Full-compartmental modeling of [18F]FDG PET suggests divergent brain metabolism trajectories from healthy aging to early Alzheimer disease
4 affiliations
- 1Department of Information Engineering, University of Padova, Padua, Italy
- 2Neuroimaging Laboratories Research Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO USA
- 3Knight ADRC, Department of Neurology, Washington University School of Medicine, St. Louis, USA
- 4Padova Neuroscience Center, University of Padova, Padova, Italy
Abstract
Within the Alzheimer disease (AD) spectrum, metabolic alterations occur in addition to proteinopathies. While hypometabolism is frequently observed in the late symptomatic stages, characterizing the metabolic changes during early AD stages might aid in both understanding its pathophysiology and in patient selection for future treatments. In this study, we conduct an exploratory, data-driven analysis aimed at better understanding the timing and specificity of the metabolic changes in early AD. Using kinetic analysis of [18F]FDG PET brain imaging data coming from 223 individuals, including 33 preclinical individuals and 19 symptomatic individuals, we find new evidence of a more complex spatiotemporal trajectory of glucose metabolism in early AD, which includes a paradoxical regional increase in glucose phosphorylation during preclinical AD. These findings suggest that the pathologic phases of AD parallel changes in brain glucose metabolism, which is readily assessable with [18F]FDG PET imaging. Moreover, they may indicate that metabolic interventions may work differently during preclinical AD as compared to the early symptomatic phase.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-64573-x.
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BibTeX
@article{francisci2026fullcompartmental,
title = {{Full-compartmental modeling of [18F]FDG PET suggests divergent brain metabolism trajectories from healthy aging to early Alzheimer disease}},
author = {Mattia De Francisci and Edoardo Faggionato and Chiara Dalla Man and John J. Lee and Nicholas Metcalf and Marcus E. Raichle and John C. Morris and Tammie L.S. Benzinger and Andrei G. Vlassenko and Alessandra Bertoldo and Manu S. Goyal},
journal = {Scientific Reports},
year = {2026},
month = aug,
doi = {10.1038/s41598-026-64573-x},
url = {https://doi.org/10.1038/s41598-026-64573-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Full-compartmental modeling of [18F]FDG PET suggests divergent brain metabolism trajectories from healthy aging to early Alzheimer disease
AU - Mattia De Francisci
AU - Edoardo Faggionato
AU - Chiara Dalla Man
AU - John J. Lee
AU - Nicholas Metcalf
AU - Marcus E. Raichle
AU - John C. Morris
AU - Tammie L.S. Benzinger
AU - Andrei G. Vlassenko
AU - Alessandra Bertoldo
AU - Manu S. Goyal
PY - 2026
DA - 2026/08/13
JO - Scientific Reports
DO - 10.1038/s41598-026-64573-x
UR - https://doi.org/10.1038/s41598-026-64573-x
AB - Within the Alzheimer disease (AD) spectrum, metabolic alterations occur in addition to proteinopathies. While hypometabolism is frequently observed in the late symptomatic stages, characterizing the metabolic changes during early AD stages might aid in both understanding its pathophysiology and in patient selection for future treatments. In this study, we conduct an exploratory, data-driven analysis aimed at better understanding the timing and specificity of the metabolic changes in early AD. Using kinetic analysis of [18F]FDG PET brain imaging data coming from 223 individuals, including 33 preclinical individuals and 19 symptomatic individuals, we find new evidence of a more complex spatiotemporal trajectory of glucose metabolism in early AD, which includes a paradoxical regional increase in glucose phosphorylation during preclinical AD. These findings suggest that the pathologic phases of AD parallel changes in brain glucose metabolism, which is readily assessable with [18F]FDG PET imaging. Moreover, they may indicate that metabolic interventions may work differently during preclinical AD as compared to the early symptomatic phase. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-64573-x.
SN - 2045-2322
ER -