2025 American Academy of Neurology Abstract Website

Ryan Conrad¹, Yorghos Tripodis², Charles Adler³, Laura Balcer⁴, Sarah J. Banks⁵, William Barr⁶, Jennifer Wethe³, Nicholas Ashton⁷, Henrik Zetterberg⁷, Kaj Blennow⁷, Elaine Peskind⁸, Robert C. Cantu⁹, David Dodick³, Jesse Mez⁹, Joseph Palmisano², Brett Martin², Jeffrey Cummings¹⁰, Eric Reiman¹¹, Martha Shenton¹², Robert Stern⁹, Michael Alosco¹
¹Boston University, ²School of Public Health, Boston University, ³Mayo Clinic Arizona, ⁴NYU Grossman School of Medicine, ⁵University of California San Diego, ⁶Langone Health Center, New York University, ⁷University of Gothenburg, ⁸University of Washington, ⁹Boston University School of Medicine, ¹⁰University of Nevada, Las Vegas, ¹¹Banner Alzheimer's Institute, ¹²Brigham and Women's Hospital, Harvard Medical School

Objective:

To examine the association between subjective feelings of loneliness and cognitive and neuropsychiatric outcomes in former elite American football players.

Background:

Persistent feelings of loneliness increase risk for Alzheimer’s disease and dementia. Former professional American football players are at risk for chronic traumatic encephalopathy (CTE) and related symptoms, including cognitive impairment and neuropsychiatric changes. This population is associated with a unique social network composition compared to average US males, which may increase their risk for loneliness.

Design/Methods:

Participants included former professional (n=109) and college (n=52) football players, and unexposed asymptomatic men (n=50) from the DIAGNOSE CTE Research Project. Participants were male, with mean (SD) age of 57.7 (8.3), and 34.3% were Black or African American. Participants completed the revised UCLA (rUCLA) loneliness scale. Traumatic encephalopathy syndrome (TES), the clinical syndrome potentially indicative of CTE, was diagnosed via consensus conferences, and levels of CTE certainty (none/suggestive, possible/probable) were assigned. Participants completed objective neuropsychological testing and self-report scales of neuropsychiatric status. Factor analytic methods were used to derive cognitive and neurobehavioral dysregulation factor scores. Cerebrospinal fluid was analyzed for p-tau181 and markers of neuroinflammation/neurodegeneration (IL-6, NfL). Analyses of covariance assessed associations between TES and cognitive/neurobehavioral function on rUCLA, controlling for demographic, social, and cardiovascular risk factors.

Results:

Compared to TES-no, those with TES had higher rUCLA (mean diff=11.1, p<0.001). Loneliness trended higher in players with possible/probable CTE (mean diff=5.5, p=0.057). Among players, loneliness was associated with worse executive functioning (p=0.011), greater symptoms in all factors of neurobehavioral dysregulation (ps<0.001), and higher CSF IL-6 (p=0.009). No associations were found with p-tau181 or NfL. Football players had higher rUCLA than unexposed men who had no cognitive or mood/behavioral symptoms at recruitment.

Conclusions:

Former elite American football players might be at increased risk for loneliness, potentially contributing to and/or resulting from underlying neurological changes.