Publication date: Jan 26, 2025

Background: Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction. This study examined d-CIIV in former football players and its associations with TES diagnosis, RHI exposure, and DTI and CSF biomarkers. Methods: Data included 237 males (45-74 years) from DIAGNOSE CTE Research Project, including former professional and college football players (COL) (n = 173) and asymptomatic men without RHI or TBI (n = 55). Participants completed neuropsychological tests. TES diagnosis was based on 2021 NINDS TES criteria. Years of football play and a cumulative head impact index (CHII) measured RHI exposure. Lumipulse technology was used for CSF assays. DTI fractional anisotropy assessed white matter integrity. Coefficient of variation (CoV) measured d-CIIV. ANCOVA compared d-CIIV among groups (football versus control; TES-status). Pearson correlations and linear regressions tested associations between d-CIIV, RHI exposure, and CSF and DTI biomarkers. Results: Former professional players had higher d-CIIV than controls (F(7, 194) = 2. 87, p = . 007). d-CIIV was associated with TES diagnosis (F(8, 146) = 9. 063, p

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