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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.
Discourses of climate delay
- William F. Lamb, Giulio Mattioli, Sebastian Levi, J. Timmons Roberts, Stuart Capstick, Felix Creutzig, Jan C. Minx, Finn Müller-Hansen, Trevor Culhane, Julia K. Steinberger
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- Journal:
- Global Sustainability / Volume 3 / 2020
- Published online by Cambridge University Press:
- 01 July 2020, e17
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‘Discourses of climate delay’ pervade current debates on climate action. These discourses accept the existence of climate change, but justify inaction or inadequate efforts. In contemporary discussions on what actions should be taken, by whom and how fast, proponents of climate delay would argue for minimal action or action taken by others. They focus attention on the negative social effects of climate policies and raise doubt that mitigation is possible. Here, we outline the common features of climate delay discourses and provide a guide to identifying them.