Use of Flutemetamol F 18–Labeled Positron Emission Tomography and Other Biomarkers to Assess Risk of Clinical Progression in Patients With Amnestic Mild Cognitive Impairment

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.

Is there a difference in regional read [18F]flutemetamol amyloid patterns between end-of-life subjects and those with amnestic mild cognitive impairment?

“… More comprehensive study details can be found in Wolk et al [ 11 ] CAC Clinical Adjudication Committee a Of those reviewed by the CAC …”

“…The aMCI patients were, on average, 10 years younger than the EoL patients (mean age 71 years, range 53–91 years) and comprised 232 patients who took part in a 3-year follow-up study to determine whether a positive [ 18 F]flutemetamol PET scan or positivity using other biomarkers would increase the risk of progression to AD (Table 2 ). The demographics and inclusion criteria for this study have been described by Wolk et al [ 11 ]. Of the 232 aMCI patients, 224 were reviewed by a Clinical Adjudication Committee (CAC) to assess conversion status [ 11 ].…”

“…The demographics and inclusion criteria for this study have been described by Wolk et al [ 11 ]. Of the 232 aMCI patients, 224 were reviewed by a Clinical Adjudication Committee (CAC) to assess conversion status [ 11 ]. Of the 224 aMCI patients with evaluable images, 97 showed a positive read (i.e.…”

Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment

“…detecting amyloid pathology later confirmed at post-mortem (Ikonomovic et al, 2016;Sabri et al, 2015;Thal et al, 2015), comparable diagnostic utility to [ 11 C]PiB (Lowe et al, 2017;Villemagne et al, 2012), effectiveness in the prediction of conversion from MCI to AD (Ong et al, 2015;Wolk et al, 2018), and the clinical benefit of increased dementia diagnostic confidence (Schipke et al, 2012;Zwan et al, 2017). Associations are shown between Aβ uptake and cognitive dysfunction in AD (Barthel et al, 2011) and MCI (Bahar-Fuchs et al, 2013) for [ 18 F]florbetaben.…”

“…When considering the clinical implementation of this modality, recent evidence demonstrates its cost-effectiveness(Hornberger, Bae, Watson, Johnston, & Happich, 2017) and meaningful impact on the diagnostic confidence for AD by physicians(Boccardi et al, 2016).While not as widely investigated as [ 18 F]florbetapir, a similar pattern of amyloid retention is demonstrated throughout the cortex in AD using both [ 18 F]florbetaben(Barthel et al, 2011) and [ 18 F] flutemetamol(Nelissen et al, 2009). Additional commonalities shared by these two tracers with [ 18 F]florbetapir include high rates of sensitivity and specificity in diagnosing AD(Barthel et al, 2011;Hatashita et al, 2014;Rowe et al, 2008;Tiepolt et al, 2013;Vandenberghe et al, 2010;Villemagne et al, 2011) and detecting amyloid pathology later confirmed at post-mortem(Ikonomovic et al, 2016;Sabri et al, 2015;Thal et al, 2015), comparable diagnostic utility to [ 11 C]PiB(Lowe et al, 2017;Villemagne et al, 2012), effectiveness in the prediction of conversion from MCI to AD(Ong et al, 2015;Wolk et al, 2018), and the clinical benefit of increased dementia diagnostic confidence(Schipke et al, 2012;Zwan et al, 2017). Additional commonalities shared by these two tracers with [ 18 F]florbetapir include high rates of sensitivity and specificity in diagnosing AD(Barthel et al, 2011;Hatashita et al, 2014;Rowe et al, 2008;Tiepolt et al, 2013;Vandenberghe et al, 2010;Villemagne et al, 2011) and detecting amyloid pathology later confirmed at post-mortem(Ikonomovic et al, 2016;Sabri et al, 2015;Thal et al, 2015), comparable diagnostic utility to [ 11 C]PiB(Lowe et al, 2017;Villemagne et al, 2012), effectiveness in the prediction of conversion from MCI to AD(Ong...…”