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Cited by 186Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

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

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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·2013·European Journal of Nuclear Medicine and Molecular Imaging
DOI 10.1007/s00259-012-2237-2PMC PMC3510420
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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 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]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: [(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]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 [(11)C]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 [(11)C]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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Fig. 1 PIB retention ratios in cortical (a) and subcortical (b) brain regions in 51 healthy controls, 72 patients with MCI and 97 patients with AD. Regional [11C]PIB retention is expressed as retentions relative to cerebellar grey matter. Mean values ± SD are shown. *p < 0.05, **p < 0.01, ***p < 0.001, controls versus MCI and controls versus AD; # p < 0.05, ## p < 0.01, ### p < 0.001, MCI versus AD
Fig. 1 PIB retention ratios in cortical (a) and subcortical (b) brain regions in 51 healthy controls, 72 patients with MCI and 97 patients with AD. Regional [11C]PIB retention is expressed as retentions relative to cerebellar grey matter. Mean values ± SD are shown. *p < 0.05, **p < 0.01, ***p < 0.001, controls versus MCI and controls versus AD; # p < 0.05, ## p < 0.01, ### p < 0.001, MCI versus ADCC BY · PubMed Central
Fig. 2 Representative PET scans of healthy controls, patients with MCI and patients with AD from five different centres. The imaging acquisition parameters and mean injected doses used at each centre are presented in the Materials and methods section. Four centres used the HR+ scanner, and centre E used the GE Advance scanner. The images have different visual properties as the centres used different reconstruction parameters, filters and smoothing kernels (see Supplementary Table 2). Colour scale PIB retention (red high, green intermediate, blue low)
Fig. 2 Representative PET scans of healthy controls, patients with MCI and patients with AD from five different centres. The imaging acquisition parameters and mean injected doses used at each centre are presented in the Materials and methods section. Four centres used the HR+ scanner, and centre E used the GE Advance scanner. The images have different visual properties as the centres used different reconstruction parameters, filters and smoothing kernels (see Supplementary Table 2). Colour scale PIB retention (red high, green intermediate, blue low)CC BY · PubMed Central
Fig. 3 Cortical [11C]PIB retention ratios in controls, patients with MCI and patients with AD investigated at five different centres (A–E)
Fig. 3 Cortical [11C]PIB retention ratios in controls, patients with MCI and patients with AD investigated at five different centres (A–E)CC BY · PubMed Central
Fig. 4 Distribution of neocortical [11C]PIB retention ratios in healthy controls. The 95 % upper confidence limit for a normal PIB retention ratio in the healthy controls was defined as 1.41
Fig. 4 Distribution of neocortical [11C]PIB retention ratios in healthy controls. The 95 % upper confidence limit for a normal PIB retention ratio in the healthy controls was defined as 1.41CC BY · PubMed Central
Fig. 5 Dementia-free survival in 64 patients with MCI at 28 ± 15 months. None of 21 MCI PIB-negative patients converted to AD while 67.4 % of the MCI PIB-positive patients converted to AD. No difference in conversion rate was observed between MCI patients with relatively high (retention ratio above median) and lower (but retention ratio still >1.41) [11C]PIB retention
Fig. 5 Dementia-free survival in 64 patients with MCI at 28 ± 15 months. None of 21 MCI PIB-negative patients converted to AD while 67.4 % of the MCI PIB-positive patients converted to AD. No difference in conversion rate was observed between MCI patients with relatively high (retention ratio above median) and lower (but retention ratio still >1.41) [11C]PIB retentionCC BY · PubMed Central

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Research works printed but not linked: 1

  1. Collignon A, Maes F, Delaere D, Vandermeulen D, Suetens P, Marchal G. Automated multi-modality image registration based on information theory. Proceedings of the International Conference on Information Processing in Medical Imaging. Dordrecht: Kluwer Academic; 1995.

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Metadata

Authors
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., Garibotto, V., Almkvist, O., Kalbe, E., Hinz, R., & Herholz, K.
Affiliations
  • Karolinska University Hospital (SE)
  • Karolinska Institutet (SE)
  • University of Turku (FI)
  • Technical University of Munich (DE)
  • Imperial College London (GB)
  • KU Leuven (BE)
  • Vita-Salute San Raffaele University (IT)
  • Uppsala University (SE)
  • University of Vechta (DE)
  • University of Manchester (GB)
Corresponding author
Nordberg, Agneta
ORCID
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Publisher
Springer Science and Business Media LLC
Published
2012-09-08
Volume
40
Issue
1
Pages
104-114
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
DOI
10.1007/s00259-012-2237-2
PMC
PMC3510420
OpenAlex
W2116591217
Cited by
186
References
46
Citations by year
2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 11 · 2021: 13 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 14 · 2016: 25 · 2015: 27 · 2014: 27 · 2013: 24 · 2012: 2
FWCI
18.28
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Lirias (KU Leuven) (submittedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • Åbo Akademi University Research Portal (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Alzheimer's Research Trust
  • Deutsche Forschungsgemeinschaft (DR 445/3-1, DR 445/4-1)
  • Academy of Finland
  • Belgian Federal Science Policy Office (IUAP P6/29)
  • Fonds Wetenschappelijk Onderzoek (05/014, G0668.07, P6/29, G0076.02)
  • Karolinska Institutet (05817)
  • Stockholms Läns Landsting
  • Vetenskapsrådet (05817)
  • Technische Universität München
  • Swedish Brain Power (05817)
  • Universität zu Köln
  • Turun Yliopistollinen Keskussairaala
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
Alzheimer's disease, amyloid PET, Pittsburgh compound B, mild cognitive impairment, prodromal Alzheimer's disease, APOE ε4, conversion to Alzheimer's disease, memory impairment, negative predictive value, amyloid biomarkers, longitudinal follow-up
MeSH terms
Aged, Alzheimer Disease, Amyloid, Aniline Compounds, Apolipoproteins E, Brain, Brain Chemistry, Europe, Female, Humans, Male, Middle Aged, Thiazoles, Case-Control Studies, Radiopharmaceuticals, Positron-Emission Tomography

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