Defining Imaging Biomarker Cut Points For Brain Aging And Alzheimer's Disease

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

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 clinically 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 clinically 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 clinically impaired versus young CN method and base conservative cut points on the accuracy of clinically impaired versus age-matched CN method.

Keywords:
Alzheimer's disease, Alzheimer's imaging, Alzheimer's MRI, Amyloid PET, Tau PET, FDG PET, Alzheimer's biomarkers, Quantitative imaging

Citation: Clifford R. Jack Jr, Heather J. Wiste, Stephen D. Weigand, Terry M. Therneau, Val J. Lowe, David S. Knopman, Jeffrey L. Gunter, Matthew L. Senjem, David T. Jones, Kejal Kantarci, Mary M. Machulda, Michelle M. Mielke, Rosebud O. Roberts, Prashanthi Vemuri, Denise Reyes, Ronald C. Petersen Defining Imaging Biomarker Cut Points For Brain Aging And Alzheimer's Disease DOI: http://dx.doi.org/10.1016/j.jalz.2016.08.005

Published online: September 30, 2016

Copyright: © 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Acknowledgments
This study was supported by the National Institute of Health (R01 AG011378, R01 AG041851, U01 AG006786, and R01
AG034676), the GHR Foundation, and the Alexander.

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