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Improving the clinical trial landscape for patients with atypical variants of Alzheimer's disease : a call to action

Corriveau-Lecavalier, Nick ; Falgàs, Neus ; Putcha, Deepti ; Graff-Radford, Jonathan ; Yong, Keir X.X. ; Boon, Baayla D.C. ; Mohanty, Rosaleena ; Westman, Eric ; Groot, Colin LU and Jones, David T. , et al. (2026) In Alzheimer's and Dementia 22(6).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atypical Alzheimer's disease, clinical trials, dementia, heterogeneity
in
Alzheimer's and Dementia
volume
22
issue
6
article number
e71521
publisher
Wiley
external identifiers
  • scopus:105042598335
  • pmid:42334062
ISSN
1552-5260
DOI
10.1002/alz.71521
language
English
LU publication?
yes
id
ea096d78-00da-4f19-8ff2-2ebf5ee6c846
date added to LUP
2026-08-28 12:23:24
date last changed
2026-09-11 13:14:41
@article{ea096d78-00da-4f19-8ff2-2ebf5ee6c846,
  abstract     = {{<p>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.</p>}},
  author       = {{Corriveau-Lecavalier, Nick and Falgàs, Neus and Putcha, Deepti and Graff-Radford, Jonathan and Yong, Keir X.X. and Boon, Baayla D.C. and Mohanty, Rosaleena and Westman, Eric and Groot, Colin and Jones, David T. and Grinberg, Lea T. and Rabinovici, Gil D. and Whitwell, Jennifer L. and Apostolova, Liana G. and Murray, Melissa E. and Hammers, Dustin B. and Schindler, Suzanne E. and Atonsdottir, Inga and Rhodus, Elizabeth K. and Schott, Jonathan M. and Illán-Gala, Ignacio and Chukwuanugo, Ogbuagu and Guerra, Jorge J.Llibre and Peters, Ruth and Abner, Erin L. and Abdelnour, Carla and Lladó, Albert and La Joie, Renaud and de Souza, Leonardo Cruz and Rezaii, Neguine and Shir, Dror and Pijenburg, Yolande A.L. and Carrillo, Maria C. and Dickerson, Bradford C. and Aisen, Paul and Ossenkoppele, Rik and Raman, Rema}},
  issn         = {{1552-5260}},
  keywords     = {{atypical Alzheimer's disease; clinical trials; dementia; heterogeneity}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Improving the clinical trial landscape for patients with atypical variants of Alzheimer's disease : a call to action}},
  url          = {{http://dx.doi.org/10.1002/alz.71521}},
  doi          = {{10.1002/alz.71521}},
  volume       = {{22}},
  year         = {{2026}},
}