Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

Ong, Kevin; Villemagne, Victor L.; Bahar‐Fuchs, Alex; Lamb, Fiona; Langdon, Narelle; Catafau, Ana M.; Stephens, Andrew; Seibyl, John; Dinkelborg, Ludger; Reininger, Cornelia; Pütz, Barbara; Rohde, Beate; Masters, Colin L.; Rowe, Christopher C.

doi:10.1136/jnnp-2014-308094

Cited by 83 publications

(79 citation statements)

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“…However, potential subtle changes in Ab burden over time may not be apparent by visual inspection of the images. Thus, quantitative analysis has been found necessary for longitudinal observational studies and interventional trials when a change in amyloid burden measured by PET serves as a treatment endpoint (4,5).…”

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confidence: 99%

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

et al. 2016

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SUV ratios (SUVRs) are used for relative quantification of 18 Fflorbetaben scans. The cerebellar cortex can be used as a reference region for quantification. However, cerebellar amyloid-β (Aβ) plaques may be present in Alzheimer disease (AD). The aim of this study was to assess the influence of Aβ pathology, including neuritic plaques, diffuse plaques, and vascular deposits, in 18 F-florbetaben SUVR when cerebellum is used as the reference. Methods: Using immunohistochemistry to demonstrate Aβ plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age ± SD, 80.4 ± 10.2 y) who had undergone 18 F-florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Aβ loads. Results: None of the 83 evaluable cerebellar samples showed frequent diffuse Aβ or neuritic plaques; 8 samples showed frequent vascular Aβ deposits. Diffuse Aβ plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Aβ was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Aβ deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26-44 cases. No significant SUVR differences were found between these brains with different cerebellar Aβ loads. Conclusion: The effect of cerebellar plaques on cortical 18 F-florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Aβ load.

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confidence: 99%

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

et al. 2016

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“…44 Some studies satisfied both NINCDS-ADRDA and DSM-IV criteria, 22,23,[26][27][28]31,38 and others used only one set of criteria. Some studies that used NINCDS-ADRDA criteria adopted probable AD, 10,12,14,17,[19][20][21]23,[26][27][28][29]32,33 whereas other studies did not indicate the diagnosis as probable or possible AD. Our study excluded other types of dementia, not AD.…”

Section: Discussionmentioning

confidence: 99%

“…3,17,19,27,[29][30][31][32]43 Two studies included in this meta-analysis assessed hippocampus volume by MRI and amyloid burden by PET in the same patients. 29,32 These studies reported higher odds ratios/positive predictive value/negative predictive value/accuracy for amyloid PET than MRI hippocampus volume reduction on MRI. Another European collaborative study predicted conversion to AD in patients with MCI using CSF Aβ42 concentration, cortical metabolism by FDG-PET, and MRI hippocampus atrophy.…”

Section: Discussionmentioning

confidence: 99%

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P1‐149: Structural MRI and amyloid PET imaging for prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment: A meta‐analysis

Park

Kim

Park

et al. 2015

Alzheimer's & Dementia

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Alzheimer's disease (AD) has an insidious onset with a slowly progressive course. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal and AD. In particular, amnestic MCI is considered as a prodromal stage of AD. MCI may therefore be a target for the prediction of who will develop AD prediction. Several markers during the prodromal MCI stage, including neuropsychological tests, have been proposed for the prediction of AD. However, no Print ISSN 1738-3684 / On-line ISSN 1976 OPEN ACCESS Copyright © 2017 Korean Neuropsychiatric Association 205single study has included enough data to provide a reliable predictor of AD. The International Working Group (IWG) and National Institute on Aging Alzheimer's Association (NIA-AA) has proposed several biomarkers as diagnostic criteria for MCI, including cerebro spinal fluid (CSF) amyloid beta (Aβ) and tau, atrophy on MRI, glucose metabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and fibrillar Aβ burden on amyloid PET. 1,2 FDG-PET has been suggested to be the strongest predictor for progression from MCI to AD, 3 however, its high costs may limit its widespread adoption. A CSF assessment requires a lumbar puncture, which is regarded an invasive procedure, although it is widely implemented without problems in the elderly. In contrast, MRI is noninvasive, widely used in clinical settings and also could be easily performed. Atrophy measurements on MRI have been used to predict the progression to AD inpatients with MCI since the 1990s. Most studies have

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“…This suggests that accumulation of Aβ plateaus while hippocampal volume continues to decrease. Therefore, over time, hippocampal atrophy and not accumulation of Aβ facilitates dementia progression [44].…”

Section: [ 18 F]-av-1 or [F-18]-bay94-9172 Or Florbetabenmentioning

confidence: 99%

Amyloid Imaging: Poised for Integration into Medical Practice

Anand

Sabbagh

2017

Neurotherapeutics

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Amyloid imaging represents a significant advance as an adjunct in the diagnosis of Alzheimer's disease (AD) because it is the first imaging modality that identifies in vivo changes known to be associated with the pathogenesis. Initially, 11 C-PIB was developed, which was the prototype for many 18 F compounds, including florbetapir, florbetaben, and flutemetamol, among others. Despite the high sensitivity and specificity of amyloid imaging, it is not commonly used in clinical practice, mainly because it is not reimbursed under current Center for Medicare and Medicaid Services guidelines in the USA. To guide the field in who would be most appropriate for the utility of amyloid positron emission tomography, current studies are underway [Imaging Dementia Evidence for Amyloid Scanning (IDEAS) Study] that will inform the field on the utilization of amyloid positron emission tomography in clinical practice. With the advent of monoclonal antibodies that specifically target amyloid antibody, there is an interest, possibly a mandate, to screen potential treatment recipients to ensure that they are suitable for treatment. In this review, we summarize progress in the field to date.

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Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

Abstract: NCT01138111.

Cited by 83 publications

References 36 publications

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

P1‐149: Structural MRI and amyloid PET imaging for prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment: A meta‐analysis

Amyloid Imaging: Poised for Integration into Medical Practice

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Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

Abstract: NCT01138111.

Cited by 83 publications

References 36 publications

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence 18F-Florbetaben SUV Ratios?

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence 18F-Florbetaben SUV Ratios?

P1‐149: Structural MRI and amyloid PET imaging for prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment: A meta‐analysis

Amyloid Imaging: Poised for Integration into Medical Practice

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Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?

Cerebellar Amyloid-β Plaques: How Frequent Are They, and Do They Influence ¹⁸F-Florbetaben SUV Ratios?