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INTEGRATING FRAILTY INTO DECISION-MAKING FOR DISEASE-MODIFYING THERAPIES IN ALZHEIMER’S DISEASE: A PROPOSED EXPERT-OPINION BASED APPROACH

Giuseppe Bellelli, Ovidio Brignoli, Marco Canevelli, Antonio Cherubini, Maria Cristina Ferrara, Laura Fratiglioni, Giovanni B. Frisoni, Giulia Grande, Alberto Magni, Martina Marelli, Alessandra Marengoni, Nicolás Martínez Velilla, 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.

CITATION:
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: Integrating frailty into decision-making for disease-modifying therapies in Alzheimer’s disease: a proposed expert-opinion based approach. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.1016/j.tjpad.2026.100666

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