Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients
Daniele Altomare, Frederik Barkhof, Camilla Caprioglio, Lyduine E. Collij, Philip Scheltens, Isadora Lopes Alves, Femke H. Bouwman, Johannes Berkhof, Ingrid S. van Maurik, Valentina Garibotto, Christian Moro, Julien Delrieu, Pierre Payoux, Laure Saint‐Aubert, Anne Hitzel, José Luís Molinuevo, Oriol Grau‐Rivera, Juan Domingo Gispert, Alexander Drzezga, Frank Jessen, Philip Zeyen, Agneta Nordberg, Irina Savitcheva, Vesna Jelić, Zuzana Walker, Paul Edison, Jean‐François Démonet, Rossella Gismondi, Gill Farrar, Andrew Stephens, Giovanni B. Frisoni, Carla Abdelnour, Núria Aguilera, Leon Aksman, Emilio Alarcón‐Martín, Montserrat Alegret, Sílvia Alonso-Lana, Daniele Altomare, Pia Haubro Andersen, Majd Arab, Malin Aspö, Ilona Bader, Ilse Bader, Nigel Banton, Frederik Barkhof, Rodrigo Barnes, Dawn Barrie, Mark Battle, Ana Belén Collado, Julie Bellet, Johannes Berkhof, Marine Biger, Cindy Birck, Gérard N. Bischof, Merçé Boada, Ronald Boellaard, Nenad Bogdanović, Ariane Bollack, Stéphanie Bombois, Stefan Borg, Anne Börjesson‐Hanson, Vladimir Boskov, Justine Boutantin, Claire Boutoleau‐Bretonnière, Femke H. Bouwman, Laëtitia Breuilh, Eva Bringman, Baptiste Brunel, Marco Bucci, Christopher Buckley, Mar Buendía, Santi Bullich, Anna Calvet, Laia Cañada, Marta Cañada, Camilla Caprioglio, M. Jorge Cardoso, Jasmine Carlier, Elise Carre, Isabelle Carrié, Pascaline Cassagnaud, E. Cassol, M. Castilla, Elodie Cazalon, Tiphaine Chaarriau, Rachel Chaigeau, T. M. Chalmers, Marie-Thérèse Clerc, Montserrat Clerigué, Emmanuel Cognat, Nina Coll, Lyduine E. Collij, Peter Connely, Elodie Cordier, Corine Costes, Camille Coulange, Hélène Courtemanche, E. Creisson, C. Crinquette, Rosario Cuevas
Abstract
Importance: Amyloid 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. Objective: To assess the clinical effect of amyloid PET in memory clinic patients. Design, Setting, and Participants: The 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. Intervention: Amyloid PET. Main Outcome and Measure: The 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. Results: A 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 Relevance: In 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 Registration: EudraCT Number: 2017-002527-21.