A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease
Open accessAbstract
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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Cognitively unimpaired individuals with abnormal amyloid biomarkers have more rapid progression of atrophy, hypometabolism, and clinical/cognitive decline than individuals without biomarker evidence of Aβ deposition.
“Numerous studies have shown that CU individuals with abnormal amyloid biomarkers have more rapid progression of atrophy, hypometabolism, and clinical/cognitive decline than individuals without biomarker evidence of Aβ deposition [13,33,80,93–99]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [94]
The Results section on longitudinal follow-up reports that PIB-positive patients with mild cognitive impairment converted to AD more often than PIB-negative patients. But the claim concerns cognitively unimpaired individuals: the Results section on cognitive impairment finds no significant relationship between PIB retention and cognitive scores in controls, and the paper does not report their longitudinal atrophy, hypometabolism, or clinical/cognitive decline. (LLM, conf=0.86)
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- 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
- Nordberg, Agneta
- Carter, Stephen F.
- Rinne, Juha
- Drzezga, Alexander
- Brooks, David J.
- Vandenberghe, Rik
- Perani, Daniela
- Forsberg, Anton
- Scheinin, Noora
- Karrasch, Mira
- Någren, Kjell
- Grimmer, Timo
- Miederer, Isabelle
- Edison, Paul
- Nelissen, Natalie
- Vandenbulcke, Mathieu
- Garibotto, Valentina
- Almkvist, Ove
- Kalbe, Elke
- Hinz, Rainer
- Herholz, Karl
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2012-09-08
- Volume
- 40
- Issue
- 1
- Pages
- 104-114
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- 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
- hybrid
- doi.org
- 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
- Health Sciences › Medicine › Physiology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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