Improving the clinical trial landscape for patients with atypical variants of Alzheimer's disease

Authors

• Nick Corriveau-Lecavalier, Mayo Clinic Rochester
• Neus Falgàs, Hospital Clinic de Barcelona-IDIBAPS and CIBEREHDFollow
• Deepti Putcha, Harvard University
• Jonathan Graff-Radford, Mayo Clinic Rochester
• Keir X.X. Yong, University College London
• Baayla D.C. Boon, Mayo Clinic College of Medicine and Science
• Rosaleena Mohanty, Karolinska Institutet
• Eric Westman, Karolinska Institutet
• Colin Groot, Vrije Universiteit Amsterdam
• David T. Jones, Mayo Clinic Rochester
• Lea T. Grinberg, Mayo Clinic College of Medicine and Science
• Gil D. Rabinovici, University of California San Francisco
• Jennifer L. Whitwell, Mayo Clinic Rochester
• Liana G. Apostolova, Indiana University School of Medicine
• Melissa E. Murray, Mayo Clinic College of Medicine and Science
• Dustin B. Hammers, Indiana University School of Medicine
• Suzanne E. Schindler, Washington University School of Medicine in St. Louis
• Inga Atonsdottir, Johns Hopkins University
• Elizabeth K. Rhodus, University of KentuckyFollow
• Jonathan M. Schott, University College London
• Ignacio Illán-Gala, CIBER - Center for Biomedical Research Network
• Ogbuagu Chukwuanugo, Nnamdi Azikiwe University, Awka
• Jorge J.Llibre Guerra, Washington University School of Medicine in St. Louis
• Ruth Peters, University of New South Wales
• Erin L. Abner, University of KentuckyFollow
• Carla Abdelnour, Stanford University
• Albert Lladó, Hospital Clinic de Barcelona-IDIBAPS and CIBEREHD
• Renaud La Joie, University of California San Francisco

Abstract

Patients with atypical variants of Alzheimer's disease (AD) often present at a younger age with predominantly non-amnestic impairments and a more aggressive disease course. Historically, individuals with atypical presentations have not been included in large-scale clinical trials, which typically focus on late-onset, sporadic amnestic-predominant AD. Consequently, treatment options and research efforts specific to atypical AD remain limited. The emergence of amyloid-targeting therapies that slow disease progression underscores these challenges, as evidence supporting their efficacy in early-onset amnestic and non-amnestic AD variants is scarce. This perspective article argues that atypical AD represents an excellent disease model for clinical trials and proposes strategies to address critical gaps in clinical trial design for this population. Key considerations include optimizing participant selection approaches, establishing syndrome-specific or surrogate biological and clinical endpoints, and fostering advocacy to enhance early and accurate diagnosis, equitable representation, and outcomes for these populations.

Document Type

Article

Publication Date

6-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Digital Object Identifier (DOI)

10.1002/alz.71521

Archival?

Archival

Repository Citation

Corriveau-Lecavalier, Nick; Falgàs, Neus; Putcha, Deepti; Graff-Radford, Jonathan; Yong, Keir X.X.; Boon, Baayla D.C.; Mohanty, Rosaleena; Westman, Eric; Groot, Colin; Jones, David T.; Grinberg, Lea T.; Rabinovici, Gil D.; Whitwell, Jennifer L.; Apostolova, Liana G.; Murray, Melissa E.; Hammers, Dustin B.; Schindler, Suzanne E.; Atonsdottir, Inga; Rhodus, Elizabeth K.; Schott, Jonathan M.; Illán-Gala, Ignacio; Chukwuanugo, Ogbuagu; Guerra, Jorge J.Llibre; Peters, Ruth; Abner, Erin L.; Abdelnour, Carla; Lladó, Albert; and La Joie, Renaud, "Improving the clinical trial landscape for patients with atypical variants of Alzheimer's disease" (2026). Epidemiology and Environmental Health Faculty Publications. 109.
https://uknowledge.uky.edu/epidemiology_facpub/109