Neurology. 2026 Sep 22;107(6):e218475. doi: 10.1212/WNL.0000000000218475. Epub 2026 Aug 28.
ABSTRACT
BACKGROUND AND OBJECTIVES: Former American football players exposed to repetitive head impacts (RHI) are at a risk of chronic traumatic encephalopathy (CTE), but chronic pain, polypharmacy, and extensive orthopedic surgeries may also contribute to cognitive and behavioral symptoms. This study evaluated associations between chronic pain, centrally acting medications (CAMs), and orthopedic surgeries with cognitive and behavioral symptoms among former American football players.
METHODS: The sample included former professional (PRO) and collegiate (COL) football players and unexposed, asymptomatic men (UE) from DIAGNOSE CTE. Number of CAMs, orthopedic surgeries, and average pain scores were compared between the groups. Among former football players, logistic regression tested associations between CAMs, average pain score, and orthopedic surgeries with diagnoses of cognitive impairment and neurobehavioral dysregulation (NBD) using traumatic encephalopathy syndrome (TES) research criteria. Linear regression tested associations between CAMs, average pain score, and orthopedic surgeries with the Montreal Cognitive Assessment (MoCA) and behavioral and mood symptom scales. Covariates included age, education, race, and total years of football.
RESULTS: The study included 236 men (120 PRO, 60 COL, 56 UE). The mean ages were 59.1 (PRO), 53.5 (COL) and 59.6 (UE) years. PRO and COL used more CAMs (mean PRO = 0.76, COL = 1.14, UE = 0.14), had higher average pain scores (PRO = 4.22, COL = 3.21, UE = 1.05), and more orthopedic surgeries than the UE (mean PRO = 2.76, COL = 1.22, UE = 0.34). CAMs and average pain scores were associated with increased odds of consensus diagnosed NBD (CAMs OR = 2.15, 95% CI 1.53 to 3.26; average pain score OR = 1.55, 95% CI 1.32 to 1.85). CAMs and average pain scores were associated with increased measures of impulsivity, depression, anxiety, behavioral regulation, and aggression. CAMs and average pain scores were not associated with consensus diagnosed cognitive impairment, but CAMs were negatively associated with MoCA score (estimate = -0.47, 95% CI -0.81 to -0.13). There was no association between number of orthopedic surgeries and cognition or NBD.
DISCUSSION: CAMs and chronic pain are associated with NBD and CAMs are associated with reduced MoCA scores in former American football players.
PMID:42664488 | DOI:10.1212/WNL.0000000000218475
