Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology
Renaud La Joie, Nagehan Ayakta, William W Seeley, Ewa Borys, Adam L Boxer, Charles DeCarli, Vincent Doré, Lea T Grinberg, Eric Huang, Ji-Hye Hwang, Milos D Ikonomovic, Clifford Jack Jr, William J Jagust, Lee-Way Jin, William E Klunk, Julia Kofler, Orit H Lesman-Segev, Samuel N Lockhart, Val J Lowe, Colin L Masters, Chester A Mathis, Catriona L McLean, Bruce L Miller, Daniel Mungas, James P O'Neil, John M Olichney, Joseph E Parisi, Ronald C Petersen, Howard J Rosen, Christopher C Rowe, Salvatore Spina, Prashanthi Vemuri, Victor L Villemagne, Melissa E Murray, Gil D Rabinovici, Renaud La Joie, Nagehan Ayakta, William W Seeley, Ewa Borys, Adam L Boxer, Charles DeCarli, Vincent Doré, Lea T Grinberg, Eric Huang, Ji-Hye Hwang, Milos D Ikonomovic, Clifford Jack Jr, William J Jagust, Lee-Way Jin, William E Klunk, Julia Kofler, Orit H Lesman-Segev, Samuel N Lockhart, Val J Lowe, Colin L Masters, Chester A Mathis, Catriona L McLean, Bruce L Miller, Daniel Mungas, James P O'Neil, John M Olichney, Joseph E Parisi, Ronald C Petersen, Howard J Rosen, Christopher C Rowe, Salvatore Spina, Prashanthi Vemuri, Victor L Villemagne, Melissa E Murray, Gil D Rabinovici
Abstract
Introduction: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11C]PIB-positron emission tomography ([11C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification.
Methods: Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings.
Results: CL values increased with each CERAD neuritic plaque score increment (median -3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET-pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate-to-high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%).
Discussion: Our study demonstrated the robustness of a multisite Centiloid [11C]PIB-PET study and established a range of pathology-based CL thresholds.
Keywords: Alzheimer's disease neuropathologic changes; CERAD; Centiloid; Harmonization; Neuropathology; Pittsburgh compound-B; Positron emission tomography; Thal; Threshold; β-amyloid.
Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Figures
![Figure 1.. Overview of the present study.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6368897/bin/nihms-1507069-f0001.jpg)
Figure 2.. Relationships between CL values and…
Figure 2.. Relationships between CL values and post mortem measures of Aβ pathology (A) and…
Figure 3.. Complementary analyses
A) Robust associations…
Figure 3.. Complementary analyses
A) Robust associations between CL values and CERAD scores across centers.…
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- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aged
- Alzheimer Disease* / diagnostic imaging
- Alzheimer Disease* / pathology
- Aniline Compounds*
- Autopsy*
- Female
- Humans
- Male
- Neuropathology*
- Plaque, Amyloid* / diagnostic imaging
- Plaque, Amyloid* / pathology
- Positron-Emission Tomography*
- Retrospective Studies
- Thiazoles*
- 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
- Aniline Compounds
- Thiazoles
- R01 NS017950/NS/NINDS NIH HHS/United States
- P50 AG016574/AG/NIA NIH HHS/United States
- K24 AG053435/AG/NIA NIH HHS/United States
- R01 AG027859/AG/NIA NIH HHS/United States
- R01 AG027984/AG/NIA NIH HHS/United States
- P01 AG019724/AG/NIA NIH HHS/United States
- R01 AG021028/AG/NIA NIH HHS/United States
- R01 AG031563/AG/NIA NIH HHS/United States
- P30 AG010129/AG/NIA NIH HHS/United States
- R01 AG045611/AG/NIA NIH HHS/United States
- P01 AG025204/AG/NIA NIH HHS/United States
- U01 AG006786/AG/NIA NIH HHS/United States
- R01 AG034570/AG/NIA NIH HHS/United States
- R01 AG041851/AG/NIA NIH HHS/United States
- P50 AG023501/AG/NIA NIH HHS/United States
- P50 AG005142/AG/NIA NIH HHS/United States
- K24 AG045333/AG/NIA NIH HHS/United States
- R01 AG056366/AG/NIA NIH HHS/United States
- R01 AG038791/AG/NIA NIH HHS/United States
- R01 AG054449/AG/NIA NIH HHS/United States
- R01 AG058676/AG/NIA NIH HHS/United States
- R01 AG011378/AG/NIA NIH HHS/United States
- P30 AG049638/AG/NIA NIH HHS/United States
- P01 AG012435/AG/NIA NIH HHS/United States
- R01 AG032306/AG/NIA NIH HHS/United States
- P50 AG005133/AG/NIA NIH HHS/United States
- K23 AG031861/AG/NIA NIH HHS/United States
- RF1 AG025516/AG/NIA NIH HHS/United States
- R01 NS097495/NS/NINDS NIH HHS/United States
![Figure 2.. Relationships between CL values and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6368897/bin/nihms-1507069-f0002.jpg)
Figure 3.. Complementary analyses
A) Robust associations…
Figure 3.. Complementary analyses
A) Robust associations between CL values and CERAD scores across centers.…
![Figure 3.. Complementary analyses](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6368897/bin/nihms-1507069-f0003.jpg)
Source: PubMed