Cited by 226Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Quantification of amyloid PET for future clinical use: a state-of-the-art review

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Pemberton, Hugh G., Collij, Lyduine E., Heeman, Fiona, Bollack, Ariane, Shekari, Mahnaz, Salvadó, Gemma, Alves, Isadora Lopes, Garcia, David Vallez +9 more·2022·European Journal of Nuclear Medicine and Molecular Imaging

Abstract

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer’s disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods.

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  • The range from 12 Centiloids to 30 Centiloids has been proposed to reflect the 'gray zone' of Aβ deposition.

    “Moreover, the range from 12 Centiloids to 30 Centiloids has been proposed to reflect the ‘gray zone’ of Aβ deposition24.”

    From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [24]

    The Centiloid scaling section says clinical studies have defined “grey zone” patient cut-offs, supporting the general idea. It does not give 12 and 30 Centiloids as the boundaries of that zone; the section instead mentions other thresholds, including an intermediate range of 20–40 CL for a clinical trial. No page number is available in our copy. (LLM, conf=0.86)

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Authors
Pemberton, H. G., Collij, L. E., Heeman, F., Bollack, A., Shekari, M., Salvadó, G., Alves, I. L., Garcia, D. V., Battle, M., Buckley, C., Stephens, A. W., Bullich, S., Garibotto, V., Barkhof, F., Gispert, J. D., Farrar, G., & on behalf of the AMYPAD consortium
Affiliations
  • UCL Queen Square Institute of Neurology (GB)
  • Amsterdam University Medical Centers (NL)
  • University College London (GB)
  • Universitat Pompeu Fabra (ES)
  • Lund University (SE)
  • University of Geneva (CH)
Corresponding author
Pemberton, Hugh G.
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Published
2022-04-07
Volume
49
Issue
10
Pages
3508-3528
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
OpenAlex
W4225623397
Cited by
226
References
220
Citations by year
2026: 61 · 2025: 71 · 2024: 64 · 2023: 25 · 2022: 5
FWCI
7.10
Type
journal article
Language
en
Open access
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
Innovative Medicines Initiative (115952)
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
amyloid PET quantification, amyloid-beta, Alzheimer's disease, fluorine-18 radiotracer, aducanumab, treatment response monitoring, cognitive decline prediction, patient selection for clinical trials, amyloid imaging
MeSH terms
Alzheimer Disease, Amyloid, Amyloidosis, Brain, Humans, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction

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