Background: Structural brain changes, potentially resulting from repetitive brain trauma (RBT), have been correlated with neurocognitive decline and increased symptom reporting in retired athletes.Hypothesis: In a cohort of retired National Football League (NFL) players, the relationships between 3 neuroimaging parameters, neuropsychological testing, and symptom scores will be significantly correlated.Study Design: Cross-sectional study.Level Of Evidence: Level 3.Methods: Comprehensive magnetic resonance imaging was performed in 45 retired NFL players. Three neuroanatomical parameters were assessed by board-certified radiologists blinded to the purpose of the study: (1) the absence or presence of small or large cavum septum pellucidum, (2) a global mean score of fractional anisotropy (FA), and (3) the presence or absence of microhemorrhages. The subjects underwent a battery of 9 paper-and-pencil neuropsychological tests, a computerized neurocognitive test, and multiple symptom and depression scales. The associations among the neuroimaging results with these outcome measures were assessed utilizing Pearson, Spearman rank, and point-biserial correlations.Results: The 45 subjects (mean age, 46.7 ± 9.1 years) reported a mean 6.9 (±6.2) concussions and 13.0 (±7.9) "dings" in the NFL. Ten (22%) did not have a cavum septum pellucidum, while 32 (71%) had a small and 3 (7%) had a large one. Four (9%) had microhemorrhages. Global FA mean was 0.459 (±0.035). The majority (50.8%) of correlations among the neuroimaging parameters and neurocognitive/symptom scores fell below the threshold of "small" effect size ( r < 0.10). The remaining (49.2%) correlations were between "small" and "medium" effect sizes (0.1 < r < 0.3). However, all correlations were statistically nonsignificant.Conclusion: There were minimal and statistically nonsignificant correlations among the neuroimaging, neurocognitive, and symptom scores examined in this cohort of NFL retirees.Clinical Relevance: Associating the severity of structural brain changes to neurocognitive performance and symptom burden after RBT is complex may involve other moderating variables or biomarkers, and demands further study. [ABSTRACT FROM AUTHOR]