title: Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study.
abstract: BACKGROUND
  We assessed the clinical utility of β-amyloid (Aβ) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.
  
  
  METHODS
  45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <-1.5.
  
  
  RESULTS
  At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-.
  
  
  CONCLUSIONS
  (18)F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.
  
  
  BACKGROUND
  NCT01138111.
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors: Kevin T
authors: KT
authors: Ong
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors: Victor L
authors: VL
authors: Villemagne
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia Centre for Research on Aging, Health, and Wellbeing, The Australian National University, Acton, Australian Capital Territory, Australia.
authors: Alex
authors: A
authors: Bahar-Fuchs
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors: Fiona
authors: F
authors: Lamb
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors: Narelle
authors: N
authors: Langdon
authors: Piramal Imaging GmbH, Berlin, Germany.
authors: Ana M
authors: AM
authors: Catafau
authors: Piramal Imaging GmbH, Berlin, Germany.
authors: Andrew W
authors: AW
authors: Stephens
authors: Molecular NeuroImaging, L.L.C., New Haven, Connecticut, USA.
authors: John
authors: J
authors: Seibyl
authors: Piramal Imaging GmbH, Berlin, Germany.
authors: Ludger M
authors: LM
authors: Dinkelborg
authors: Bayer Healthcare, Berlin, Germany.
authors: Cornelia B
authors: CB
authors: Reininger
authors: Bayer Healthcare, Berlin, Germany.
authors: Barbara
authors: B
authors: Putz
authors: Bayer Healthcare, Berlin, Germany.
authors: Beate
authors: B
authors: Rohde
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors: Colin L
authors: CL
authors: Masters
authors: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors: Christopher C
authors: CC
authors: Rowe
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D013267:Stilbenes
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
keywords: ALZHEIMER'S DISEASE; AMYLOID; COGNITION; DEMENTIA; MRI