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 R Jr. Jack, William J. Jagust, Lee Way Jin, William E. Klunk, Julia Kofler, Orit H. Lesman-Segev, Samuel N. Lockhart, Val Lowe, Colin L. Masters & 15 others Chester A. Mathis, Catriona L. McLean, Bruce L. Miller, Daniel Mungas, James P. O'Neil, John M. Olichney, Joseph E Parisi, Ronald Carl Petersen, Howard J. Rosen, Christopher C. Rowe, Salvatore Spina, Prashanthi D Vemuri, Victor L. Villemagne, Melissa E Murray, Gil D. Rabinovici

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalAlzheimer's and Dementia
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Amyloid Plaques
Area Under Curve
Alzheimer Disease
Pathology
Sensitivity and Specificity
Autopsy
Tomography
Neuropathology
N-methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole

Keywords

  • Alzheimer's disease neuropathologic changes
  • Centiloid
  • CERAD
  • 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
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. / La Joie, Renaud; Ayakta, Nagehan; Seeley, William W.; Borys, Ewa; Boxer, Adam L.; DeCarli, Charles; Doré, Vincent; Grinberg, Lea T.; Huang, Eric; Hwang, Ji Hye; Ikonomovic, Milos D.; Jack, Clifford R Jr.; Jagust, William J.; Jin, Lee Way; Klunk, William E.; Kofler, Julia; Lesman-Segev, Orit H.; Lockhart, Samuel N.; Lowe, Val; Masters, Colin L.; Mathis, Chester A.; McLean, Catriona L.; Miller, Bruce L.; Mungas, Daniel; O'Neil, James P.; Olichney, John M.; Parisi, Joseph E; Petersen, Ronald Carl; Rosen, Howard J.; Rowe, Christopher C.; Spina, Salvatore; Vemuri, Prashanthi D; Villemagne, Victor L.; Murray, Melissa E; Rabinovici, Gil D.

In: Alzheimer's and Dementia, Vol. 15, No. 2, 01.02.2019, p. 205-216.

Research output: Contribution to journalArticle

La Joie, R, Ayakta, N, Seeley, WW, Borys, E, Boxer, AL, DeCarli, C, Doré, V, Grinberg, LT, Huang, E, Hwang, JH, Ikonomovic, MD, Jack, CRJ, Jagust, WJ, Jin, LW, Klunk, WE, Kofler, J, Lesman-Segev, OH, Lockhart, SN, Lowe, V, Masters, CL, Mathis, CA, McLean, CL, Miller, BL, Mungas, D, O'Neil, JP, Olichney, JM, Parisi, JE, Petersen, RC, Rosen, HJ, Rowe, CC, Spina, S, Vemuri, PD, Villemagne, VL, Murray, ME & Rabinovici, GD 2019, 'Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology', Alzheimer's and Dementia, vol. 15, no. 2, pp. 205-216. https://doi.org/10.1016/j.jalz.2018.09.001
La Joie, Renaud ; Ayakta, Nagehan ; Seeley, William W. ; Borys, Ewa ; Boxer, Adam L. ; DeCarli, Charles ; Doré, Vincent ; Grinberg, Lea T. ; Huang, Eric ; Hwang, Ji Hye ; Ikonomovic, Milos D. ; Jack, Clifford R Jr. ; Jagust, William J. ; Jin, Lee Way ; Klunk, William E. ; Kofler, Julia ; Lesman-Segev, Orit H. ; Lockhart, Samuel N. ; Lowe, Val ; Masters, Colin L. ; Mathis, Chester A. ; McLean, Catriona L. ; Miller, Bruce L. ; Mungas, Daniel ; O'Neil, James P. ; Olichney, John M. ; Parisi, Joseph E ; Petersen, Ronald Carl ; Rosen, Howard J. ; Rowe, Christopher C. ; Spina, Salvatore ; Vemuri, Prashanthi D ; Villemagne, Victor L. ; Murray, Melissa E ; Rabinovici, Gil D. / Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 2. pp. 205-216.
@article{bb3b16c1d3e44123be64073d919a06b5,
title = "Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology",
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, Centiloid, CERAD, Harmonization, Neuropathology, Pittsburgh compound-B, Positron emission tomography, Thal, Threshold, β-amyloid",
author = "{La Joie}, Renaud and Nagehan Ayakta and Seeley, {William W.} and Ewa Borys and Boxer, {Adam L.} and Charles DeCarli and Vincent Dor{\'e} and Grinberg, {Lea T.} and Eric Huang and Hwang, {Ji Hye} and Ikonomovic, {Milos D.} and Jack, {Clifford R Jr.} and Jagust, {William J.} and Jin, {Lee Way} and Klunk, {William E.} and Julia Kofler and Lesman-Segev, {Orit H.} and Lockhart, {Samuel N.} and Val Lowe and Masters, {Colin L.} and Mathis, {Chester A.} and McLean, {Catriona L.} and Miller, {Bruce L.} and Daniel Mungas and O'Neil, {James P.} and Olichney, {John M.} and Parisi, {Joseph E} and Petersen, {Ronald Carl} and Rosen, {Howard J.} and Rowe, {Christopher C.} and Salvatore Spina and Vemuri, {Prashanthi D} and Villemagne, {Victor L.} and Murray, {Melissa E} and Rabinovici, {Gil D.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.jalz.2018.09.001",
language = "English (US)",
volume = "15",
pages = "205--216",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

AU - La Joie, Renaud

AU - Ayakta, Nagehan

AU - Seeley, William W.

AU - Borys, Ewa

AU - Boxer, Adam L.

AU - DeCarli, Charles

AU - Doré, Vincent

AU - Grinberg, Lea T.

AU - Huang, Eric

AU - Hwang, Ji Hye

AU - Ikonomovic, Milos D.

AU - Jack, Clifford R Jr.

AU - Jagust, William J.

AU - Jin, Lee Way

AU - Klunk, William E.

AU - Kofler, Julia

AU - Lesman-Segev, Orit H.

AU - Lockhart, Samuel N.

AU - Lowe, Val

AU - Masters, Colin L.

AU - Mathis, Chester A.

AU - McLean, Catriona L.

AU - Miller, Bruce L.

AU - Mungas, Daniel

AU - O'Neil, James P.

AU - Olichney, John M.

AU - Parisi, Joseph E

AU - Petersen, Ronald Carl

AU - Rosen, Howard J.

AU - Rowe, Christopher C.

AU - Spina, Salvatore

AU - Vemuri, Prashanthi D

AU - Villemagne, Victor L.

AU - Murray, Melissa E

AU - Rabinovici, Gil D.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease neuropathologic changes

KW - Centiloid

KW - CERAD

KW - Harmonization

KW - Neuropathology

KW - Pittsburgh compound-B

KW - Positron emission tomography

KW - Thal

KW - Threshold

KW - β-amyloid

UR - http://www.scopus.com/inward/record.url?scp=85057067485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057067485&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2018.09.001

DO - 10.1016/j.jalz.2018.09.001

M3 - Article

VL - 15

SP - 205

EP - 216

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 2

ER -