2025 American Academy of Neurology Abstract Website

Objective:

To assess whether brain health measured in patients with acute ischemic stroke (AIS) mediates the relationship between acute infarct volume and long-term functional outcome.

Background:

Brain health facilitates resilience to withstand detrimental effects of neurological diseases. Acute infarct volume is associated with poor outcome after AIS, but the potential mediating effects of brain health have not been investigated.

Design/Methods:

We analyzed AIS survivors with available admission MRI from the GASROS (derivation, single center; 2003-2011) and MRI-GENIE (validation, 17 international centers; 2003-2011) cohorts. White matter hyperintensity (WMH) and brain volume were measured on T2-FLAIR, and acute infarct volume on diffusion weighted imaging. We quantified brain health using effective reserve (eR), defined as a latent variable in structural equation modeling based on age, WMH load, and brain volume, with coefficients estimated in the derivation cohort. Mediation analysis was used to evaluate if eR (indirect pathway: infarct volume-eR-functional outcome) mediates the effect of infarct volume on functional outcome (direct pathway: infarct volume-functional outcome, modified Rankin Scale [mRS] at 90 days).

Results:

We included 997 patients with similar distributions of baseline characteristics and outcomes between the derivation (n=454) and validation (n=543) cohorts (reported as median; age 65/68 years, 35/40% female, NIHSS 3/4, acute infarct volume 2.1/4.1cc, 90-day mRS 1/1 for GASROS/MRI-GENIE). In both cohorts, eR significantly mitigated 17% and 12% of the effect of infarct volume on functional outcome (direct effect [95% confidence interval]: ß=0.30 [0.11-0.20, p<0.001] / ß=0.25 [0.10-0.20, p<0.001], indirect effect mediated through eR: ß=-0.05 [-0.04 to -0.01, p=0.001] / ß=-0.04 [-0.04 to -0.004, p=0.022]), in the derivation/validation cohort.

Conclusions:

Brain health, quantified using the biomarker eR, mitigates the detrimental effects of acute infarct volume on functional outcome after AIS. Hence, brain health metrics should be considered while modeling functional outcome after AIS.