INS NYC 2024 Program

Poster	Poster Session 03 Program Schedule 02/15/2024 09:30 am - 10:40 am Room: Majestic Complex (Posters 61-120) Poster Session 03: Neurotrauma \| Neurovascular Final Abstract #67 Clinical and Repetitive Head Impact Correlates of 18F-MK-6240 Tau PET in Former National Football League Players Ranjani Shankar, UCSF, San Francisco, United States Jhony Mejia Perez, UCSF, San Francisco, United States Nidhi Mundada, University of Pennsylvania, Philadelphia, United States Renaud La Joie, UCSF, San Francisco, United States Daniel Schonhaut, UCSF, San Francsico, United States Breton Asken, University of Florida, Gainesville, United States Chris Nowinski, Concussion Legacy Foundation, Boston, United States Karen Smith, UCSF, San Francisco, United States Julia Culhane, Fordham University, Bronx, United States Alinda Amuiri, UCSF, San Francisco, United States Leonardo Iaccarino, UCSF, San Francisco, United States Charles Windon, UCSF, San Francisco, United States Yorghos Tripodis, Boston University, Boston, United States Gustavo Mercier, Boston University, Boston, United States Thor Stein, Boston University, Boston, United States Lea Grinberg, UCSF, San Francisco, United States Ann McKee, Boston University, Boston, United States Robert Stern, Boston University, Boston, United States Bruce Miller, UCSF, San Francisco, United States Jesse Mez, Boston University, Boston, United States Gil Rabinovici, UCSF, San Francisco, United States Michael Alosco, Boston University, Boston, United States Category: Neuroimaging Keyword 1: positron emission tomography Keyword 2: sports-related neuropsychology Objective: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is caused, in part, by exposure to repetitive head impacts (RHIs). At this time, CTE can only be diagnosed at autopsy using published neuropathological diagnostic criteria. ¹⁸F-MK-6240, a second-generation tau radiotracer, has promise to detect the tau deposits of CTE. In this preliminary study, we examined the association between MK-6240 tau PET uptake with proxies of RHI exposure and neuropsychological test performance in former National Football League (NFL) players. Participants and Methods: The sample included 29 former NFL players who had subjective cognitive symptoms (ages 45 to 78, median = 60, 41.4% Black). Participants completed neuropsychological testing, and tau (MK-6240) and amyloid (Florbetapir) PET scans. Years of football play and age of first exposure to football were self-reported and served as proxies of RHI exposure and CTE risk. Neuropsychological tests that assessed effort (Test of Memory Malingering; TOMM) episodic memory (Craft Story 21 Delay Recall, NAB List Learning Long Delay), semantic fluency (Animal Fluency), and executive functioning (Trails B) were analyzed. Seventy-to-ninety-minute MK-6240 standardized uptake value ratio (SUVR) images were created using cerebellar gray matter reference. Based on the neuropathology of CTE, frontal, temporal, and medial temporal lobe (MTL) regions of interest (ROIs) were examined. Partial correlations tested associations between MK-6240 ROI SUVRs with (1) proxies of RHI and (2) neuropsychological raw scores. Analyses controlled for age, and clinical measure analyses also controlled for education. Due to the small sample size, emphasis is placed on effect sizes and p<0.10 were considered meaningful. Results: Of the 29 former NFL players, consensus clinical diagnoses were clinically normal (N=9), mild cognitive impairment (N=15), and dementia (N=5). All amyloid PET scans were visually read as negative. Years of football played was not significantly correlated with SUVRs of any ROIs (r=-0.23 to r=0.02). Controlling for total years of football play, younger age of first exposure to football correlated with higher SUVRs for the dorsolateral prefrontal (r=-0.41, p=0.03) and superior frontal cortex (r=-0.40, p=0.04). This effect was attenuated when age was included (r=-0.28, r=-0.27, respectively). For clinical measure comparisons, 4 participants who failed effort testing (TOMM Trial 2 < 45) were excluded. Regarding memory test performance, higher parahippocampal gyrus SUVRs were associated with lower Craft Story 21 Delayed Recall paraphrase (r=-0.40, p=0.06) and verbatim scores (r=-0.38, p=0.08). There were no associations for NAB List Long Delay (p>0.10). Lower Animal fluency scores correlated with higher SUVRs in the inferior frontal gyrus (r=-0.47, p=0.03), ventromedial prefrontal (r=-0.48, p=0.02), lateral temporal (r=-0.43, p=0.05), and superior temporal (r=-0.42, p=0.05) regions, and they were also associated with higher dorsolateral prefrontal cortex SUVR (r=-0.38, p=0.08). There were no associations with Trails B. Conclusions: There were modest and inconsistent correlations between regional MK-6240 tracer retention on PET and American football exposure and neuropsychological tests of episodic memory and semantic fluency. The usefulness of MK-6240 tau PET in people at risk for CTE remains unclear and warrants additional investigation in larger sample sizes.

Poster

02/15/2024
09:30 am - 10:40 am
Room: Majestic Complex (Posters 61-120)

Poster Session 03: Neurotrauma | Neurovascular

Final Abstract #67

Clinical and Repetitive Head Impact Correlates of 18F-MK-6240 Tau PET in Former National Football League Players

Ranjani Shankar, UCSF, San Francisco, United States
Jhony Mejia Perez, UCSF, San Francisco, United States
Nidhi Mundada, University of Pennsylvania, Philadelphia, United States
Renaud La Joie, UCSF, San Francisco, United States
Daniel Schonhaut, UCSF, San Francsico, United States
Breton Asken, University of Florida, Gainesville, United States
Chris Nowinski, Concussion Legacy Foundation, Boston, United States
Karen Smith, UCSF, San Francisco, United States
Julia Culhane, Fordham University, Bronx, United States
Alinda Amuiri, UCSF, San Francisco, United States
Leonardo Iaccarino, UCSF, San Francisco, United States
Charles Windon, UCSF, San Francisco, United States
Yorghos Tripodis, Boston University, Boston, United States
Gustavo Mercier, Boston University, Boston, United States
Thor Stein, Boston University, Boston, United States
Lea Grinberg, UCSF, San Francisco, United States
Ann McKee, Boston University, Boston, United States
Robert Stern, Boston University, Boston, United States
Bruce Miller, UCSF, San Francisco, United States
Jesse Mez, Boston University, Boston, United States
Gil Rabinovici, UCSF, San Francisco, United States
Michael Alosco, Boston University, Boston, United States

Category: Neuroimaging

Keyword 1: positron emission tomography
Keyword 2: sports-related neuropsychology

Objective:

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is caused, in part, by exposure to repetitive head impacts (RHIs). At this time, CTE can only be diagnosed at autopsy using published neuropathological diagnostic criteria. ¹⁸F-MK-6240, a second-generation tau radiotracer, has promise to detect the tau deposits of CTE. In this preliminary study, we examined the association between MK-6240 tau PET uptake with proxies of RHI exposure and neuropsychological test performance in former National Football League (NFL) players.

Participants and Methods:

The sample included 29 former NFL players who had subjective cognitive symptoms (ages 45 to 78, median = 60, 41.4% Black). Participants completed neuropsychological testing, and tau (MK-6240) and amyloid (Florbetapir) PET scans. Years of football play and age of first exposure to football were self-reported and served as proxies of RHI exposure and CTE risk. Neuropsychological tests that assessed effort (Test of Memory Malingering; TOMM) episodic memory (Craft Story 21 Delay Recall, NAB List Learning Long Delay), semantic fluency (Animal Fluency), and executive functioning (Trails B) were analyzed. Seventy-to-ninety-minute MK-6240 standardized uptake value ratio (SUVR) images were created using cerebellar gray matter reference. Based on the neuropathology of CTE, frontal, temporal, and medial temporal lobe (MTL) regions of interest (ROIs) were examined. Partial correlations tested associations between MK-6240 ROI SUVRs with (1) proxies of RHI and (2) neuropsychological raw scores. Analyses controlled for age, and clinical measure analyses also controlled for education. Due to the small sample size, emphasis is placed on effect sizes and p<0.10 were considered meaningful.

Results:

Of the 29 former NFL players, consensus clinical diagnoses were clinically normal (N=9), mild cognitive impairment (N=15), and dementia (N=5). All amyloid PET scans were visually read as negative. Years of football played was not significantly correlated with SUVRs of any ROIs (r=-0.23 to r=0.02). Controlling for total years of football play, younger age of first exposure to football correlated with higher SUVRs for the dorsolateral prefrontal (r=-0.41, p=0.03) and superior frontal cortex (r=-0.40, p=0.04). This effect was attenuated when age was included (r=-0.28, r=-0.27, respectively). For clinical measure comparisons, 4 participants who failed effort testing (TOMM Trial 2 < 45) were excluded. Regarding memory test performance, higher parahippocampal gyrus SUVRs were associated with lower Craft Story 21 Delayed Recall paraphrase (r=-0.40, p=0.06) and verbatim scores (r=-0.38, p=0.08). There were no associations for NAB List Long Delay (p>0.10). Lower Animal fluency scores correlated with higher SUVRs in the inferior frontal gyrus (r=-0.47, p=0.03), ventromedial prefrontal (r=-0.48, p=0.02), lateral temporal (r=-0.43, p=0.05), and superior temporal (r=-0.42, p=0.05) regions, and they were also associated with higher dorsolateral prefrontal cortex SUVR (r=-0.38, p=0.08). There were no associations with Trails B.

Conclusions:

There were modest and inconsistent correlations between regional MK-6240 tracer retention on PET and American football exposure and neuropsychological tests of episodic memory and semantic fluency. The usefulness of MK-6240 tau PET in people at risk for CTE remains unclear and warrants additional investigation in larger sample sizes.