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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-01-2013 | Original Article

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

Authors: 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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2013

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.

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Title: A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease
Authors: 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
Publication date: 01-01-2013
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2013
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2237-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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