Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-14T19:47:46.794Z Has data issue: false hasContentIssue false

64 Neuroimaging Evidence of Neurodegenerative Disease in Former Professional American Football Players Who “Fail” Validity Testing: A Case Series

Published online by Cambridge University Press:  21 December 2023

Ranjani Shankar*
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Julia Culhane
Affiliation:
Boston University, Boston, MA, USA.
Leonardo Iaccarino
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Chris Nowinski
Affiliation:
Boston University, Boston, MA, USA.
Nidhi Mundada
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Karen Smith
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Jeremy Tanner
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Charles Windon
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Yorghos Tripodis
Affiliation:
Boston University, Boston, MA, USA.
Gustavo Mercier
Affiliation:
Boston Medical Center, Boston, MA, USA.
Thor D Stein
Affiliation:
Boston University, Boston, MA, USA.
Anne C McKee
Affiliation:
Boston University, Boston, MA, USA.
Robert A Stern
Affiliation:
Boston University, Boston, MA, USA.
Neil Kowall
Affiliation:
Boston University, Boston, MA, USA.
Bruce L Miller
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Jesse Mez
Affiliation:
Boston University, Boston, MA, USA.
Ron Killiany
Affiliation:
Boston University, Boston, MA, USA.
Gil D Rabinovici
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA.
Michael L Alosco
Affiliation:
Boston University, Boston, MA, USA.
Breton M Asken
Affiliation:
UCSF Memory and Aging Center, San Francisco, CA, USA. University of Florida, Gainesville, FL, USA
*
Correspondence: Ranjani Shankar, UCSF Memory and Aging Center, Department of Neurology, ranjani.shankar@ucsf.edu
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
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.

Type
Poster Session 01: Medical | Neurological Disorders | Neuropsychiatry | Psychopharmacology
Copyright
Copyright © INS. Published by Cambridge University Press, 2023