Multisite study of the relationships between antemortem [ 11 C]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, William J. Jagust, Lee Way Jin, William E. Klunk, Julia Kofler, Orit H. Lesman-Segev, Samuel N. Lockhart, Val J. Lowe, Colin L. MastersChester 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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Introduction: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [ 11 C]PIB–positron emission tomography ([ 11 C]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 [ 11 C]PIB-PET study and established a range of pathology-based CL thresholds.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalAlzheimer's and Dementia
Volume15
Issue number2
DOIs
StatePublished - Feb 2019

Keywords

  • Alzheimer's disease neuropathologic changes
  • CERAD
  • Centiloid
  • Harmonization
  • Neuropathology
  • Pittsburgh compound-B
  • Positron emission tomography
  • Thal
  • Threshold
  • β-amyloid

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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