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4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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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. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. 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Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
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- 05 August 2015
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- 27 April 2015, pp ix-xxx
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- By Giustino Albanese, Andrew Amaranto, Brandon H. Backlund, Alexander Baxter, Abraham Berger, Mark Bernstein, Marian E. Betz, Omar Bholat, Suzanne Bigelow, Carl Bonnett, Elizabeth Borock, Christopher B. Colwell, Alasdair Conn, Moira Davenport, David Dreitlein, Aaron Eberhardt, Ugo A. Ezenkwele, Diana Felton, Spiros G. Frangos, John E. Frank, Jonathan S. Gates, Lewis Goldfrank, Pinchas Halpern, Jean Hammel, Kristin E. Harkin, Jason S. Haukoos, E. Parker Hays, Aaron Hexdall, James F. Holmes, Debra Houry, Jennifer Isenhour, Andy Jagoda, John L. Kendall, Erica Kreisman, Nancy Kwon, Eric Legome, Matthew R. Levine, Phillip D. Levy, Charles Little, Marion Machado, Heather Mahoney, Vincent J. Markovchick, Nancy Martin, John Marx, Julie Mayglothling, Ron Medzon, Maurizio A. Miglietta, Elizabeth L. Mitchell, Ernest Moore, Maria E. Moreira, Sassan Naderi, Salvatore Pardo, Sajan Patel, David Peak, Christine Preblick, Niels K. Rathlev, Charles Ray, Phillip L. Rice, Carlo L. Rosen, Peter Rosen, Livia Santiago-Rosado, Tamara A. Scerpella, David Schwartz, Fred Severyn, Kaushal Shah, Lee W. Shockley, Mari Siegel, Matthew Simons, Michael Stern, D. Matthew Sullivan, Carrie D. Tibbles, Knox H. Todd, Shawn Ulrich, Neil Waldman, Kurt Whitaker, Stephen J. Wolf, Daniel Zlogar
- Edited by Eric Legome, Lee W. Shockley
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- Trauma
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- 07 September 2011
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- 16 June 2011, pp ix-xiv
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- By Harold P. Adams, Colum F. Amory, Anne Angelillo-Scherrer, Irena Anselm, Marcel Arnold, Robert W. Baloh, Ralf W. Baumgartner, José Biller, Valérie Biousse, Matthias Bischof, Julien Bogousslavsky, Natan M. Bornstein, Marie Germaine Bousser, Robin L. Brey, John C. M. Brust, Alan Bryer, Olivier Calvetti, Louis R. Caplan, José Castillo, Hugues Chabriat, Chin-Sang Chung, Charlotte Cordonnier, Steven C. Cramer, Luís Cunha, Rima M. Dafer, John F. Dashe, Cyrus K. Dastur, Antonio Dávalos, Larry E. Davis, Patricia Davis, Stephen M. Davis, Jan L. De Bleecker, Michael A. De Georgia, Amir R. Dehdashti, Oscar H. Del Brutto, Jacques L. De Reuck, Hans-Christoph Diener, Kathleen B. Digre, Vivian U. Fritz, Nancy Futrell, Bhuwan P. Garg, Philip B. Gorelick, Glenn D. Graham, Alexander Y. Gur, John J. Halperin, Michael Hennerici, Isabel Lestro Henriques, Roberto C. Heros, Daniel B. Hier, Lorenz Hirt, Joanna C. Jen, Taro Kaibara, Sumit Kapoor, Sarosh M. Katrak, Siddharth Kharkar, Walter J. Koroshetz, Monisha Kumar, Sandeep Kumar, Emre Kumral, Tobias Kurth, Rogelio Leira, Steven R. Levine, Didier Leys, Doris Lin, Jonathan Lipton, Alfredo M. Lopez-Yunez, Betsy B. Love, Ayrton Roberto Massaro, Heinrich P. Mattle, Manu Mehdiratta, John H. Menkes, Philippe Metellus, Reto Meuli, Patrik Michel, Panayiotis Mitsias, Jorge Moncayo-Gaete, Julien Morier, Krassen Nedeltchev, Bernhard Neundörfer, Olukemi A. Olugemo, Nikolaos I. H. Papamitsakis, Stephen D. Reck, Luca Regli, Marc D. Reichhart, Daniele Rigamonti, Michael J. Rivkin, E. Steve Roach, Jose F. Roldan, David Z. Rose, Daniel M. Rosenbaum, N. Paul Rosman, Elayna O. Rubens, Sean I. Savitz, Marc Schapira, Robert J. Schwartzman, Magdy Selim, Yukito Shinohara, Aneesh B. Singhal, Michael A. Sloan, Barney J. Stern, Mathias Sturzenegger, Oriana Thompson, A. Wesley Thevathasan, Jonathan D. Trobe, Michael Varner, Dana Védy, Jorge Vidaurre, Engin Y. Yilmaz, Khaled Zamel, Mathieu Zuber
- Edited by Louis R. Caplan, Julien Bogousslavsky
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- Uncommon Causes of Stroke
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- 06 January 2010
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- 09 October 2008, pp ix-xiv
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Community education for cardiovascular health
- from Section 4 - Health practices and the modification of health risk behaviour
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- By J. W. Farquhar, Stanford University, N. MacCoby, Stanford University, P. D. Wood, Stanford University, J. K. Alexander, Stanford University, H. Breitrose, Stanford University, B. W. Brown, Stanford University, W. L. Haskell, Stanford University, A. L. McAlister, Stanford University, A. J. Meyer, Stanford University, J. D. Nash, Stanford University, M. P. Stern, Stanford University
- Edited by Andrew Steptoe, St George's Hospital Medical School, University of London, Jane Wardle, Imperial Cancer Research Fund, London
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- Psychosocial Processes and Health
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- 24 November 1994, pp 316-324
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Summary
Summary
To determine whether community health education can reduce the risk of cardiovascular disease, a field experiment was conducted in three northern California towns. In two of these communities there were extensive mass-media campaigns over a 2-year period, and in one of these, face-to-face counselling was also provided for a small subset of high-risk people. The third community served as a control. People from each community were interviewed and examined before the campaigns began and one and two years afterwards to assess knowledge and behaviour related to cardiovascular disease (e.g., diet and smoking) and also to measure physiological indicators of risk (e.g., blood-pressure, relative weight, and plasma-cholesterol). In the control community the risk of cardiovascular disease increased over the two years but in the treatment communities there was a substantial and sustained decrease in risk. In the community in which there was some face-to-face counselling the initial improvement was greater and health education was more successful in reducing cigarette smoking, but at the end of the second year the decrease in risk was similar in both treatment communities. These results strongly suggest that mass-media educational campaigns directed at entire communities may be very effective in reducing the risk of cardiovascular disease.
Introduction
Cigarette smoking, high plasma-cholesterol concentrations, and high blood-pressure are important risk factors for premature cardiovascular disease. In 1972 we began a field experiment in three northern California communities to attempt to modify these risk factors by community education.
The mass media, face-to-face instruction, or combinations of the two may be used in community education campaigns. The habits influencing cardiovascular risk factors are complex and longstanding ones, are often reinforced by culture, custom, and continual commercial advertising, and are unlikely to be strongly influenced by mass media alone. Face-to face instruction and exhortation also have a long history of failure, particularly when aimed at producing permanent changes in diet and smoking habits. The disappointing results of a very limited attempt to reduce cardiovascular risk with a direct mail and lecture campaign reinforced pessimism about the possibility of changing health behaviour through public education.
After considering the powerful cultural forces which reinforce and maintain the health habits that we wished to change, and in view of the failure of past health education campaigns, we decided to use an untested combination of an extensive mass-media campaign plus a considerable amount of face-to-face instruction.
The Neutrino Concept
- Alexander W. Stern
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- Journal:
- Philosophy of Science / Volume 8 / Issue 4 / October 1941
- Published online by Cambridge University Press:
- 14 March 2022, pp. 614-617
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- October 1941
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Quantum mechanics was initiated with the object of allowing only observable concepts to enter into the theory. The new mechanics has, however, inherited the old difficulty with the conservation laws involved in beta decay, and this led Pauli, about 1931, to introduce the idea of the neutrino, with the object of reconciling the facts of beta decay with the conservation laws. The neutrino, as it was proposed by Pauli and as accepted today, is a particle devoid both of mass and charge, but having a spin 1/2 and obeying the Fermi statistics. In 1934 Fermi founded his theory of beta disintegration based on the neutrino. The Fermi theory assumes that this hypothetical particle is emitted simultaneously with the disintegrating electron and carries off the excess energy, thereby reconciling the conservation laws with beta disintegration. It will be remembered that the continuous distribution in energy of the beta particles is such that, except at the maximum energy end point of the beta spectra, there is more energy available from the disintegration than is emitted in the form of beta particles.