OBJECTIVE: To quantify brain health using a measure of reserve that incorporates pre-existing pathology. METHODS: We analyzed 2 retrospective ischemic stroke cohorts (GASROS and SALVO) with neuroimaging and 90-day modified Rankin Scores (mRS) available. White matter hyperintensity (WMHv), brain, and intracranial volumes were automatically extracted and brain parenchymal fraction (BPF) calculated. The latent variable effective reserve (eR) was modeled using age, WMHv, and BPF or brain volume in GASROS. Models were compared using Bayes Information Criterion (BIC). The best model's eR estimates were categorized into quartiles and evaluated in SALVO. RESULTS: GASROS included 476 (median age: 65.8
65.3% male) and SALVO included 43 (median age: 69.2
62.8% male) patients. Inverse associations between eR and mRS was seen in both models, with brain volume outperforming BPF (path coefficients: -0.67, -0.48, respectively
DISCUSSION: Expanding the concept of eR, highlights its clinical translational potential. The strong link between higher eR and better outcomes underscores its value as a protective brain health metric.