebastian Sonntag, Joachim H. Spangenberg, Otto Spijkers, Leena Srivastava, Detlef B. Stammer, Pedro H. C. Torres, Merritt R. Turetsky, Anna M. Ukkola, Detlef P. van Vuuren, Christina Voigt, Chadia Wannous, Mark D. Zelinka
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- Journal:
- Global Sustainability / Volume 4 / 2021
- Published online by Cambridge University Press:
- 27 January 2021, e5
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Non-technical summary
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
Technical summaryA synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
Social media summaryStronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE)
- C. Norman Coleman, Judith L. Bader, John F. Koerner, Chad Hrdina, Kenneth D. Cliffer, John L. Hick, James J. James, Monique K. Mansoura, Alicia A. Livinski, Scott V. Nystrom, Andrea DiCarlo-Cohen, Maria Julia Marinissen, Lynne Wathen, Jessica M. Appler, Brooke Buddemeier, Rocco Casagrande, Derek Estes, Patrick Byrne, Edward M. Kennedy, Ann A. Jakubowski, Cullen Case, Jr, David M. Weinstock, Nicholas Dainiak, Dan Hanfling, Andrew L. Garrett, Natalie N. Grant, Daniel Dodgen, Irwin Redlener, Thomas F. MacKAY, Meghan Treber, Mary J. Homer, Tammy P. Taylor, Aubrey Miller, George Korch, Richard Hatchett
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 13 / Issue 5-6 / December 2019
- Published online by Cambridge University Press:
- 17 June 2019, pp. 995-1010
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A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Contributors
- Edited by Ben Eggleston, University of Kansas, Dale E. Miller, Old Dominion University, Virginia
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- Book:
- The Cambridge Companion to Utilitarianism
- Published online:
- 05 February 2014
- Print publication:
- 30 January 2014, pp ix-xii
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Contributors
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- By Nalini Vadivelu, Christian J. Whitney, Raymond S. Sinatra, M. Khurram Ghori, Yu-Fan (Robert) Zhang, Raymond S. Sinatra, Joshua Wellington, Yuan-Yi Chia, Francis J. Keefe, Jon McCormack, Ian Power, John Butterworth, P. M. Lavand’homme, M. F. De Kock, Bradley Urie, Oscar A. de Leon-Casasola, Frederick M. Perkins, Larry F. Chu, David Clark, Martin S. Angst, Cynthia M. Welchek, Lisa Mastrangelo, Raymond S. Sinatra, Richard Martinez, Scott S. Reuben, Asokumar Buvanendran, Raymond S. Sinatra, Pamela E Macintyre, Julia Coldrey, Daniel B. Maalouf, Spencer S. Liu, Susan Dabu-Bondoc, Samantha A. Franco, Raymond S. Sinatra, James Benonis, Jennifer Fortney, David Hardman, Gavin Martin, Holly Evans, Karen C. Nielsen, Marcy S. Tucker, Stephen M. Klein, Benjamin Sherman, Ikay Enu, Raymond S. Sinatra, James W. Heitz, Eugene R. Viscusi, Jonathan S. Jahr, Kofi N. Donkor, Raymond S. Sinatra, Manzo Suzuki, Johan Raeder, Vegard Dahl, Stefan Erceg, Keun Sam Chung, Kok-Yuen Ho, Tong J. Gan, Dermot R. Fitzgibbon, Paul Willoughby, Brian E. Harrington, Joseph Marino, Tariq M. Malik, Raymond S. Sinatra, Giorgio Ivani, Valeria Mossetti, Simona Italiano, Thomas M. Halaszynski, Nousheh Saidi, Javier Lopez, Kate Miller, Ferne Braveman, Jaya L. Varadarajan, Steven J. Weisman, Sukanya Mitra, Raymond S. Sinatra, Theodore J. Saclarides, Knox H. Todd, James R. Miner, Chris Pasero, Nancy Eksterowicz, Margo McCaffery, Leslie N. Schechter, Amr E. Abouleish, Govindaraj Ranganathan, Tee Yong Tan, Stephan A. Schug, Marie N. Hanna, Spencer S. Liu, Christopher L. Wu, Craig T. Hartrick, Garen Manvelian, Christine Miaskowski, Brian Durkin, Peter S. A. Glass
- Edited by Raymond S. Sinatra, Oscar A. de Leon-Cassasola, University of Rochester Medical Center, New York, Eugene R. Viscusi, Brian Ginsberg
- Foreword by Henry McQuay
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- Book:
- Acute Pain Management
- Published online:
- 26 October 2009
- Print publication:
- 27 April 2009, pp vii-xii
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Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms
- Stephen M. Lawrie, Heather C. Whalley, Suheib S. Abukmeil, Julia N. Kestelman, Patrick Miller, Jonathan J. K. Best, David G. C. Owens, Eve C. Johnstone
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- Journal:
- The British Journal of Psychiatry / Volume 181 / Issue 2 / August 2002
- Published online by Cambridge University Press:
- 02 January 2018, pp. 138-143
- Print publication:
- August 2002
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Background
Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. These are thought to be neurodevelopmental in origin, but when they become evident is unknown.
AimsTo determine iftemporal lobe volumes reduce during the development of symptoms of schizophrenia in initially well people at high riskofthis disorder.
MethodA group of 66 people who had at least two first— or second-degree relatives with schizophrenia and a control group of 20 healthy people had a structural MRI scan ofthe whole brain which was repeated after approximately 2 years. Regions of interest, specifically the amygdala-hippocampus complex and the temporal lobes, were traced semi-automatically by three masked raters with good inter— and intrarater reliability
ResultsRegional brain volume changes over 2 years did notdiffer between high-risk and healthy participants. Within the high-risk group, the 19 people with psychotic symptoms (12 at first assessment) had a mean reduction of 2163 mm3 intherighttemporal lobe compared with 97 mm3 in the 47 without symptoms (P⩵0.02).
ConclusionsOur findings suggest that people at high risk of schizophrenia with psychotic symptoms show reductions in temporal lobe volumes.
Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
- Published online by Cambridge University Press:
- 23 October 2020, pp. 1986-2078
- Print publication:
- December 2000
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Evolution of Classic Period Architecture in the Eastern Acropolis, Copan: A progress report
- Robert J. Sharer, Julia C. Miller, Loa P. Traxler
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- Journal:
- Ancient Mesoamerica / Volume 3 / Issue 1 / Spring 1992
- Published online by Cambridge University Press:
- 18 October 2010, pp. 145-159
- Print publication:
- Spring 1992
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Interpreting the social meaning of polity center architecture opens a window onto the organization and history of the society responsible for its construction. Our research is designed to examine the form, function, and organization of Copan's Acropolis architecture. Through a unique program of tunneling, surface excavation, and architectural recording, more than 400 years of monumental architecture (c. A.D. 400–800) are being documented and analyzed to comprehend the evolution of the Acropolis and its role in the Copan polity. The dramatic erosion cut through the eastern Acropolis edge allows ready access to all major construction levels and presents a rare opportunity for extensive exposure of superimposed architectural plans. Our tunneling excavation methods provide a more complete, less destructive, and more efficient means of such documentation. Exposed architecture is being recorded by a computer-assisted mapping program, its first application to the sequential development of Classic Maya architecture, and its first use in tunnel excavations. As a result, our research is documenting the architectural transformation of the Acropolis during the time of Copan's increasing sociopolitical complexity and is doing so at a level of detail impossible to achieve by most projects using traditional archaeological techniques. The correspondence between architectural data and data sets from epigraphy, iconography, and settlement survey is being evaluated in light of current discussion on the political and economic trajectory of Copan in particular, and in general, the architectural expression of political power and integration in complex societies.