Use of flutemetamol F18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment

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Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. Objective: To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. Design, Setting, and Participants: In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018. Interventions: Flutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures. Main Outcomes and Measures: Time from PET to probable AD or last follow-upwas plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD. Results: Of 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6%(52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive β-amyloid scan alone (primary outcome measure), 5.60 (95%CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95%CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model. Conclusions and Relevance: A combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.


  • David A. Wolk
  • Carl Sadowsky
  • Beth Safirstein
  • Juha O. Rinne
  • Ranjan Duara
  • Richard Perry
  • Marc Agronin
  • Jose Gamez
  • Jiong Shi
  • Adrian Ivanoiu
  • Zuzana Walker
  • Steen Hasselbalch
  • Clive Holmes
  • Marwan Sabbagh
  • Marilyn Albert
  • Adam Fleisher
  • Paul Loughlin
  • Eric Triau
  • Kirk Frey
  • Peter Høgh
  • Andrea Bozoki
  • Roger Bullock
  • Eric Salmon
  • Gillian Farrar
  • Christopher J. Buckley
  • Michelle Zanette
  • Paul F. Sherwin
  • Andrea Cherubini
  • Fraser Inglis
External organisations
  • University of Pennsylvania
  • Nova Southeastern University
  • Turku University Hospital
  • Charing Cross Hospital
  • Miami Jewish Health Systems
  • Galiz Research
  • Saint-Luc University Hospital
  • University College London
  • Essex Partnership University Foundation Trust Essex
  • University of Copenhagen
  • Moorgreen Hospital
  • University of Southampton
  • Banner Sun Health Research Institute
  • Banner Alzheimer's Institute
  • Lilly Research Laboratories
  • Princess Margaret Hospital, Windsor
  • Copenhagen University Hospital
  • Michigan State University
  • Kingshill Research Centre
  • University of Liège
  • GE Healthcare, UK
  • CNR Institute of Molecular Bioimaging and Physiology, Italy (IBFM-CNR)
  • Glasgow Memory Clinic Ltd.
  • MD Clinical, Hallandale Beach
  • University of Turku
  • Mount Sinai Medical Center, Miami Beach
  • Imperial College London
  • St. Joseph's Hospital and Medical Center
  • Johns Hopkins University
  • No affiliation available (private)
  • University of Michigan
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Pages (from-to)1114-1123
Number of pages10
JournalJAMA Neurology
Issue number9
Publication statusPublished - 2018
Publication categoryResearch