A European multicentre PET study of fibrillar amyloid in Alzheimer's disease

Agneta Nordberg, Stephen F. Carter, Juha Rinne, Alexander Drzezga, David J. Brooks, Rik Vandenberghe, Daniela Perani, Anton Forsberg, Bengt Långström, Noora Scheinin, Mira Karrasch, Kjell Någren, Timo Grimmer, Isabelle Miederer, Paul Edison, Aren Okello, Koen Van Laere, Natalie Nelissen, Mathieu Vandenbulcke, Valentina GaribottoOve Almkvist, Elke Kalbe, Rainer Hinz, Karl Herholz

Research output: Contribution to journalArticle

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Abstract

Purpose: Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. Methods: In this study 238 [11C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [11C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. Results: [11C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [11C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [11C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p <0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. Conclusion: This study demonstrated the robustness of [11C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Amyloid
Multicenter Studies
Alzheimer Disease
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Brain
Apolipoprotein E4
Apolipoproteins E
Biomarkers
Genotype

Keywords

  • Alzheimer's disease
  • Amyloid
  • Cognition
  • MCI
  • Mild cognitive impairment
  • Multicentre PET
  • PIB

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Nordberg, A., Carter, S. F., Rinne, J., Drzezga, A., Brooks, D. J., Vandenberghe, R., ... Herholz, K. (2013). A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. European Journal of Nuclear Medicine and Molecular Imaging, 40(1), 104-114. https://doi.org/10.1007/s00259-012-2237-2

A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. / Nordberg, Agneta; Carter, Stephen F.; Rinne, Juha; Drzezga, Alexander; Brooks, David J.; Vandenberghe, Rik; Perani, Daniela; Forsberg, Anton; Långström, Bengt; Scheinin, Noora; Karrasch, Mira; Någren, Kjell; Grimmer, Timo; Miederer, Isabelle; Edison, Paul; Okello, Aren; Van Laere, Koen; Nelissen, Natalie; Vandenbulcke, Mathieu; Garibotto, Valentina; Almkvist, Ove; Kalbe, Elke; Hinz, Rainer; Herholz, Karl.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 40, No. 1, 01.2013, p. 104-114.

Research output: Contribution to journalArticle

Nordberg, A, Carter, SF, Rinne, J, Drzezga, A, Brooks, DJ, Vandenberghe, R, Perani, D, Forsberg, A, Långström, B, Scheinin, N, Karrasch, M, Någren, K, Grimmer, T, Miederer, I, Edison, P, Okello, A, Van Laere, K, Nelissen, N, Vandenbulcke, M, Garibotto, V, Almkvist, O, Kalbe, E, Hinz, R & Herholz, K 2013, 'A European multicentre PET study of fibrillar amyloid in Alzheimer's disease', European Journal of Nuclear Medicine and Molecular Imaging, vol. 40, no. 1, pp. 104-114. https://doi.org/10.1007/s00259-012-2237-2
Nordberg, Agneta ; Carter, Stephen F. ; Rinne, Juha ; Drzezga, Alexander ; Brooks, David J. ; Vandenberghe, Rik ; Perani, Daniela ; Forsberg, Anton ; Långström, Bengt ; Scheinin, Noora ; Karrasch, Mira ; Någren, Kjell ; Grimmer, Timo ; Miederer, Isabelle ; Edison, Paul ; Okello, Aren ; Van Laere, Koen ; Nelissen, Natalie ; Vandenbulcke, Mathieu ; Garibotto, Valentina ; Almkvist, Ove ; Kalbe, Elke ; Hinz, Rainer ; Herholz, Karl. / A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. In: European Journal of Nuclear Medicine and Molecular Imaging. 2013 ; Vol. 40, No. 1. pp. 104-114.
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T1 - A European multicentre PET study of fibrillar amyloid in Alzheimer's disease

AU - Nordberg, Agneta

AU - Carter, Stephen F.

AU - Rinne, Juha

AU - Drzezga, Alexander

AU - Brooks, David J.

AU - Vandenberghe, Rik

AU - Perani, Daniela

AU - Forsberg, Anton

AU - Långström, Bengt

AU - Scheinin, Noora

AU - Karrasch, Mira

AU - Någren, Kjell

AU - Grimmer, Timo

AU - Miederer, Isabelle

AU - Edison, Paul

AU - Okello, Aren

AU - Van Laere, Koen

AU - Nelissen, Natalie

AU - Vandenbulcke, Mathieu

AU - Garibotto, Valentina

AU - Almkvist, Ove

AU - Kalbe, Elke

AU - Hinz, Rainer

AU - Herholz, Karl

PY - 2013/1

Y1 - 2013/1

N2 - Purpose: Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. Methods: In this study 238 [11C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [11C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. Results: [11C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [11C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [11C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p <0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. Conclusion: This study demonstrated the robustness of [11C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.

AB - Purpose: Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. Methods: In this study 238 [11C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [11C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. Results: [11C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [11C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [11C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p <0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. Conclusion: This study demonstrated the robustness of [11C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.

KW - Alzheimer's disease

KW - Amyloid

KW - Cognition

KW - MCI

KW - Mild cognitive impairment

KW - Multicentre PET

KW - PIB

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