Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease

Abstract The recent approval of anti-amyloid pharmaceuticals for the treatment of Alzheimer’s disease (AD) has created a pressing need for the ability to accurately identify optimal candidates for anti-amyloid therapy, specifically those with evidence for incipient cognitive decline, since patients...

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Main Authors: Jarrad Perron, Carly Scramstad, Ji Hyun Ko
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02039-2
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author Jarrad Perron
Carly Scramstad
Ji Hyun Ko
author_facet Jarrad Perron
Carly Scramstad
Ji Hyun Ko
author_sort Jarrad Perron
collection DOAJ
description Abstract The recent approval of anti-amyloid pharmaceuticals for the treatment of Alzheimer’s disease (AD) has created a pressing need for the ability to accurately identify optimal candidates for anti-amyloid therapy, specifically those with evidence for incipient cognitive decline, since patients with mild cognitive impairment (MCI) may remain stable for several years even with positive AD biomarkers. Using fluorodeoxyglucose PET and biomarker data from 594 ADNI patients, a neural network ensemble was trained to forecast cognition from MCI diagnostic baseline. Training data comprised PET studies of patients with biological AD. The ensemble discriminated between progressive and stable prodromal subjects (MCI with positive amyloid and tau) at baseline with 88.6% area-under-curve, 88.6% (39/44) accuracy, 73.7% (14/19) sensitivity and 100% (25/25) specificity in the test set. It also correctly classified all other test subjects (healthy or AD continuum subjects across the cognitive spectrum) with 86.4% accuracy (206/239), 77.4% sensitivity (33/42) and 88.23% (165/197) specificity. By identifying patients with prodromal AD who will not progress to dementia, our model could significantly reduce overall societal burden and cost if implemented as a screening tool. The model’s high positive predictive value in the prodromal test set makes it a practical means for selecting candidates for anti-amyloid therapy and trials.
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spelling doaj-art-c8f235551b7d46cdb9109f64dffa8bf62025-08-20T01:51:38ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-02039-2Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s diseaseJarrad Perron0Carly Scramstad1Ji Hyun Ko2Graduate Program in Biomedical Engineering, Price Faculty of Engineering, University of ManitobaSection of Neurology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of ManitobaGraduate Program in Biomedical Engineering, Price Faculty of Engineering, University of ManitobaAbstract The recent approval of anti-amyloid pharmaceuticals for the treatment of Alzheimer’s disease (AD) has created a pressing need for the ability to accurately identify optimal candidates for anti-amyloid therapy, specifically those with evidence for incipient cognitive decline, since patients with mild cognitive impairment (MCI) may remain stable for several years even with positive AD biomarkers. Using fluorodeoxyglucose PET and biomarker data from 594 ADNI patients, a neural network ensemble was trained to forecast cognition from MCI diagnostic baseline. Training data comprised PET studies of patients with biological AD. The ensemble discriminated between progressive and stable prodromal subjects (MCI with positive amyloid and tau) at baseline with 88.6% area-under-curve, 88.6% (39/44) accuracy, 73.7% (14/19) sensitivity and 100% (25/25) specificity in the test set. It also correctly classified all other test subjects (healthy or AD continuum subjects across the cognitive spectrum) with 86.4% accuracy (206/239), 77.4% sensitivity (33/42) and 88.23% (165/197) specificity. By identifying patients with prodromal AD who will not progress to dementia, our model could significantly reduce overall societal burden and cost if implemented as a screening tool. The model’s high positive predictive value in the prodromal test set makes it a practical means for selecting candidates for anti-amyloid therapy and trials.https://doi.org/10.1038/s41598-025-02039-2Deep learningNeuroimagingProdromalFDG PETMCIAlzheimer’s disease
spellingShingle Jarrad Perron
Carly Scramstad
Ji Hyun Ko
Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
Scientific Reports
Deep learning
Neuroimaging
Prodromal
FDG PET
MCI
Alzheimer’s disease
title Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
title_full Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
title_fullStr Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
title_full_unstemmed Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
title_short Brain metabolic imaging-based model identifies cognitive stability in prodromal Alzheimer’s disease
title_sort brain metabolic imaging based model identifies cognitive stability in prodromal alzheimer s disease
topic Deep learning
Neuroimaging
Prodromal
FDG PET
MCI
Alzheimer’s disease
url https://doi.org/10.1038/s41598-025-02039-2
work_keys_str_mv AT jarradperron brainmetabolicimagingbasedmodelidentifiescognitivestabilityinprodromalalzheimersdisease
AT carlyscramstad brainmetabolicimagingbasedmodelidentifiescognitivestabilityinprodromalalzheimersdisease
AT jihyunko brainmetabolicimagingbasedmodelidentifiescognitivestabilityinprodromalalzheimersdisease