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

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

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.

2168-6149
1114-1123
Wolk, David A.
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Sadowsky, Carl
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Safirstein, Beth
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Rinne, Juha O.
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Duara, Ranjan
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Perry, Richard
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Agronin, Marc
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Gamez, Jose
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Shi, Jiong
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Ivanoiu, Adrian
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Minthon, Lennart
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Walker, Zuzana
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Holmes, Clive
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Fleisher, Adam
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Frey, Kirk
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Høgh, Peter
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Bozoki, Andrea
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Bullock, Roger
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Salmon, Eric
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Farrar, Gillian
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Buckley, Christopher J.
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Zanette, Michelle
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Sherwin, Paul F.
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Cherubini, Andrea
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Inglis, Fraser
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Wolk, David A.
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Sadowsky, Carl
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Duara, Ranjan
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Perry, Richard
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Agronin, Marc
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Gamez, Jose
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Shi, Jiong
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Ivanoiu, Adrian
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Minthon, Lennart
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Walker, Zuzana
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Hasselbalch, Steen
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Frey, Kirk
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Høgh, Peter
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Bozoki, Andrea
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Bullock, Roger
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Salmon, Eric
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Farrar, Gillian
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Buckley, Christopher J.
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Zanette, Michelle
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Sherwin, Paul F.
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Cherubini, Andrea
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Inglis, Fraser
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Wolk, David A., Sadowsky, Carl, Safirstein, Beth, Rinne, Juha O., Duara, Ranjan, Perry, Richard, Agronin, Marc, Gamez, Jose, Shi, Jiong, Ivanoiu, Adrian, Minthon, Lennart, Walker, Zuzana, Hasselbalch, Steen, Holmes, Clive, Sabbagh, Marwan, Albert, Marilyn, Fleisher, Adam, Loughlin, Paul, Triau, Eric, Frey, Kirk, Høgh, Peter, Bozoki, Andrea, Bullock, Roger, Salmon, Eric, Farrar, Gillian, Buckley, Christopher J., Zanette, Michelle, Sherwin, Paul F., Cherubini, Andrea and Inglis, Fraser (2018) Use of flutemetamol F18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment. JAMA Neurology, 75 (9), 1114-1123. (doi:10.1001/jamaneurol.2018.0894).

Record type: Article

Abstract

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.

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Accepted/In Press date: 16 February 2018
e-pub ahead of print date: 14 May 2018
Published date: 1 September 2018

Identifiers

Local EPrints ID: 423618
URI: http://eprints.soton.ac.uk/id/eprint/423618
ISSN: 2168-6149
PURE UUID: ec6d5d9b-f697-45af-bc68-ad3146b480d1
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

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Date deposited: 27 Sep 2018 16:30
Last modified: 18 Feb 2021 16:53

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Contributors

Author: David A. Wolk
Author: Carl Sadowsky
Author: Beth Safirstein
Author: Juha O. Rinne
Author: Ranjan Duara
Author: Richard Perry
Author: Marc Agronin
Author: Jose Gamez
Author: Jiong Shi
Author: Adrian Ivanoiu
Author: Lennart Minthon
Author: Zuzana Walker
Author: Steen Hasselbalch
Author: Clive Holmes ORCID iD
Author: Marwan Sabbagh
Author: Marilyn Albert
Author: Adam Fleisher
Author: Paul Loughlin
Author: Eric Triau
Author: Kirk Frey
Author: Peter Høgh
Author: Andrea Bozoki
Author: Roger Bullock
Author: Eric Salmon
Author: Gillian Farrar
Author: Christopher J. Buckley
Author: Michelle Zanette
Author: Paul F. Sherwin
Author: Andrea Cherubini
Author: Fraser Inglis

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