Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers.

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. Data included 237 males (45-74 years) from DIAGNOSE CTE Research Project, including former professional and college football players (COL) ( = 173) and asymptomatic men without RHI or TBI ( = 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. Former professional players had higher d-CIIV than controls (F(7, 194) = 2.87,  = .007). d-CIIV was associated with TES diagnosis (F(8, 146) = 9.063,  < .001), with highest d-CIIV in TES Possible/Probable-CTE. Higher d-CIIV correlated with higher CHII scores ( = 0.19), reduced CSF Aβ ( = -0.302), increased p-tau (= 0.374), and reduced DTI FA ( = -0.202). d-CIIV is linked to RHI exposure and TES diagnosis in former football players, with associated changes in CSF biomarkers and white matter integrity.