To determine whether AE patients with OA have an increased risk of Cognitive Impairment compared with Isolated AE patients.

Almost 75% of patients with AE experience Persistent Cognitive Deficits. OA, a marker of Axonal Injury, may help indicate a subgroup that is at a higher risk for Cognitive Impairment, but this relationship needs to be explored.

We used the TriNetX US Collaborative Network (included 67 healthcare organizations) to identify adults aged 18-55 with AE. Two Cohorts were defined: Isolated AE (Cohort 1, n=66,790) and AE with OA (Cohort 2, n=437). Index was the first qualifying AE event, and outcomes were assessed from day 3 post-index to 3 years. Cognitive Outcomes included Mild Cognitive Impairment, and Dementia. Propensity Score Matching (1:1) was performed on Demographics and Baseline Covariates, yielding 425 patients per group. Associations were tested using Risk Measures and Kaplan-Meier Survival Analysis.

After Propensity Score Matching, Baseline Characteristics were balanced between the 425 patients with Isolated AE and the 425 patients with AE and OA (mean age 37 years; 60% female). Over a median follow-up of 2.7 years, Cognitive Outcomes occurred in 25/425 patients (5.9%) with AE and OA versus 14/425 patients (3.3%) with Isolated AE. The Risk Difference was +2.6% (95% Cl 0.2% to 5.0%; p=0.034). The Risk Ratio was 1.96 (95% Cl 1.04 to 3.70). Kaplan-Meie Analysis showed a numerical difference towards lower cognitive event-free survival in patients with OA (90.96% vs. 95.19% at study end, log-rank p=0.095). The Hazard Ratio was 1.72 (95% Cl 0.90 to 3.33; p=0.20).

Our findings suggest that OA may be a marker of neurodegenerative vulnerability in AE, and could serve as a clinical prognostic marker.