Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients
Authors: Altomare Daniele , Barkhof Frederik , Caprioglio Camilla , Collij Lyduine E. , Scheltens Philip , Lopes Alves Isadora , Bouwman Femke , Berkhof Johannes , van Maurik Ingrid S. , Garibotto Valentina , Moro Christian , Delrieu Julien , Payoux Pierre , Saint-Aubert Laure , Hitzel Anne , Molinuevo José Luis , Grau-Rivera Oriol , Gispert Juan Domingo , Drzezga Alexander , Jessen Frank , Zeyen Philip , Nordberg Agneta , Savitcheva Irina , Jelic Vesna , Walker Zuzana , Edison Paul , Demonet Jean-François , Gismondi Rossella , Farrar Gill , Stephens Andrew W. , Frisoni Giovanni B. ,   Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) Consortium, Abdelnour Carla , Aguilera Nuria , Aksman Leon , Alarcón-Martín Emilio , Alegret Montse , Alonso-Lana Silvia , Altomare Daniele , Andersen Pia , Arab Majd , Aspö Malin , Bader Ilona , Bader Ilse , Banton Nigel , Barkhof Frederik , Barnes Rodrigo , Barrie Dawn , Battle Mark , Belén Collado Ana , Bellet Julie , Berkhof Johannes , Biger Marine , Birck Cindy , Bischof Gerard , Boada Mercè , Boellaard Ronald , Bogdanovic Nenad , Bollack Ariane , Bombois Stéphanie , Borg Stefan , Borjesson-Hanson Anne , Boskov Vladimir , Boutantin Justine , Boutoleau-Bretonniere Claire , Bouwman Femke , Breuilh Laetitia , Bringman Eva , Brunel Baptiste , Bucci Marco , Buckley Chris , Buendía Mar , Bullich Santi , Calvet Anna , Cañada Laia , Cañada Marta , Caprioglio Camilla , Cardoso Jorge , Carlier Jasmine , Carre Elise , Carrie Isabelle , Cassagnaud Pascaline , Cassol Emmanuelle , Castilla-Martí Miguel , Cazalon Elodie , Chaarriau Tiphaine , Chaigeau Rachel , Chalmers Taylor , Clerc Marie-Thérèse , Clerigue Montserrat , Cognat Emmanuel , Coll Nina , Collij Lyduine E. , Connely Peter , Cordier Elodie , Costes Corine , Coulange Camille , Courtemanche Hélène , Creisson Eric , Crinquette Charlotte , Cuevas Rosario , Cufi Marie-Noëlle , Dardenne Sophie , de Arriba Maria , de Costa Luis Casper , de Gier Yvonne , de Verbizier Lonjon Delphine , Dekker Veronique , Dekyndt Bérengère , Delbeuck Xavier , Delrieu Julien , Demonet Jean-François , Deramecourt Vincent , Desclaux Françoise , Diaz Carlos , Diego Susana , Djafar Mehdi , Dölle Britta , Doull Laura , Dricot Laurence , Drzezga Alexander , Dubois Bruno , Dumont Julien , Dumur Jean , Dumurgier Julien , Dvorak Martin , Ecay Mirian , Edison Paul , Escher Claus , Estanga Ainara , Esteban Ester , Fanjaud Guy , Farrar Gill , Fauria Karine , Felez Sanchez Marta , Feukam Talla Patrick , Ford Lisa , Frisoni Giovanni B. , Fuster David , Gabelle Audrey , Garibotto Valentina , Gaubert Sinead , Gauci Cédric , Geldhof Christine , Georges Jean , Ghika Joseph , Gismondi Rossella , Gispert Juan Domingo , González Elena , Goovaerts Valerie , Goulart Denis Mariano , Grasselli Caroline , Grau-Rivera Oriol , Gray Katherine , Greensmith Martin , Grozn Laure , Guillemaud Céline , Gunn Fiona , Guntur Ramkumar Prasad , Hagman Göran , Hansseuw Bernard , Heeman Fiona , Hendriks Janine , Himmelmann Jakob , Hitzel Anne , Hives Florent , Hoenig Merle , Hourrègue Claire , Hudson Justine , Huguet Jordi , Ibarria Marta , Iidow Ifrah , Indart Sandrine , Ingala Silvia , Ivanoiu Adrian , Jacquemont Charlotte , Jelic Vesna , Jessen Frank , Jiao Jieqing , Jofresa Sara , Jonsson Cathrine , Kaliukhovich Dzmitry , Kern Silke , Kivipelto Miia , Knezevic Iva , Kuchcinski Grégory , Laforce Manon , Lafuente Asunción , Lala Françoise , Lammertsma Adriaan , Lax Michelle , Lebouvier Thibaud , Lee Ho-Yun , Lee Lean , Leeuwis Annebet , Lefort Amandine , Legrand Jean-François , Leroy Mélanie , Lesoil Markowski Constance , Levy Marcel , Lhommel  Renaud , Lopes Renaud , Lopes Alves Isadora , Lorenzini Luigi , Lorette Adrien , Luckett Emma , Lundin Marie , Mackowiak Marie-Anne , Malotaux Vincent , Manber Richard , Manyakov Nikolay , Markiewicz Pawel , Marne Paula , Marquié Marta , Martín Elvira , Martínez Joan , Martinez Lage Pablo , Mastenbroek Sophie E. , Maureille Aurélien , Meersmans Karen , Mett Anja , Milne Joseph , Minguillón Carolina , Modat Marc , Molinuevo José Luis , Montrreal Laura , Moro Christian , Müller Theresa , Muniz Graciela , Mutsarts Henk Jan , Nilsson Ted , Ninerola Aida , Nordberg Agneta , Novaes Wilse , Nuno Carmelo Pires Silva Joao , Operto Greg , Orellana Adela , Ousset Pierre-Jean , Outteryck Olivier , Pallardy Amandine , Palombit Alessandro , Pancho Ana , Pappon Martin , Paquet Claire , Pariente Jérémie , Pasquier Florence , Payoux Pierre , Peaker Harry , Pelejà Esther , Pennetier Delphine , Pérez-Cordón Alba , Perissinotti Andrés , Perrenoud Matthieu Paul , Petit Sandrine , Petyt Grégory , Pfeil Julia , Pirotte Blanche , Pla Sandra , Plaza Wuthrich Sonia , Poitrine Lea , Pollet Marianne , Poncelet Jean-Benoit , Prior John , Pruvo Jean-Pierre , Putallaz Pauline , Queneau Mathieu , Quenon  Lisa , Rădoi Andreea , Rafiq Marie , Ramage Fiona , Ramis Maribel , Reinwald Michael , Rios Gonzalo , Ritchie Craig , Rodriguez Elena , Rollin Adeline , Rouaud Olivier , Sacuiu Simona , Saint-Aubert Laure , Sala Arianna , Salabert Anne-Sophie , Saldias Jon , Salvadó Gemma , Sanabria Angela , Sannemann Lena , Sastre Nathalie , Savina Daniela , Savitcheva Irina , Schaeverbeke Jolien , Scheltens Philip , Schildermans Carine , Schmidt Mark , Schöll Michael , Schuermans Jeroen , Semah Franck , Shekari Mahnaz , Skoog Ingmar , Sotolongo-Grau Oscar , Stephens Andrew , Stewart Tiffany , Stutzmann Jennyfer , Tait Murray , Tárraga Lluis , Tartari Juan Pablo , Tysen-backstrom Ann-christine , Valero Sergi , Vallez Garcia David , van Berckel Bart N.M. , van Essen Martijn , Van Laere Koen , van Leur Jeroen , van Maurik Ingrid S. , Vandenberghe Rik , Vellas Bruno , Virolinen Jukka , Visser Pieter Jelle , Walker Zuzana , Walles Håkan , Wallin Emilia , Whitelaw Grant , Wimberley Catriona , Win          Zarni , Wink Alle Meije , Wolz Robin , Woodside John , Yaqub Maqsood , Zettergren Anna , Zeyen Philip 
Published: May 2023

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 &amp;lt; .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P &amp;lt; .001; MCI: 45/108 [42%] vs 9/102 [9%]; P &amp;lt; .001; dementia: 39/80 [49%] vs 16/80 [20%]; P &amp;lt; .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