Giuseppe Bellelli, Ovidio Brignoli, Marco Canevelli, Antonio Cherubini, Andrew Clegg, Bruno Dubois, Maria Cristina Ferrara, Laura Fratiglioni, Giovanni B Frisoni, Giulia Grande, Frank Jessen, Sean P Kennelly, Alberto Magni, Martina Marelli, Alessandra Marengoni, Nicolás Martínez Velilla, Susan D Shenkin, Marc Suárez-Calvet, Suzanne Timmons, Alessandro Padovani
The introduction of disease-modifying therapies for Alzheimer's disease (AD-DMTs) is reshaping clinical practice, raising critical questions about patient selection, diagnostic pathways, treatment appropriateness, and equity of access. Frailty, a multidimensional condition of reduced physiological reserve and increased vulnerability to stressors, is common in older adults with AD, yet has not been systematically assessed in AD-DMTs trials, limiting the generalizability of trial findings to real-world populations. In this review, we examine the role of frailty in the emerging era of AD-DMTs, summarizing evidence on its prevalence and prognostic relevance, approaches to its assessment, and its potential impact on treatment safety and effectiveness. We propose that regular frailty assessment should inform decision-making in both clinical trials and clinical practice, while frailty-informed management-including medication review and multidomain interventions-may support more appropriate, individualized care.