Quantifying and Examining Reserve in Symptomatic Former National Football League Players

Article type: Research Article

Authors: Foley, Éimear M.^{a; b; c} | Tripodis, Yorghos^{a; d} | Yhang, Eukyung^d | Koerte, Inga K.^{e; f} | Martin, Brett M.^{a; g} | Palmisano, Joseph^{a; g} | Makris, Nikos^{e; h; j} | Schultz, Vivian^{e; f; k} | Lepage, Chris^l | Muehlmann, Marc^m | Wróbel, Paweł P.^{e; f; n} | Guenette, Jeffrey P.^{e; h} | Cantu, Robert C.^{a; o; p; q} | Lin, Alexander P.^r | Coleman, Michael^e | Mez, Jesse^{a; s} | Bouix, Sylvain^{e; h} | Shenton, Martha E.^{e; h} | Stern, Robert A.^{a; i; p} | Alosco, Michael L.^{a; *}

Affiliations: [a] Boston University Alzheimer’s Disease Research Center and Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [b] Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands | [c] Department of Psychiatry, University of Cambridge, Cambridge, UK | [d] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [e] Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [f] cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany | [g] Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, MA, USA | [h] Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [i] Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [j] Department of Psychiatry, Center for Morphometric Analysis, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [k] Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany | [l] QEII Health Sciences Centre, Nova Scotia, Canada | [m] Department of Radiology, Ludwig-Maximilian-University, Munich, Germany | [n] Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany | [o] Concussion Legacy Foundation, Boston, MA, USA | [p] Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA | [q] Department of Neurosurgery, Emerson Hospital, Concord, MA, USA | [r] Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [s] Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Michael L. Alosco, PhD, Boston University Alzheimer’s Disease Research Center and Boston University CTE Center, Department of Neurology, Boston University School of Medicine, 72 E. Concord Street, Suite B7800, Boston, MA 02118, USA. Tel.: +1 617 358 6029; E-mail: [email protected].

Abstract: Background:Repetitive head impacts (RHI) from contact sports have been associated with cognitive and neuropsychiatric disorders. However, not all individuals exposed to RHI develop such disorders. This may be explained by the reserve hypothesis. It remains unclear if the reserve hypothesis accounts for the heterogenous symptom presentation in RHI-exposed individuals. Moreover, optimal measurement of reserve in this population is unclear and likely unique from non-athlete populations. Objective:We examined the association between metrics of reserve and cognitive and neuropsychiatric functioning in 89 symptomatic former National Football League players. Methods:Individual-level proxies (e.g., education) defined reserve. We additionally quantified reserve as remaining residual variance in 1) episodic memory and 2) executive functioning performance, after accounting for demographics and brain pathology. Associations between reserve metrics and cognitive and neuropsychiatric functioning were examined. Results:Higher reading ability was associated with better attention/information processing (β=0.25; 95% CI, 0.05–0.46), episodic memory (β=0.27; 95% CI, 0.06–0.48), semantic and phonemic fluency (β=0.24; 95% CI, 0.02–0.46; β=0.38; 95% CI, 0.17–0.59), and behavioral regulation (β=–0.26; 95% CI, –0.48, –0.03) performance. There were no effects for other individual-level proxies. Residual episodic memory variance was associated with better attention/information processing (β=0.45; 95% CI, 0.25, 0.65), executive functioning (β=0.36; 95% CI, 0.15, 0.57), and semantic fluency (β=0.38; 95% CI, 0.17, 0.59) performance. Residual executive functioning variance was associated with better attention/information processing (β=0.44; 95% CI, 0.24, 0.64) and episodic memory (β=0.37; 95% CI, 0.16, 0.58) performance. Conclusion:Traditional reserve proxies (e.g., years of education, occupational attainment) have limitations and may be unsuitable for use in elite athlete samples. Alternative approaches of reserve quantification may prove more suitable for this population.

Keywords: Chronic traumatic encephalopathy, cognition, cognitive reserve, football, neurodegenerative diseases, repetitive head impacts, resilience

DOI: 10.3233/JAD-210379

Journal: Journal of Alzheimer's Disease, vol. 85, no. 2, pp. 675-689, 2022