Integrating frailty into decision-making for disease-modifying therapies in Alzheimer’s disease: a proposed expert-opinion based approach

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.

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Publication Details

Journal
The Journal of Prevention of Alzheimer s Disease
Published
2026-09-04
DOI
https://doi.org/10.1016/j.tjpad.2026.100666
Primary Topic
Frailty in Older Adults
Type
article
Field-Weighted Citation Impact
0.00

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article

Integrating frailty into decision-making for disease-modifying therapies in Alzheimer’s disease: a proposed expert-opinion based approach

MC Ferrara, GB Frisoni, B Dubois, SD Shenkin et al.
The Journal of Prevention of Alzheimer s Disease
Frailty in Older Adults
article

Integrating frailty into decision-making for disease-modifying therapies in Alzheimer’s disease: a proposed expert-opinion based approach

MC Ferrara, GB Frisoni, B Dubois, SD Shenkin, A Clegg, N Martínez Velilla, F Jessen, A Magni, M Suárez-Calvet, G Grande, G Bellelli, O Brignoli, L Fratiglioni, A Padovani, S Timmons, M Canevelli, SP Kennelly, A Marengoni, A Cherubini, M Marelli
article en

Abstract

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.

The Journal of Prevention of Alzheimer s DiseaseVol. 13(9)
Marche Polytechnic University (IT), University of Bradford (GB), Inserm (FR), Stockholm University (SE), Trinity College Dublin (IE), University College Cork (IE), Karolinska Institutet (SE), Sorbonne Université (FR), Klinik und Poliklinik für Psychosomatik und Psychotherapie (DE), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Pasqual Maragall Foundation (ES), Navarre Institute of Health Research (ES), Navarrabiomed (ES), Società Italiana di Medicina Generale (IT), Klinik und Poliklinik für Psychiatrie und Psychotherapie (DE), Institut du Cerveau (FR), Istituto Nazionale di Riposo e Cura per Anziani (IT), Geneva College (US), University of Milano-Bicocca (IT), University of Brescia (IT), University of Edinburgh (GB)
Università degli Studi di Milano
Peace, Justice and strong institutions
Openalex Percentile: Top 16%
Frailty in Older Adults
DOIOpen Access PDFOpenAlex
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