Continuous amyloid staging complements global amyloid burden in early Alzheimer's disease
- 1Indiana University Indianapolis
Abstract
Introduction: Early Alzheimer's disease (AD) staging remains challenging because clinical categories and global amyloid PET measures provide only coarse characterization of disease progression. We developed a continuous amyloid staging score from regional amyloid PET to complement global amyloid burden. Methods: Using longitudinal florbetapir PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we trained an end-to-end deep learning model to directly estimate a continuous amyloid staging score. We evaluated longitudinal consistency, its relationship with global amyloid burden, regional contributors to early-stage variation, and whether the staging score stratified subsequent memory decline among participants matched for baseline global amyloid burden. Cognitive analyses were replicated in A4+LEARN. Results: The staging score better preserved longitudinal visit order than existing amyloid staging approaches. During early disease stages, it captured regional amyloid variation despite relatively stable global amyloid burden. Among participants with similar baseline global amyloid burden, higher staging scores were associated with faster subsequent memory decline in both ADNI and A4+LEARN. Discussion: A continuous amyloid staging score complements global amyloid burden for early AD staging and cognitive risk stratification. Keywords: Alzheimer's disease; amyloid PET; disease staging; cognitive decline
Related
- Skull Bone Marrow as a Cranial Neuroimmune Reservoir in Alzheimer’s Disease: Amyloid, Osteoimmune Remodeling, and Translational Imaging Evidence
- Butyrate Regulates the Blood–Brain Barrier Transport and Intraendothelial Accumulation of Alzheimer’s Disease Amyloid-Beta Peptides
- Imipramine binds to amyloid-β and extends the survival of Alzheimer's disease patients
- Amyloid PET Quantitation and Centiloid Thresholds in the Diagnosis of Alzheimer Disease
- Divergent amyloid trajectories distinguish normal aging from Alzheimer's disease progression
BibTeX
@misc{liu2026continuous,
title = {{Continuous amyloid staging complements global amyloid burden in early Alzheimer's disease}},
author = {H. Liu and M. Tong and S. Fang and E. C. Mormino and R. A. Sperling and P. Aisen and R. Buckley and P. Crane and T. J. Hohman and A. J. Saykin and J. Yan and For the Alzheimers Disease Neuroimaging Initiative},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.03.756367},
url = {https://www.biorxiv.org/content/10.64898/2026.10.03.756367v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Continuous amyloid staging complements global amyloid burden in early Alzheimer's disease
AU - H. Liu
AU - M. Tong
AU - S. Fang
AU - E. C. Mormino
AU - R. A. Sperling
AU - P. Aisen
AU - R. Buckley
AU - P. Crane
AU - T. J. Hohman
AU - A. J. Saykin
AU - J. Yan
AU - For the Alzheimers Disease Neuroimaging Initiative
PY - 2026
DA - 2026/10/03
PB - bioRxiv
DO - 10.64898/2026.10.03.756367
UR - https://www.biorxiv.org/content/10.64898/2026.10.03.756367v1
AB - Introduction: Early Alzheimer's disease (AD) staging remains challenging because clinical categories and global amyloid PET measures provide only coarse characterization of disease progression. We developed a continuous amyloid staging score from regional amyloid PET to complement global amyloid burden. Methods: Using longitudinal florbetapir PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we trained an end-to-end deep learning model to directly estimate a continuous amyloid staging score. We evaluated longitudinal consistency, its relationship with global amyloid burden, regional contributors to early-stage variation, and whether the staging score stratified subsequent memory decline among participants matched for baseline global amyloid burden. Cognitive analyses were replicated in A4+LEARN. Results: The staging score better preserved longitudinal visit order than existing amyloid staging approaches. During early disease stages, it captured regional amyloid variation despite relatively stable global amyloid burden. Among participants with similar baseline global amyloid burden, higher staging scores were associated with faster subsequent memory decline in both ADNI and A4+LEARN. Discussion: A continuous amyloid staging score complements global amyloid burden for early AD staging and cognitive risk stratification. Keywords: Alzheimer's disease; amyloid PET; disease staging; cognitive decline
ER -