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Background: Amyloid-β (Aβ) accumulation is considered the earliest pathological change in Alzheimer’s disease (AD). The Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) consortium is a collaborative European framework across European Federation of Pharmaceutical Industries Associations (EFPIA), academic, and ‘Small and Medium-sized enterprises’ (SME) partners aiming to provide evidence on the clinical utility and cost-effectiveness of Positron Emission Tomography (PET) imaging in diagnostic work-up of AD and to support clinical trial design by developing optimal quantitative methodology in an early AD population. The AMYPAD studies: In the Diagnostic and Patient Management Study (DPMS), 844 participants from eight centres across three clinical subgroups (245 subjective cognitive decline, 342 mild cognitive impairment, and 258 dementia) were included. The Prognostic and Natural History Study (PNHS) recruited pre-dementia subjects across 11 European parent cohorts (PCs). Approximately 1600 unique subjects with historical and prospective data were collected within this study. PET acquisition with [18F]flutemetamol or [18F]florbetaben radiotracers was performed and quantified using the Centiloid (CL) method. Results: AMYPAD has significantly contributed to the AD field by furthering our understanding of amyloid deposition in the brain and the optimal methodology to measure this process. Main contributions so far include the validation of the dual-time window acquisition protocol to derive the fully quantitative non-displaceable binding potential (BPND), assess the value of this metric in the context of clinical trials, improve PET-sensitivity to emerging Aβ burden and utilize its available regional information, establish the quantitative accuracy of the Centiloid method across tracers and support implementation of quantitative amyloid-PET measures in the clinical routine. Future steps: The AMYPAD consortium has succeeded in recruiting and following a large number of prospective subjects and setting up a collaborative framework to integrate data across European PCs. Efforts are currently ongoing in collaboration with ARIDHIA and ADDI to harmonize, integrate, and curate all available clinical data from the PNHS PCs, which will become openly accessible to the wider scientific community.

Importance Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. Objective To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. Design, Setting, and Participants This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. Exposures Disclosure of amyloid-PET result. Main Outcomes and Measures Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale–Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). Results After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P P P P P = .06) and Depression (–1.0 [–2.0 to 0.0] vs –1.0 [–3.0 to 0.0]; P = .46) deltas (score after disclosure – scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = –0.43; P = .02) whereas the presence of study partner was associated with higher disclosure-related distress (W = 7.5; P = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. Conclusions and Relevance The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.

Introduction Reimbursement of amyloid–positron emission tomography (PET) is lagging due to the lack of definitive evidence on its clinical utility and cost-effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease–Diagnostic and Patient Management Study (AMYPAD-DPMS) is designed to fill this gap. Methods AMYPAD-DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid-PET performed early in the diagnostic workup; ARM2, amyloid-PET performed after 8 months; and ARM3, amyloid-PET performed whenever the physician chooses to do so. Endpoints The primary endpoint is the difference between ARM1 and ARM2 in the proportion of patients receiving a very-high-confidence etiologic diagnosis after 3 months. Secondary endpoints address diagnosis and diagnostic confidence, diagnostic/therapeutic management, health economics and patient-related outcomes, and methods for image quantitation. Expected Impacts AMYPAD-DPMS will supply physicians and health care payers with real-world data to plan management decisions.

Introduction:Reimbursement of amyloid-positron emission tomography (PET) is lagging due to the lack of definitive evidence on its clinical utility and cost-effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease-Diagnostic and Patient Management Study (AMYPAD-DPMS) is designed to fill this gap. Methods:AMYPAD-DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid-PET performed early in the diagnostic workup; ARM2, amyloid-PET performed after 8 months; and ARM3, amyloid-PET performed whenever the physician chooses to do so. Endpoints:The primary endpoint is the difference between ARM1 and ARM2 in the proportion of patients receiving a very-high-confidence etiologic diagnosis after 3 months. Secondary endpoints address diagnosis and diagnostic confidence, diagnostic/therapeutic management, health economics and patient-related outcomes, and methods for image quantitation. Expected impacts:AMYPAD-DPMS will supply physicians and health care payers with real-world data to plan management decisions. Keywords:Alzheimer's disease; Amyloid-PET; Clinical validity; Cost-effectiveness; Mild cognitive impairment; Subjective cognitive decline.

Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.

Introduction La maladie d’Alzheimer (MA) est de diagnostic difficile, en particulier dans ses formes precoces et atypiques, ou cas de comorbidites. Dans ce contexte, l’analyse des biomarqueurs du Liquide Cephalo-Rachidien (LCR) est recommandee, mais reste non realisable ou non-conclusive chez certains patients. Cette etude s’est interessee a l’impact de la TEP amyloide au 18F-Florbetaben sur le diagnostic et la prise en charge de ce groupe particulier de patients. Materiels & methodes Cette etude multicentrique (ClinicalTrials.gov : NCT02681172 ) a ete realisee au sein de 19 CMRR (Centre Memoire de Ressources et de Recherche), et services de Medecine Nucleaire associes. Elle incluait les patients eligibles pour une analyse des biomarqueurs du LCR en reference aux recommandations formulees par la Haute Autorite de sante (HAS), mais pour lesquels la ponction lombaire (PL) etait non realisable (contre-indication ; refus) ou pour lesquels les resultats etaient consideres comme ambigus. La TEP amyloide au 18F-Florbetaben etait realisee localement aupres de medecins nucleaires formes a l’interpretation de ces images. Apres diffusion du compte-rendu, le diagnostic retenu et la prise en charge etaient compares a l’evaluation initiale realisee avant la TEP. Resultats Cette etude incluait au final 205 patients (103 hommes ; 70,9 ans ± 9,7) avec un examen TEP realise et interpretable. Parmi eux, 118 n’avaient pas eu de PL, avec un refus pour 75 de ces cas. Au total, 132 des 205 examens (64,4 %) etaient positifs (amyloide + ). Apres diffusion des resultats des examens, 137/205 des diagnostics initiaux (66,8 %) etaient modifies, plus particulierement encore en cas de resultats negatifs (83,6 % vs. 57,6 % en cas d’amyloide + ; p p Conclusion L’interpretation visuelle de la TEP amyloide au 18F-Florbetaben conduite localement par des medecins nucleaires formes a ces examens influence les decisions d’expertise clinique chez les patients pour qui la PL n’est pas realisable ou pour qui les resultats du LCR restent ambigus. Ces resultats encouragent l’integration de la TEP amyloide au schema d’expertise de prise en charge diagnostique de la MA. Financement : Piramal Imaging.