Journal ArticleDOI
Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study
Henryk Barthel,Hermann-Josef Gertz,Stefan Dresel,Oliver Peters,Peter Bartenstein,Katharina Buerger,Florian Hiemeyer,Sabine M Wittemer-Rump,John Seibyl,Cornelia Reininger,Osama Sabri +10 more
TLDR
The diagnostic efficacy of the scans was established in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection and the sensitivity and specificity of florbetaben (¹⁸F) PET was assessed.Abstract:
Summary Background Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben ( 18 F) is a promising 18 F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben ( 18 F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. Methods We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben ( 18 F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18–26, clinical dementia rating [CDR]=0·5–2·0) and age-matched healthy controls (MMSE ≥28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90–110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. Findings 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71–89) and a specificity of 91% (84–98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p r −0·27 to −0·33, p≤0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65% vs 22% [p=0·027] in patients with Alzheimer's disease; 50% vs 16% [p=0·074] in healthy controls). No safety concerns were noted. Interpretation We provide verification of the efficacy, safety, and biological relevance of florbetaben ( 18 F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Funding Bayer Schering Pharma AG.read more
Citations
More filters
Journal ArticleDOI
Optically Pure Diphenoxy Derivatives as More Flexible Probes for β-Amyloid Plaques.
TL;DR: Two separate enantiomers displayed similar properties in vitro and in vivo, and (S/R)-[(123)I]5 may be potential SPECT probes for recognizing Aβ plaques in AD brains.
Journal ArticleDOI
Biomathematical screening of amyloid radiotracers with clinical usefulness index.
TL;DR: To facilitate radiotracers' development, a screening methodology using a biomathematical model and clinical usefulness index (CUI) was proposed to evaluate radiot Racers' diagnostic capabilities.
Book ChapterDOI
PET Imaging of Dementia
TL;DR: In the daily routine of a positron-emission tomography (PET) center, patients with dementia or questionable dementia caused by neurodegenerative disorders have been examined.
Journal ArticleDOI
Temporal and anatomical distribution of 18F-flutemetamol uptake in canine brain using positron emission tomography
TL;DR: This study provides normal baseline data of 18F-flutemetamol PET that can facilitate an objective diagnosis of cognitive dysfunction syndrome in dogs in future.
Journal ArticleDOI
Asociación entre daños en la sustancia blanca y metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva
TL;DR: Los DSB estan asociados a un descenso del metabolismo de the glucosa cerebral, y hallazgos sugieren that the enfermedad of los pequenos vasos pueden contribuir a the disfuncion cognitiva en pacientes con enferbedad of Alzheimer.
References
More filters
Journal ArticleDOI
“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
A practical method for grading the cognitive state of patients for the clinician
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Journal ArticleDOI
Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.
TL;DR: A nonparametric approach to the analysis of areas under correlated ROC curves is presented, by using the theory on generalized U-statistics to generate an estimated covariance matrix.
Journal ArticleDOI
Neuropathological stageing of Alzheimer-related changes.
Heiko Braak,Eva Braak +1 more
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Journal ArticleDOI
Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain
Nathalie Tzourio-Mazoyer,B. Landeau,D. Papathanassiou,Fabrice Crivello,Octave Etard,Nicolas Delcroix,Bernard Mazoyer,Marc Joliot +7 more
TL;DR: An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute was performed and it is believed that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain.
Related Papers (5)
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more
Use of Florbetapir-PET for Imaging β-Amyloid Pathology
Christopher M. Clark,Julie A. Schneider,Barry J. Bedell,Thomas G. Beach,Warren B. Bilker,Mark A. Mintun,Michael J. Pontecorvo,Franz Hefti,Alan Carpenter,Matthew Flitter,Michael J. Krautkramer,Hank F. Kung,R. Edward Coleman,P. Murali Doraiswamy,Adam S. Fleisher,Marwan N. Sabbagh,Carl H. Sadowsky,Eric M. Reiman,Simone P. Zehntner,Daniel Skovronsky +19 more
Imaging beta-amyloid burden in aging and dementia.
Christopher C. Rowe,Steven Ng,Uwe Ackermann,Sylvia J. Gong,Kerryn E. Pike,Gregory Raymond Savage,Tiffany F. Cowie,Kerryn L Dickinson,Paul Maruff,David Darby,Clare Smith,Michael Woodward,John Merory,Henri Tochon-Danguy,Graeme O'Keefe,William E. Klunk,Chett A Mathis,Julie C. Price,Colin L. Masters,Colin L. Masters,Victor L. Villemagne,Victor L. Villemagne +21 more