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Cognitive and functional patterns of nondemented subjects with equivocal visual amyloid PET findings

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Despite good to excellent inter-reader agreement in the evaluation of amyloid load on PET scans in subjects with Alzheimer's disease, some equivocal findings have been reported in the literature. We aimed to describe the clinical characteristics of subjects with equivocal PET images.

Methods

Nondemented subjects aged 70 years or more were enrolled from the MAPT trial. Cognitive and functional assessments were conducted at baseline, at 6 months, and annually for 3 years. During the follow-up period, 271 subjects had 18F-AV45 PET scans. Images were visually assessed by three observers and classified as positive, negative or equivocal (if one observer disagreed). After debate, equivocal images were reclassified as positive (EP+) or negative (EP−). Scans were also classified by semiautomated quantitative analysis using mean amyloid uptake of cortical regions. We evaluated agreement among the observers, and between visual and quantitative assessments using kappa coefficients, and compared the clinical characteristics of the subjects according to their PET results.

Results

In 158 subjects (58.30 %) the PET scan was negative for amyloid, in 77 (28.41 %) the scan was positive and in 36 (13.28 %) the scan was equivocal. Agreement among the three observers was excellent (kappa 0.80). Subjects with equivocal images were more frequently men (58 % vs. 37 %) and exhibited intermediate scores on cognitive and functional scales between those of subjects with positive and negative scans. Amyloid load differed between the EP− and negative groups and between the EP+ and positive groups after reclassification.

Conclusion

Equivocal amyloid PET images could represent a neuroimaging entity with intermediate amyloid load but without a specific neuropsychological pattern. Clinical follow-up to assess cognitive evolution in subjects with equivocal scans is needed.

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Compliance with ethical standards

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Conflicts of interest

Prof. Payoux served on the scientific advisory board of Avid Radiopharmaceuticals and GEHC.

Dr. Delrieu served on the scientific advisory board of Avid Radiopharmaceuticals.

Dr. Gallini reports no conflicts of interest.

Dr. Adel reports no conflicts of interest.

Dr. Salabert reports no conflicts of interest.

Dr. Hitzel reports no conflicts of interest.

Dr. Cantet reports no conflicts of interest.

Dr. Tafani reports no conflicts of interest.

Dr. De Verbizier reports no conflicts of interest.

Prof. Darcourt served on the scientific advisory board of Avid Radiopharmaceuticals.

Prof. Fernandez reports no conflicts of interest.

Prof. Monteil reports no conflicts of interest.

Dr. Carrié reports no conflicts of interest.

Dr. Voisin T reports no conflicts of interest.

Dr. Gillette-Guyonnet reports no conflicts of interest.

Dr. Pontecorvo is an employee of Avid Radiopharmaceuticals.

Prof. Vellas served on the scientific advisory board of Avid Radiopharmaceuticals.

Prof. Andrieu reports no conflicts of interest.

Funding

Supported by MAPT study (NCT01513252), The Avid Company and Labex IRON.

This study was also supported by grants from the French Ministry of Health (PHRC 2008), and the Institut de Recherche Pierre Fabre (manufacturer of the omega-3 supplement). This study was supported by the University Hospital Center of Toulouse. Biological sample collection was supported by Exhonit Therapeutics. The AV45-MAPT study was supported by Avid Radiopharmaceuticals Inc. and this work has been supported in part by a grant from the French National Agency for Research called “Investissements d’Avenir” n°ANR-11-LABX-0018-01.

Human rights and informed consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, CHU Toulouse, Purpan University Hospital, Toulouse, France

    P. Payoux, A. Hitzel & M. Tafani

  2. Inserm, Imagerie cérébrale et handicaps neurologiques, UMR 825, F-31059, Toulouse, France

    P. Payoux, D. Adel, A. S. Salabert & M. Tafani

  3. Université de Toulouse, UPS, Imagerie cérébrale et handicaps neurologiques, UMR 825, CHU Purpan, Place du Dr Baylac, F-31059, Toulouse, France

    P. Payoux, A. Gallini, A. Hitzel, C. Cantet, M. Tafani, T. Voisin, S. Gillette-Guyonnet, B. Vellas & S. Andrieu

  4. Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France

    J. Delrieu, A. Gallini, C. Cantet, I. Carrié, T. Voisin, S. Gillette-Guyonnet, B. Vellas & S. Andrieu

  5. INSERM UMR 1027, Toulouse, France

    J. Delrieu, A. Gallini, C. Cantet, T. Voisin, S. Gillette-Guyonnet, B. Vellas & S. Andrieu

  6. Department of Nuclear Medicine, Montpellier University Hospital, Montpellier, France

    D. De Verbizier

  7. Nuclear Medicine Department, Centre Antoine Lacassagne, Nice, France

    J. Darcourt

  8. University of Nice-Sophia Antipolis, Nice, France

    J. Darcourt

  9. Nuclear Medicine Department, Pellegrin University Hospital Bordeaux, Bordeaux, France

    Ph. Fernandez

  10. CNRS UMR 5287 – INCIA, Victor Segalen, University Bordeaux II, Bordeaux, France

    Ph. Fernandez

  11. Department of Nuclear Medicine, University Hospital, Limoges, France

    J. Monteil

  12. University of Limoges, Limoges, France

    J. Monteil

  13. Avid Radiopharmaceuticals, Philadelphia, PA, USA

    M. Pontecorvo

  14. Department of Epidemiology and Public Health, CHU Toulouse, Toulouse, France

    S. Andrieu

  15. INSERM U825, CHU Purpan, Place du Dr Baylac, 31059, Toulouse Cedex, France

    P. Payoux

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  1. P. Payoux
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  2. J. Delrieu
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Correspondence to P. Payoux.

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Appendix: members of the MAPT study group

Appendix: members of the MAPT study group

Principal investigator: Bruno Vellas (Toulouse); Coordination: Sophie Gillette-Guyonnet; Project leader: Isabelle Carrié; CRA: Lauréane Brigitte; Investigators: Catherine Faisant, Françoise Lala, Julien Delrieu; Psychologists: Emeline Combrouze, Carole Badufle, Audrey Zueras; Methodology, statistical analysis and data management: Sandrine Andrieu, Christelle Cantet, Virginie Gardette, Christophe Morin; Multidomain group: Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland (physical and nutritional components), Céline Caillaud, Pierre-Jean Ousset (cognitive component), Françoise Lala (preventive consultation) (Toulouse). The cognitive component was designed in collaboration with Sherry Willis from the University of Seattle, and Sylvie Belleville, Brigitte Gilbert and Francine Fontaine from the University of Montreal.

Co-Investigators in associated centres: Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda (Bordeaux); Marie-Noëlle-Cuffi, Corinne Costes (Castres); Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon (Dijon); Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron (Foix); Françoise Desclaux, Colette Blatge (Lavaur); Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud (Limoges); Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol (Lyon), Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart (Monaco); Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues (Montauban); Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays (Montpellier); Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien

Gonfrier (Nice); Yves Gasnier and Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles (Tarbes).

MRI group: Carole Dufouil (Bordeaux), Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia (Paris); Michèle Allard (Bordeaux); Frédéric Ricolfi (Dijon); Dominique Dubois (Foix); Marie Paule Bonceour Martel (Limoges); François Cotton (Lyon); Alain Bonafé (Montpellier); Stéphane Chanalet (Nice); Françoise Hugon (Tarbes); Fabrice Bonneville, Christophe Cognard, François Chollet (Toulouse).

PET scan group: Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, (Toulouse); Michèle Allard (Bordeaux); Michel Zanca (Montpellier); Jacques Monteil (Limoges); Jacques Darcourt (Nice).

Medico-economics group: Laurent Molinier, Hélène Derumeaux, Nadège Costa (Toulouse).

Biological sample collection: Christian Vincent, Bertrand Perret, Claire Vinel (Toulouse).

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Payoux, P., Delrieu, J., Gallini, A. et al. Cognitive and functional patterns of nondemented subjects with equivocal visual amyloid PET findings. Eur J Nucl Med Mol Imaging 42, 1459–1468 (2015). https://doi.org/10.1007/s00259-015-3067-9

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