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 Garibotto; Ove Almkvist; Elke Kalbe; Rainer Hinz; Karl Herholz

doi:10.1007/s00259-012-2237-2

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 journal › Article › peer-review

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. © 2012 The Author(s).

Original language	English
Pages (from-to)	104-114
Number of pages	10
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	40
Issue number	1
DOIs	https://doi.org/10.1007/s00259-012-2237-2
Publication status	Published - Jan 2013

Keywords

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

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10.1007/s00259-012-2237-2

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Nordberg, A., Carter, S. F., Rinne, J., Drzezga, A., Brooks, D. J., 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., ... 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

@article{427bfb32185c430a9e913f8a1038fb87,

title = "A European multicentre PET study of fibrillar amyloid in Alzheimer's disease",

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. {\textcopyright} 2012 The Author(s).",

keywords = "Alzheimer's disease, Amyloid, Cognition, MCI, Mild cognitive impairment, Multicentre PET, PIB",

author = "Agneta Nordberg and Carter, {Stephen F.} and Juha Rinne and Alexander Drzezga and Brooks, {David J.} and Rik Vandenberghe and Daniela Perani and Anton Forsberg and Bengt L{\aa}ngstr{\"o}m and Noora Scheinin and Mira Karrasch and Kjell N{\aa}gren and Timo Grimmer and Isabelle Miederer and Paul Edison and Aren Okello and {Van Laere}, Koen and Natalie Nelissen and Mathieu Vandenbulcke and Valentina Garibotto and Ove Almkvist and Elke Kalbe and Rainer Hinz and Karl Herholz",

year = "2013",

month = jan,

doi = "10.1007/s00259-012-2237-2",

language = "English",

volume = "40",

pages = "104--114",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer Nature",

number = "1",

}

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

TY - JOUR

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. © 2012 The Author(s).

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. © 2012 The Author(s).

KW - Alzheimer's disease

KW - Amyloid

KW - Cognition

KW - MCI

KW - Mild cognitive impairment

KW - Multicentre PET

KW - PIB

U2 - 10.1007/s00259-012-2237-2

DO - 10.1007/s00259-012-2237-2

M3 - Article

C2 - 22961445

SN - 1619-7070

VL - 40

SP - 104

EP - 114

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 1

ER -

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

Abstract

Keywords

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