Defining imaging biomarker cut points for brain aging and Alzheimer's disease

Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D.; Therneau, Terry M.; Lowe, Val J.; Knopman, David S.; Gunter, Jeffrey L.; Senjem, Matthew L.; Jones, David T.; Kantarci, Kejal; Machulda, Mary M.; Mielke, Michelle M.; Roberts, Rosebud O.; Vemuri, Prashanthi; Reyes, Denise A.; Petersen, Ronald C.

doi:10.1016/j.jalz.2016.08.005

Cited by 931Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Defining imaging biomarker cut points for brain aging and Alzheimer's disease

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Jack, Clifford R., Wiste, Heather J., Weigand, Stephen D., Therneau, Terry M., Lowe, Val J., Knopman, David S., Gunter, Jeffrey L., Senjem, Matthew L. +8 more·2017·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2016.08.005PMC PMC5344738

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Abstract

INTRODUCTION: Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness. METHODS: We examined five methods for determining cut points. RESULTS: The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal. DISCUSSION: In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method.

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“18 F-flutemetamol, 18 F-florbetaben and 18 F-florbetapir tracers display 85%-98% sensitivity and 87%-100% specificity for Aβ plaques when using the postmortem truth standards of the Consortium to Establish a Registry for AD (CERAD) or the National Institute on Aging-Alzheimer's Association 85,[136][137][138] .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [138]

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[32]Klunk WE Cohen A Bi W Weissfeld L Aizenstein H McDade E Why we need two cutoffs for amyloid-imaging: Early versus Alzheimer’s-like amyloid-positivity P453 P4 Alzheimer’s Association International Conference Vancouver, British Columbia, Canada: Alzheimer’s Associaton 2012
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Authors: Jack, C. R., Wiste, H. J., Weigand, S. D., Therneau, T. M., Lowe, V. J., Knopman, D. S., Gunter, J. L., Senjem, M. L., Jones, D. T., Kantarci, K., Machulda, M. M., Mielke, M. M., Roberts, R. O., Vemuri, P., Reyes, D. A., & Petersen, R. C.
Affiliations: Mayo Clinic (US)
Corresponding author: Jack, Clifford R.
ORCID: Jack, Clifford R.
Wiste, Heather J.
Weigand, Stephen D.
Therneau, Terry M.
Lowe, Val J.
Knopman, David S.
Gunter, Jeffrey L.
Senjem, Matthew L.
Jones, David T.
Kantarci, Kejal
Machulda, Mary M.
Mielke, Michelle M.
Vemuri, Prashanthi
Petersen, Ronald C.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2016-09-30
Volume: 13
Issue: 3
Pages: 205-216
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2016.08.005
PMC: PMC5344738
OpenAlex: W2529649944
Cited by: 931
References: 46
Citations by year: 2026: 108 · 2025: 119 · 2024: 162 · 2023: 114 · 2022: 97 · 2021: 111 · 2020: 81 · 2019: 64 · 2018: 52 · 2017: 21 · 2016: 1
FWCI: 40.88
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Health (R01 AG011378, R01 AG041851, U01 AG006786, R01 AG034676)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: imaging biomarkers, cut points
MeSH terms: Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloidosis, Aniline Compounds, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Sensitivity and Specificity, Thiazoles, Fluorodeoxyglucose F18, Positron-Emission Tomography

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Defining imaging biomarker cut points for brain aging and Alzheimer's disease

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