Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients

Author:

Altomare Daniele123,Barkhof Frederik45,Caprioglio Camilla12,Collij Lyduine E.4,Scheltens Philip6,Lopes Alves Isadora4,Bouwman Femke6,Berkhof Johannes7,van Maurik Ingrid S.67,Garibotto Valentina89,Moro Christian12,Delrieu Julien1011,Payoux Pierre1213,Saint-Aubert Laure1213,Hitzel Anne12,Molinuevo José Luis1415,Grau-Rivera Oriol141617,Gispert Juan Domingo141618,Drzezga Alexander192021,Jessen Frank202223,Zeyen Philip22,Nordberg Agneta2425,Savitcheva Irina26,Jelic Vesna27,Walker Zuzana2829,Edison Paul30,Demonet Jean-François31,Gismondi Rossella32,Farrar Gill33,Stephens Andrew W.32,Frisoni Giovanni B.12,Abdelnour Carla34,Aguilera Nuria34,Aksman Leon34,Alarcón-Martín Emilio34,Alegret Montse34,Alonso-Lana Silvia34,Altomare Daniele34,Andersen Pia34,Arab Majd34,Aspö Malin34,Bader Ilona34,Bader Ilse34,Banton Nigel34,Barkhof Frederik34,Barnes Rodrigo34,Barrie Dawn34,Battle Mark34,Belén Collado Ana34,Bellet Julie34,Berkhof Johannes34,Biger Marine34,Birck Cindy34,Bischof Gerard34,Boada Mercè34,Boellaard Ronald34,Bogdanovic Nenad34,Bollack Ariane34,Bombois Stéphanie34,Borg Stefan34,Borjesson-Hanson Anne34,Boskov Vladimir34,Boutantin Justine34,Boutoleau-Bretonniere Claire34,Bouwman Femke34,Breuilh Laetitia34,Bringman Eva34,Brunel Baptiste34,Bucci Marco34,Buckley Chris34,Buendía Mar34,Bullich Santi34,Calvet Anna34,Cañada Laia34,Cañada Marta34,Caprioglio Camilla34,Cardoso Jorge34,Carlier Jasmine34,Carre Elise34,Carrie Isabelle34,Cassagnaud Pascaline34,Cassol Emmanuelle34,Castilla-Martí Miguel34,Cazalon Elodie34,Chaarriau Tiphaine34,Chaigeau Rachel34,Chalmers Taylor34,Clerc Marie-Thérèse34,Clerigue Montserrat34,Cognat Emmanuel34,Coll Nina34,Collij Lyduine E.34,Connely Peter34,Cordier Elodie34,Costes Corine34,Coulange Camille34,Courtemanche Hélène34,Creisson Eric34,Crinquette Charlotte34,Cuevas Rosario34,Cufi Marie-Noëlle34,Dardenne Sophie34,de Arriba Maria34,de Costa Luis Casper34,de Gier Yvonne34,de Verbizier Lonjon Delphine34,Dekker Veronique34,Dekyndt Bérengère34,Delbeuck Xavier34,Delrieu Julien34,Demonet Jean-François34,Deramecourt Vincent34,Desclaux Françoise34,Diaz Carlos34,Diego Susana34,Djafar Mehdi34,Dölle Britta34,Doull Laura34,Dricot Laurence34,Drzezga Alexander34,Dubois Bruno34,Dumont Julien34,Dumur Jean34,Dumurgier Julien34,Dvorak Martin34,Ecay Mirian34,Edison Paul34,Escher Claus34,Estanga Ainara34,Esteban Ester34,Fanjaud Guy34,Farrar Gill34,Fauria Karine34,Felez Sanchez Marta34,Feukam Talla Patrick34,Ford Lisa34,Frisoni Giovanni B.34,Fuster David34,Gabelle Audrey34,Garibotto Valentina34,Gaubert Sinead34,Gauci Cédric34,Geldhof Christine34,Georges Jean34,Ghika Joseph34,Gismondi Rossella34,Gispert Juan Domingo34,González Elena34,Goovaerts Valerie34,Goulart Denis Mariano34,Grasselli Caroline34,Grau-Rivera Oriol34,Gray Katherine34,Greensmith Martin34,Grozn Laure34,Guillemaud Céline34,Gunn Fiona34,Guntur Ramkumar Prasad34,Hagman Göran34,Hansseuw Bernard34,Heeman Fiona34,Hendriks Janine34,Himmelmann Jakob34,Hitzel Anne34,Hives Florent34,Hoenig Merle34,Hourrègue Claire34,Hudson Justine34,Huguet Jordi34,Ibarria Marta34,Iidow Ifrah34,Indart Sandrine34,Ingala Silvia34,Ivanoiu Adrian34,Jacquemont Charlotte34,Jelic Vesna34,Jessen Frank34,Jiao Jieqing34,Jofresa Sara34,Jonsson Cathrine34,Kaliukhovich Dzmitry34,Kern Silke34,Kivipelto Miia34,Knezevic Iva34,Kuchcinski Grégory34,Laforce Manon34,Lafuente Asunción34,Lala Françoise34,Lammertsma Adriaan34,Lax Michelle34,Lebouvier Thibaud34,Lee Ho-Yun34,Lee Lean34,Leeuwis Annebet34,Lefort Amandine34,Legrand Jean-François34,Leroy Mélanie34,Lesoil Markowski Constance34,Levy Marcel34,Lhommel  Renaud34,Lopes Renaud34,Lopes Alves Isadora34,Lorenzini Luigi34,Lorette Adrien34,Luckett Emma34,Lundin Marie34,Mackowiak Marie-Anne34,Malotaux Vincent34,Manber Richard34,Manyakov Nikolay34,Markiewicz Pawel34,Marne Paula34,Marquié Marta34,Martín Elvira34,Martínez Joan34,Martinez Lage Pablo34,Mastenbroek Sophie E.34,Maureille Aurélien34,Meersmans Karen34,Mett Anja34,Milne Joseph34,Minguillón Carolina34,Modat Marc34,Molinuevo José Luis34,Montrreal Laura34,Moro Christian34,Müller Theresa34,Muniz Graciela34,Mutsarts Henk Jan34,Nilsson Ted34,Ninerola Aida34,Nordberg Agneta34,Novaes Wilse34,Nuno Carmelo Pires Silva Joao34,Operto Greg34,Orellana Adela34,Ousset Pierre-Jean34,Outteryck Olivier34,Pallardy Amandine34,Palombit Alessandro34,Pancho Ana34,Pappon Martin34,Paquet Claire34,Pariente Jérémie34,Pasquier Florence34,Payoux Pierre34,Peaker Harry34,Pelejà Esther34,Pennetier Delphine34,Pérez-Cordón Alba34,Perissinotti Andrés34,Perrenoud Matthieu Paul34,Petit Sandrine34,Petyt Grégory34,Pfeil Julia34,Pirotte Blanche34,Pla Sandra34,Plaza Wuthrich Sonia34,Poitrine Lea34,Pollet Marianne34,Poncelet Jean-Benoit34,Prior John34,Pruvo Jean-Pierre34,Putallaz Pauline34,Queneau Mathieu34,Quenon  Lisa34,Rădoi Andreea34,Rafiq Marie34,Ramage Fiona34,Ramis Maribel34,Reinwald Michael34,Rios Gonzalo34,Ritchie Craig34,Rodriguez Elena34,Rollin Adeline34,Rouaud Olivier34,Sacuiu Simona34,Saint-Aubert Laure34,Sala Arianna34,Salabert Anne-Sophie34,Saldias Jon34,Salvadó Gemma34,Sanabria Angela34,Sannemann Lena34,Sastre Nathalie34,Savina Daniela34,Savitcheva Irina34,Schaeverbeke Jolien34,Scheltens Philip34,Schildermans Carine34,Schmidt Mark34,Schöll Michael34,Schuermans Jeroen34,Semah Franck34,Shekari Mahnaz34,Skoog Ingmar34,Sotolongo-Grau Oscar34,Stephens Andrew34,Stewart Tiffany34,Stutzmann Jennyfer34,Tait Murray34,Tárraga Lluis34,Tartari Juan Pablo34,Tysen-backstrom Ann-christine34,Valero Sergi34,Vallez Garcia David34,van Berckel Bart N.M.34,van Essen Martijn34,Van Laere Koen34,van Leur Jeroen34,van Maurik Ingrid S.34,Vandenberghe Rik34,Vellas Bruno34,Virolinen Jukka34,Visser Pieter Jelle34,Walker Zuzana34,Walles Håkan34,Wallin Emilia34,Whitelaw Grant34,Wimberley Catriona34,Win          Zarni34,Wink Alle Meije34,Wolz Robin34,Woodside John34,Yaqub Maqsood34,Zettergren Anna34,Zeyen Philip34,

Affiliation:

1. Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland

2. Geneva Memory Center, Geneva University Hospitals, Geneva, Switzerland

3. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

4. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (UMC)–Location VUmc, Amsterdam, the Netherlands

5. Institute of Neurology, Institute of Healthcare Engineering, University College London, London, United Kingdom

6. Alzheimer Center, Department of Neurology, Amsterdam University Medical Centers–Location VUmc, Amsterdam, the Netherlands

7. Department of Epidemiology and Data Science, Amsterdam University Medical Centers–Location VUmc, Amsterdam, the Netherlands

8. Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland

9. Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland

10. Gérontopôle, Department of Geriatrics, Toulouse University Hospital, Toulouse, France

11. Maintain Aging Research Team, CERPOP, Inserm, Université Paul Sabatier, Toulouse, France

12. Department of Nuclear Medicine, Toulouse University Hospital, Toulouse, France

13. Toulouse NeuroImaging Center (ToNIC), UMR1214 Inserm, Université de Toulouse III, Toulouse, France

14. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain

15. H. Lundbeck, Copenhagen, Denmark

16. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

17. Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain

18. Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain

19. Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

20. German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany

21. Institute of Neuroscience and Medicine (INM-2), Molecular Organization of the Brain, Forschungszentrum Jülich, Germany

22. Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

23. Excellence Cluster Cellular Stress Responses in Aging-Related Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany

24. Department of Neurobiology, Care Sciences and Society, Center of Alzheimer Research, Karolinska Institutet, Stockholm, Sweden

25. Theme Aging, Karolinska University Hospital, Stockholm, Sweden

26. Medical Radiation Physics and Nuclear Medicine, Section for Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden

27. Cognitive Disorders Clinic, Theme Inflammation and Aging, Karolinska University Hospital–Huddinge, Stockholm, Sweden

28. Division of Psychiatry, University College London, London, United Kingdom

29. St Margaret’s Hospital, Essex Partnership University NHS Foundation Trust, Essex, United Kingdom

30. Division of Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom

31. Leenaards Memory Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland

32. Life Molecular Imaging, Berlin, Germany

33. GE Healthcare, Amersham, United Kingdom

34. for the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) Consortium

Abstract

ImportanceAmyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect.ObjectiveTo assess the clinical effect of amyloid PET in memory clinic patients.Design, Setting, and ParticipantsThe AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023.InterventionAmyloid PET.Main Outcome and MeasureThe main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months.ResultsA total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of 260 (11%) in arm 2 (P < .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P < .001; MCI: 45/108 [42%] vs 9/102 [9%]; P < .001; dementia: 39/80 [49%] vs 16/80 [20%]; P < .001).Conclusion and RelevanceIn this study, early amyloid PET allowed memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months compared with patients who had not undergone amyloid PET. These findings support the implementation of amyloid PET early in the diagnostic workup of memory clinic patients.Trial RegistrationEudraCT Number: 2017-002527-21

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

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