Performance Characteristics of Amyloid PET with Florbetapir F 18 in Patients with Alzheimer's Disease and Cognitively Normal Subjects
Abhinay D. Joshi,Michael J. Pontecorvo,Chrisopher M. Clark,Alan Carpenter,Danna Jennings,Carl H. Sadowsky,Lee P. Adler,Karel D. Kovnat,John Seibyl,Anupa Arora,Krishnendu Saha,Jason Burns,Mark J. Lowrey,Mark A. Mintun,Daniel Skovronsky +14 more
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TLDR
Florbetapir F 18 appears to have a wide effective dose range and a high test–retest reliability for both quantitative (SUVr) values and visual assessment of the ligand, and these imaging performance properties provide important technical information on the use of florbetapIR F 18 and PET to detect cerebral amyloid aggregates.Abstract:
The objectives of this study were to examine the effective dose range and the test–retest reliability of florbetapir F 18 using, first, visual assessment by independent raters masked to clinical information and, second, semiautomated quantitative measures of cortical target area to cerebellum standardized uptake value ratios (SUVr) as primary outcome measures. Visual ratings of PET image quality and tracer retention or b-amyloid (Ab) binding expressed as SUVrs were compared after intravenous administration of either 111 MBq (3 mCi) or 370 MBq (10 mCi) of florbetapir F 18 in patients with Alzheimer’s disease (AD) (n 5 9) and younger healthy controls (YHCs) (n 5 11). In a separate set of subjects (AD, n 5 10; YHCs, n 5 10), test–retest reliability was evaluated by comparing intrasubject visual read ratings and SUVrs for 2 PET images acquired within 4 wk of each other. Results: There were no meaningful differences between the 111-MBq (3-mCi) and 370-MBq (10-mCi) dose in the visual rating or SUVr. The difference in the visual quality across 111 and 370 MBq showed a trend toward lower image quality, but no statistical significance was achieved (t test; t1 52 1.617, P 5 0.12) in this relatively small sample of subjects. At both dose levels, visual ratings of amyloid burden identified 100% of AD subjects as Ab-positive and 100% of YHCs as Ab-negative. Mean intrasubject test–retest variability for cortical average SUVrs with the cerebellum as a reference over the 50- to 70-min period was 2.4% 6 1.41% for AD subjects and 1.5% 6 0.84% for controls. The overall SUVr test–retest correlation coefficient was 0.99. The overall k-statistic for test–retest agreement for Ab classification of the masked reads was 0.89 (95% confidence interval, 0.69–1.0). Conclusion: Florbetapir F 18 appears to have a wide effective dose range and a high test– retest reliability for both quantitative (SUVr) values and visual assessment of the ligand. These imaging performance properties provide important technical information on the use of florbetapir F 18 and PET to detect cerebral amyloid aggregates.read more
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Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Bruno Dubois,Bruno Dubois,Howard Feldman,Claudia Jacova,Harald Hampel,Harald Hampel,José Luis Molinuevo,Kaj Blennow,Steven T. DeKosky,Serge Gauthier,Dennis J. Selkoe,Randall J. Bateman,Stefano F. Cappa,Sebastian J. Crutch,Sebastiaan Engelborghs,Giovanni B. Frisoni,Nick C. Fox,Douglas Galasko,Marie-Odile Habert,Gregory A. Jicha,Agneta Nordberg,Florence Pasquier,Gil D. Rabinovici,Philippe Robert,Christopher C. Rowe,Stephen Salloway,Marie Sarazin,Stéphane Epelbaum,Stéphane Epelbaum,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Bruno Vellas,Pieter Jelle Visser,Lon S. Schneider,Yaakov Stern,Philip Scheltens,Jeffrey L. Cummings +37 more
TL;DR: It is proposed that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease.
Journal ArticleDOI
Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study
Christopher M. Clark,Michael J. Pontecorvo,Thomas G. Beach,Barry J. Bedell,R. Edward Coleman,P. Murali Doraiswamy,Adam S. Fleisher,Eric M. Reiman,Marwan N. Sabbagh,Carl H. Sadowsky,Julie A. Schneider,Anupa Arora,Alan Carpenter,Matthew Flitter,Abhinay D. Joshi,Michael J. Krautkramer,Ming Lu,Mark A. Mintun,Daniel Skovronsky +18 more
TL;DR: The results of this study validate the binary visual reading method approved in the USA for clinical use with flor betapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques.
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Amyloid deposition, hypometabolism, and longitudinal cognitive decline.
Susan M. Landau,Mark A. Mintun,Abhinay Joshi,Robert A. Koeppe,Ronald C. Petersen,Paul S. Aisen,Michael W. Weiner,William J. Jagust,William J. Jagust +8 more
TL;DR: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, cross‐sectional relationships between amyloid deposition, hypometabolism, and cognition are examined.
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Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.
Rebecca F. Gottesman,Rebecca F. Gottesman,Andrea L.C. Schneider,Yun Zhou,Josef Coresh,Edward D Green,Naresh Gupta,David S. Knopman,Akiva Mintz,Arman Rahmim,A. Richey Sharrett,Lynne E. Wagenknecht,Dean F. Wong,Thomas H. Mosley +13 more
TL;DR: An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors.
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Cascading network failure across the Alzheimer's disease spectrum.
David T.W. Jones,David S. Knopman,Jeffrey L. Gunter,Jonathan Graff-Radford,Prashanthi Vemuri,Bradley F. Boeve,Ronald C. Petersen,Michael W. Weiner,Clifford R. Jack +8 more
TL;DR: An in-depth analysis of changes within subsystems within the default mode network are related to biomarker profiles across the Alzheimer’s disease spectrum and results support a cascading network failure model of Alzheimer's disease.
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