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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.
59 Objectively-Measured Performance on Tests of Episodic Memory and Executive Function in Autopsy-Confirmed Chronic Traumatic Encephalopathy
- Madeline Uretsky, Evan Nair, Nicole Saltiel, Bobak Abdolmohammadi, Sydney Mosaheb, Julia Culhane, Brett Martin, Joseph Palmisano, Yorghos Tripodis, Robert Stern, Victor Alvarez, Bertrand Russell Huber, Thor Stein, Ann McKee, Jesse Mez, Michael 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. 264-265
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Objective:
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that can only be diagnosed at post-mortem. Revised criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES), include impairments in episodic memory and/or executive function as core clinical features. These criteria were informed by retrospective interviews with next-of-kin and the presence and rates of objective impairments in memory and executive functions in CTE are unknown. Here, we characterized antemortem neuropsychological test performance in episodic memory and executive functions among deceased contact sport athletes neuropathologically diagnosed with CTE.
Participants and Methods:The sample included 80 deceased male contact sport athletes from the UNITE brain bank who had autopsy-confirmed CTE (and no other neurodegenerative diseases). Published criteria were used for the autopsy diagnosis of CTE. Neuropsychological test reports (raw scores) were acquired through medical record requests. Raw scores were converted to z-scores using the same age, sex, and education-adjusted normative data. Tests of memory included long delay trials from the Rey Complex Figure, CVLT-II, HVLT-R, RBANS, and BVMT-R. Tests of executive functions included Trail Making Test-B (TMT-B), Controlled Oral Word Association Test, WAIS-III Picture Arrangement, and various WAIS-IV subtests. Not all brain donors had the same tests, and the sample sizes vary across tests, with 33 donors having tests from both domains. Twenty-eight had 1 test in memory and 3 had 2+. Eight had 1 test of executive function and 46 had 2+. A z-score of 1.5 standard deviations below the normative mean was impaired. Interpretation of test performance followed the American Academy of Clinical Neuropsychology guidelines (Guilmette et al., 2020). Bivariate correlations assessed cumulative p-tau burden (summary semiquantitative ratings of p-tau severity across 11 brain regions) and TMT-B (n=34) and CVLT-II (n=14), the most common tests available.
Results:Of the 80 (mean age= 59.9, SD=18.0 years; 13, 16.3% were Black), 72 played football, 4 played ice hockey, and 4 played other contact sports. Most played at the professional level (57, 71.3%). Mean time between neuropsychological testing and death was 3.9 (SD= 4.5) years. The most common reason for testing was dementia-related (43, 53.8%). Mean z-scores fell in the average psychometric range(mean z= -0.52, SD=1.5, range= -6.0 to 3.0) for executive function and the low average range for memory (mean z= -1.3, SD=1.1, range= -4.0 to 2.0). Eleven (20.4%) had impairment on 1 test and 3 (5.6%) on 2+ tests of executive functions. The most common impairment was on TMT-B (mean z= -1.77, 13 [38.2%] impaired). For memory, 13 (41.9%) had impairment on 1 test. Of the 14 who had CVLT-II, 7 were impaired (mean z= -1.33). Greater p-tau burden was associated with worse performance on CVLT-II (r= -.653, p= .02), but not TMT-B (r= .187, p>.05).
Conclusions:This study provides the first evidence for objectively-measured impairments in executive functions and memory in a sample with known, autopsy-confirmed CTE. Furthermore, p-tau burden corresponded to worse memory test performance. Examination of neuropsychological tests from medical records has limitations but can overcome shortcomings of retrospective informant reports to provide insight into the cognitive profiles associated with CTE.
No evidence for an association between facial fluctuating asymmetry and vocal attractiveness in men or women
- Tobias L. Kordsmeyer, Yasmin T. K. Thies, Omid Ekrami, Julia Stern, Christoph Schild, Cristina Spoiala, Peter Claes, Stefan Van Dongen, Lars Penke
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- Journal:
- Evolutionary Human Sciences / Volume 2 / 2020
- Published online by Cambridge University Press:
- 29 June 2020, e35
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Facial fluctuating asymmetry (FA), presumably a proxy measure of developmental instability, has been proposed to inversely relate to vocal attractiveness, which may convey information on heritable fitness benefits. Using an improved method of measuring facial FA, we sought to replicate two recent studies that showed an inverse correlation of facial FA with vocal attractiveness. In two samples of men (N = 165) and women (N = 157), we investigated the association of automatically measured facial FA based on 3D face scans with male and female observer-rated attractiveness of voice recordings. No significant associations were found for men or women, also when controlling for facial attractiveness, age, and body mass index. Equivalence tests show that effect sizes were significantly smaller than previous meta-analytic effects, providing robust evidence against a link of facial FA with vocal attractiveness. Thus, our study contradicts earlier findings that vocal attractiveness may signal genetic quality in humans via an association with FA.
Chapter 2 - Mary Chesnut’s Epic Time
- from Part I - Materializing Time
- Edited by Cindy Weinstein, California Institute of Technology
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- Book:
- A Question of Time
- Published online:
- 30 November 2018
- Print publication:
- 13 December 2018, pp 32-47
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17 - Mary Boykin Chesnut: Epic and Miniature
- from Part III - Figures
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- By Julia A. Stern, Northwestern University
- Edited by Coleman Hutchison, University of Texas, Austin
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- Book:
- A History of American Civil War Literature
- Published online:
- 05 December 2015
- Print publication:
- 01 December 2015, pp 257-271
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Summary
In March 1864, Southern intellectual and Civil War saloniste Mary Boykin Chesnut attended a Richmond prisoner exchange, joined by Confederate President Jefferson Davis and exiled Irish nationalist John Mitchel. After Davis addressed the assembled crowd, Chesnut spotted another group of Southern luminaries: “the Lees were all there – stood in a group in full fig [sic] – Custis, Rooney, Robert, Chapman Leigh, Mary Agnes, Mildred. Custis will be gazetted in a few days major general and put in command of Richmond.” The appearance of the general's extensive family, men in uniform, and women passionately dedicated to the Confederate cause rallied Chesnut's spirits. Turning her gaze on the redeemed captives, she found shattered-looking men who appeared “as if they had been dead to this world for years.” The contrast could not have been more striking: Chesnut identified Lee and his soldier sons as quasi-Olympic gods, while across the field, she registered their antitypes, ruined shells dragged back from the underworld. In her revised 1880s account of this seminal 1864 moment, Chesnut had inserted herself into the epic tradition.
Mary Boykin Chesnut drafted and revised the most encyclopedic and searching Civil War narrative in American letters. Yet 130-plus years after she left it unfinished at her death, the book continues to be misunderstood as a primary-source artifact, mistaken for a massive journal rather than acknowledged as a self-conscious work of art cast in diary form. I begin this essay by untangling the complicated textual history of Chesnut's revised narrative. In what was the era of realism, she had deployed a fragmented form that went unrecognized by her first editors, who “smoothed” her prose into traditional paragraphs and pages. Chesnut crafted her revised Civil War epic from thousands of what she called “scraps,” both short and occasionally longer bursts of battlefield reports, home-front observations, anecdotes concerning her elite Confederate social circle, and personal commentary about family members and beloved friends. Recognizing the narrative virtuosity abiding in these smaller and larger shards, distinguished Southern historian Michael O'Brien has gestured toward the idea that Chesnut is a modernist writer avant le lettre.
On the vast frame of the epic, Chesnut built her revised narrative from miniatures. With lapidary care, she set anecdote against observation, dramatic scene beside factual assertion.
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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