Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes

OPEN Citation: Transl Psychiatry (2017) 7, e1236; doi:10.1038/tp.2017.197 www.nature.com/tp ORIGINAL ARTICLE Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes ML Alosco1,2, AB Kasimis1, JM Stamm1,3, AS Chua4, CM Baugh1,2,5, DH Daneshvar1, CA Robbins1,6, M Mariani1, J Hayden1, S Conneely1, R Au2,7,8,9, A Torres10,11, MD McClean12, AC McKee1,2,13,14,15, RC Cantu1,2,6,16,17, J Mez1,2, CJ Nowinski1,6, BM Martin1,18, CE Chaisson1,18, Y Tripodis1,4,19 and RA Stern1,2,9,16,19 Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into o 12 and ⩾ 12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with 42 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19–3.91; MI, 2.10,1.17–3.76; CES-D, 3.08,1.65–5.76; AES, 2.39,1.32–4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76–0.97) and CES-D (OR, 95% CI: 0.85, 0.74–0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions. Translational Psychiatry (2017) 7, e1236; doi:10.1038/tp.2017.197; published online 19 September 2017 INTRODUCTION Exposure to repetitive head impacts (RHI) during American football has become a significant concern to clinicians, researchers and the general community because of their association with long-term neurological consequences.1 RHI exposure, with or without symptomatic concussions, can alter the structure and function of the brain to potentially underpin cognitive, behavior and mood deficits observed in some former amateur and professional football players.1–22 An additional growing concern is chronic traumatic encephalopathy (CTE). CTE is a neurodegenerative disease that can only be diagnosed postmortem23 and has been found in individuals exposed to RHI, particularly former American football players and boxers.24–26 Long-term clinical and neurological consequences related to RHI exposure (including those in CTE), however, are quite heterogeneous and have not been observed in all former American football players.25–29 It is hypothesized that RHI exposure interacts with other risk factors (for example,, genetic and environmental) to alter vulnerability to long-term neurological dysfunction. Age of first exposure (AFE) to football may be one modifier of later-life neurological and clinical outcomes. Youth football is played between ages of 5 and 14, a period when the brain undergoes substantial maturation in males.30–42 Exposure to RHI over a single season of youth football (without diagnosed concussions) has been associated with white matter alterations in 8–13 year olds.43 RHI exposure during peak neurodevelopment may disrupt normal brain maturation to increase vulnerability to long-term clinical impairments, especially in the context of continued football participation.44,45 In a study of former National Football League (NFL) players, subjects who began playing football before age 12 exhibited greater verbal memory and executive dysfunction,44 and reduced microstructural integrity of the anterior corpus callosum45 in middle age, compared with those who began playing football at 12 or older. These findings were not replicated in a recent NFL-funded study that examined 1 Boston University Alzheimer’s Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; 2Department of Neurology, Boston University School of Medicine, Boston, MA, USA; 3Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, USA; 4Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; 5Interfaculty Initiative in Health Policy, Harvard University, Boston, MA, USA; 6Concussion Legacy Foundation, Boston, MA, USA; 7Boston University School of Medicine, Boston, MA, USA; 8Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 9Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA; 10Pediatric Neurology, Boston University School of Medicine, Boston, MA, USA; 11Pediatric Neurology, Boston Medical Center, Boston, MA, USA; 12Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA; 13VA Boston Healthcare System, U.S. Department of Veteran Affairs, Boston, MA, USA; 14Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA; 15Department of Veterans Affairs Medical Center, Bedford, MA, USA; 16Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA; 17Department of Neurosurgery, Emerson Hospital, Concord, MA, USA and 18Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA. Correspondence: Dr RA Stern, Boston University Alzheimer’s Disease and CTE Center, Boston University School of Medicine, 72 East Concord Street, B7800, Boston, MA 02118, USA. E-mail: 19 These authors contributed equally to this work. Received 19 April 2017; revised 16 June 2017; accepted 30 July 2017 Age of exposure to football and clinical function ML Alosco et al 2 years of youth football play and clinical outcomes in a sample of 45 former NFL players.46 The few studies that have reported on AFE to football and longterm clinical function are limited by small sample size, inclusion of only former professional football players and lack of assessment of neuropsychiatric features, including behavioral and mood functioning—clinical domains affected by RHI exposure and CTE.27,47,48 Here, we examined the relationship between AFE to football and behavior, mood and cognitive outcomes in a large cohort of both amateur (that is, those who (...truncated)