Renaud La Joie1, Nagehan Ayakta2, William W Seeley3, Ewa Borys4, Adam L Boxer3, Charles DeCarli5, Vincent Doré6, Lea T Grinberg3, Eric Huang3, Ji-Hye Hwang3, Milos D Ikonomovic7, Clifford Jack8, William J Jagust9, Lee-Way Jin10, William E Klunk11, Julia Kofler12, Orit H Lesman-Segev3, Samuel N Lockhart13, Val J Lowe14, Colin L Masters15, Chester A Mathis16, Catriona L McLean17, Bruce L Miller3, Daniel Mungas5, James P O'Neil18, John M Olichney5, Joseph E Parisi19, Ronald C Petersen20, Howard J Rosen3, Christopher C Rowe6, Salvatore Spina3, Prashanthi Vemuri8, Victor L Villemagne21, Melissa E Murray22, Gil D Rabinovici2. 1. Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: Renaud.lajoie@ucsf.edu. 2. Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA. 3. Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. 4. Department of Pathology, Stritch School of Medicine, Loyola University, Maywood, IL, USA. 5. Department of Neurology, University of California, Davis, CA, USA. 6. Department of Molecular Imaging & Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia. 7. Department of Neurology, University of Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, PA, USA. 8. Department of Radiology, Mayo Clinic, Rochester, MN, USA. 9. Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA. 10. Alzheimer's Disease Center, Department of Pathology, University of California Davis, CA, USA. 11. Department of Neurology, University of Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, PA, USA. 12. Department of Pathology, University of Pittsburgh, Pennsylvania, USA. 13. Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA; Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA. 14. Department of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA. 15. The Florey Institute, The University of Melbourne, Melbourne, Victoria, Australia. 16. Department of Radiology, University of Pittsburgh, PA, USA. 17. Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia. 18. Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA; Biomedical Isotope Facility, MBIB Division, Lawrence Berkeley National Laboratory, CA, USA. 19. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. 20. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 21. Department of Molecular Imaging & Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia; The Florey Institute, The University of Melbourne, Melbourne, Victoria, Australia. 22. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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.
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.
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