ArticlesCerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study
Introduction
PET imaging biomarkers such as Pittsburgh compound B (11C-PIB),1 florbetaben (18F),2 flutemetamol (18F),3 and florbetapir (18F)4 provide the potential for in-vivo identification of amyloid-β pathology in patients being assessed for Alzheimer's disease or other causes of cognitive decline. We have shown a strong relation between amyloid-β density estimated from florbetapir PET imaging (with semiquantitative visual interpretation and quantitative standard uptake value ratio [SUVR]) and that assessed by use of immunohistochemistry or silver stain at autopsy.5 Results of other studies with 11C-PIB and flutemetamol have similarly shown associations between amyloid burden estimated by use of PET imaging and amyloid levels at autopsy or after biopsy.6, 7, 8, 9, 10 However, so far, these studies have all been small and their results have not established the sensitivity or specificity of these PET tracers compared with a defined pathology reference standard.
Our previous study5 was designed to continue until 35 autopsy assessments had been obtained. The current study is a continuation of the previous one. Participants who were alive and therefore did not have an autopsy in the original study were followed up to autopsy or for an additional year (maximum of 2 years) after the PET scan. Images and histopathological results from the original and extended follow-up were analysed together to test the sensitivity and specificity of a binary visual interpretation (ie, amyloid positive or amyloid negative) of florbetapir PET scans by comparison with the reference standard of neuritic plaque density at autopsy. We also aimed to confirm, in this larger population, the correlation previously noted between the PET scan and a quantitative immunohistochemical assessment of brain amyloid β.
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Participants
Participants with a cognitive status of normal to advanced dementia were enrolled at 22 centres across the USA between February, 2009, and March, 2010, from inpatient and community hospice centres, long-term-care facilities, and outpatient community health-care and memory centres as part of our previous study.5 All participants had a life expectancy of less than 6 months in the opinion of the enrolling physician at entry and no evidence of destructive brain lesions that would interfere with
Results
152 participants (aged 47–103 years) were recruited in the current study.5 In total, 147 valid scans were obtained. Figure 1 shows the flow of individuals in the current study. Five participants were excluded because of invalid (poor-quality) scans (from excessive movement or camera failure). The initial study reached its predefined stopping point after 35 participants died and had an autopsy. The remaining participants were followed up for 1 year thereafter, or to a maximum of 2 years after
Discussion
The results of this study, designed as an extension of our previous study,5 reaffirmed the relation between florbetapir PET and brain amyloid pathology assessed at autopsy. The results also showed agreement between the binary qualitative florbetapir PET scan visual rating (amyloid positive or amyloid negative) and the neuropathological classification (moderate or frequent vs no or sparse neuritic plaques) at autopsy in participants with a range of amyloid-β pathology that is similar to the
References (21)
- et al.
Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism
Lancet Neurol
(2008) - et al.
National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease
Alzheimers Dement
(2012) - et al.
Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging
Neurobiol Aging
(2010) - et al.
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B
Ann Neurol
(2004) - et al.
Whole-body biodistribution and radiation dosimetry of 18F-GE067: a radioligand for in vivo brain amyloid imaging
J Nucl Med
(2009) - et al.
In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18)
J Nucl Med
(2010) - et al.
Use of florbetapir-PET for imaging beta-amyloid pathology
JAMA
(2011) - et al.
Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B
Arch Neurol
(2008) - et al.
In vivo fibrillar beta-amyloid detected using [11C] PiB positron emission tomography and neuropathologic assessment in older adults
Arch Neurol
(2011) - et al.
Multimodality imaging characteristics of dementia with Lewy bodies
Neurobiol Aging
(2011)
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