Abstract
Background: Anti-amyloid therapies (AAT) are reshaping the therapeutic landscape of Alzheimer’s disease (AD), yet their implementation remains constrained by the risk of amyloid-related imaging abnormalities (ARIA). Although the ARIA phenomenon is well recognized, most available evidence stems from clinical trial safety reports framed predominantly from a dementia-oriented perspective, with relatively limited integration of vascular neurology principles. Methods: In this narrative review, we examine drug-induced ARIA through a neurovascular lens, highlighting how cerebrovascular comorbidity, particularly cerebral amyloid angiopathy (CAA), influences the risk and severity of ARIA. Results: We critically evaluated how CAA comorbidity has been assessed in randomized controlled trials, focusing on exclusion criteria, imaging thresholds, and the resulting implications for external validity. Finally, we evaluated current approaches to ARIA risk stratification and proposed a more integrative framework that combines vascular imaging markers, APOE ε4 genotype, and key clinical comorbidities. Conclusions: A more tailored patient selection and monitoring strategies may ultimately improve real-world outcomes and optimize resources in the era of AAT.