Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults

Abstract Although brain amyloid and tau deposition measured by PET scans are established as biomarkers of Alzheimer’s disease (AD), they can emerge decades before symptoms are detectable on traditional neuropsychological (NP) tests. There is a pressing need for early AD detection tools that are more...

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Main Authors: Huitong Ding, Chenglin Lyu, Cody Karjadi, Preeti Sunderaraman, Christina B. Young, Elizabeth C. Mormino, Spencer Low, Sherral Devine, Katherine Gifford, Rhoda Au, Honghuang Lin
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95852-8
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author Huitong Ding
Chenglin Lyu
Cody Karjadi
Preeti Sunderaraman
Christina B. Young
Elizabeth C. Mormino
Spencer Low
Sherral Devine
Katherine Gifford
Rhoda Au
Honghuang Lin
author_facet Huitong Ding
Chenglin Lyu
Cody Karjadi
Preeti Sunderaraman
Christina B. Young
Elizabeth C. Mormino
Spencer Low
Sherral Devine
Katherine Gifford
Rhoda Au
Honghuang Lin
author_sort Huitong Ding
collection DOAJ
description Abstract Although brain amyloid and tau deposition measured by PET scans are established as biomarkers of Alzheimer’s disease (AD), they can emerge decades before symptoms are detectable on traditional neuropsychological (NP) tests. There is a pressing need for early AD detection tools that are more accessible, cost-effective, and non-invasive. The digital clock drawing test (dCDT), a digital version of the clock drawing test, has emerged as a promising cognitive assessment tool that takes minutes to administer and can reveal clinical symptoms earlier than paper–pencil NP tests. This study explored the association between 53 dCDT measures and amyloid and tau PET biomarkers using data from 87 low age risk participants in the Framingham Heart Study. Our findings revealed a significant association between a dCDT measure related to spatial reasoning function and global amyloid burden (P < 0.05), and 4 dCDT measures correlated with tau accumulation after adjusting for multiple comparisons. Notably, the combination of demographic variables and a composite dCDT score achieved a mean area under the receiver operating characteristics curve of 0.86 in detecting amyloid positivity. These results highlight the potential of dCDT measures as effective predictors of amyloid and tau pathology in preclinical AD.
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spelling doaj-art-54733027d13a41ceb0567d4ee2df5efb2025-08-20T03:04:49ZengNature PortfolioScientific Reports2045-23222025-04-011511810.1038/s41598-025-95852-8Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adultsHuitong Ding0Chenglin Lyu1Cody Karjadi2Preeti Sunderaraman3Christina B. Young4Elizabeth C. Mormino5Spencer Low6Sherral Devine7Katherine Gifford8Rhoda Au9Honghuang Lin10Department of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineDepartment of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineDepartment of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineThe Framingham Heart Study, Boston University Chobanian and Avedisian School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of MedicineDepartment of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineDepartment of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineDepartment of Neurology, Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical CenterDepartment of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of MedicineDepartment of Medicine, University of Massachusetts Chan Medical SchoolAbstract Although brain amyloid and tau deposition measured by PET scans are established as biomarkers of Alzheimer’s disease (AD), they can emerge decades before symptoms are detectable on traditional neuropsychological (NP) tests. There is a pressing need for early AD detection tools that are more accessible, cost-effective, and non-invasive. The digital clock drawing test (dCDT), a digital version of the clock drawing test, has emerged as a promising cognitive assessment tool that takes minutes to administer and can reveal clinical symptoms earlier than paper–pencil NP tests. This study explored the association between 53 dCDT measures and amyloid and tau PET biomarkers using data from 87 low age risk participants in the Framingham Heart Study. Our findings revealed a significant association between a dCDT measure related to spatial reasoning function and global amyloid burden (P < 0.05), and 4 dCDT measures correlated with tau accumulation after adjusting for multiple comparisons. Notably, the combination of demographic variables and a composite dCDT score achieved a mean area under the receiver operating characteristics curve of 0.86 in detecting amyloid positivity. These results highlight the potential of dCDT measures as effective predictors of amyloid and tau pathology in preclinical AD.https://doi.org/10.1038/s41598-025-95852-8Digital clock drawing testAmyloidTauPETAssociation
spellingShingle Huitong Ding
Chenglin Lyu
Cody Karjadi
Preeti Sunderaraman
Christina B. Young
Elizabeth C. Mormino
Spencer Low
Sherral Devine
Katherine Gifford
Rhoda Au
Honghuang Lin
Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
Scientific Reports
Digital clock drawing test
Amyloid
Tau
PET
Association
title Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
title_full Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
title_fullStr Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
title_full_unstemmed Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
title_short Association of the digital clock drawing test with amyloid and tau PET biomarkers in low age risk adults
title_sort association of the digital clock drawing test with amyloid and tau pet biomarkers in low age risk adults
topic Digital clock drawing test
Amyloid
Tau
PET
Association
url https://doi.org/10.1038/s41598-025-95852-8
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