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% CI 0.2% to 5.0%; p=0.034). The Risk Ratio was 1.96 (95% CI 1.04 to 3.70). Kaplan-Meier 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% CI 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.