Clinical effect of early vs late amyloid positron emission tomography in memory clinic patients: the amypad-dpms randomized clinical trial

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  • dc.contributor.author Altomare, Daniele
  • dc.contributor.author Grau-Rivera, Oriol
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Consortium
  • dc.date.accessioned 2024-03-08T07:05:48Z
  • dc.date.available 2024-03-08T07:05:48Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship The Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) project is funded by the EU European Federation of Pharmaceutical Industries and Associations (EFPIA) Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) (grant agreement 115952). IMI 2 JU aims to advance the development of medicines by facilitating open collaboration on research. To do that, it has funded collaborative research projects that bring together all the parties involved in health research, including universities and pharmaceutical companies. Specifically, the AMYPAD consortium consists of several academic partners and 3 pharmaceutical companies (Life Molecular Imaging, GE Healthcare, and Janssen). Dr Altomare received funding from the Fondation Recherche Alzheimer and Swiss National Science Foundation (project CRSK-3_196354 / 1). Dr Barkhof is supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at University College London Hospitals. Dr Berkhof is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (73305095007) and Health Holland, Top Sector Life Sciences & Health (PPP-allowance; LSHM20106), and received funding from the European Union (AMYPAD, RISCC), ZonMW (HPV compare), WHO, IARC, and RIVM. Ms Caprioglio was supported by the EU-EFPIA IMI 2 JU AMYPAD. Dr van Maurik is recipient of the collaboration project ABIDE-clinical utility, which is co-funded by the PPP Allowance made available by Health Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships and Life Molecular Imaging (grant LSHM18075). Dr Garibotto was supported by the Swiss National Science Foundation (projects 320030_169876, 320030_185028 and IZSEZ0_188355), Velux Foundation (project 1123), Schmidheiny Foundation, and Aetas Foundation. Dr Grau-Rivera received funding from the Alzheimer’s Association (2019-AARF-644568) and Instituto de Salud Carlos III (PI19/00117). Dr Gispert is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054) and received funding from the EU-EFPIA IMI 2 JU AMYPAD. Dr Drzezga received funding from AMYPAD, Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), Europäischen Fonds für regionale Entwicklung (EFRE)/Leitmarkt, University of Cologne, and Forschungszentrum Jülich (Novartis clinical trial). Dr Jessen received funding from the BMBF, DFG, H2020, and IMI. Dr Nordberg received funding from AMYPAD, Swedish Foundation for Strategic Research (RB12-01929), Swedish Research Council (2017-06086, 2017-02965, 2020-019909, CIMED, Swedish Brain Foundation, Swedish Alzheimer Foundation, Recherche Sur Alzheimer Fondation, France, and Michael J. Fox Foundation (MJFF-019728). Dr Walker received funding from Health Technology Assessment NIHR, Lewy Body Society, and ARUK. Dr Edison was funded by the Medical Research Council and now by the Higher Education Funding Council for England (HEFCE). Dr Demonet received funding from the Biogen EMBARK study, Empiris Foundation, Solis Foundation, OM Pharma, and Leenaards Foundation. Dr Frisoni received funding from the EU-EFPIA IMI 2 JU European Prevention of Alzheimer’s Dementia consortium (grant agreement 115736) and AMYPAD; the Swiss National Science Foundation (COSCODE, grant 320030_182772); Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Fondazione Agusta, Lugano; Fondation Chmielewski, Genève; and Velux Foundation. The Geneva Memory Center is funded by the following private donors under the supervision of the Private Foundation of Geneva University Hospitals: Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Fondazione Agusta, Lugano; and Fondation Chmielewski, Genève. Competitive research projects have been funded by H2020, Human Brain Project, IMI and IMI 2, Swiss National Science Foundation, and Velux Foundation. The Barcelonaβeta Brain Research Center memory center received funding from the Barcelona City Council (agreement 20XC0354) and Biogen.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Altomare D, Barkhof F, Caprioglio C, Collij LE, Scheltens P, Lopes Alves I et al. Clinical effect of early vs late amyloid positron emission tomography in memory clinic patients: the amypad-dpms randomized clinical trial. JAMA Neurol. 2023 Jun 1;80(6):548-57. DOI: 10.1001/jamaneurol.2023.0997
  • dc.identifier.doi http://dx.doi.org/10.1001/jamaneurol.2023.0997
  • dc.identifier.issn 2168-6149
  • dc.identifier.uri http://hdl.handle.net/10230/59355
  • dc.language.iso eng
  • dc.publisher American Medical Association
  • dc.relation.ispartof JAMA Neurol. 2023 Jun 1;80(6):548-57
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115736
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
  • dc.rights © 2023 Altomare D et al. JAMA Neurology. This is an open access article distributed under the terms of the CC-BY License (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Tomografia
  • dc.subject.other Alzheimer, Malaltia d'
  • dc.title Clinical effect of early vs late amyloid positron emission tomography in memory clinic patients: the amypad-dpms randomized clinical trial
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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