| 1. |
- Adamczuk, Katarzyna, et al.
(författare)
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Amyloid imaging in cognitively normal older adults : comparison between F-18-flutemetamol and C-11-Pittsburgh compound B
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:1, s. 142-151
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: F-18-flutemetamol and C-11-Pittsburgh compound B (PIB). Methods In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on F-18-flutemetamol versus C-11-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between F-18-flutemetamol and C-11-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Results Binary classification based on semiquantitative assessment was concordant between F-18-flutemetamol and C-11-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between F-18-flutemetamol and C-11-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. Conclusion For the definition of preclinical AD based on F-18-flutemetamol, concordance with C-11-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
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| 2. |
- Adamczuk, Katarzyna, et al.
(författare)
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Diagnostic value of cerebrospinal fluid A beta ratios in preclinical Alzheimer's disease
- 2015
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) A beta ratios rather than A beta 42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). Methods: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent F-18-flutemetamol PET and CSF measurement of A beta 1-42, A beta 1-40, A beta 1-38, and total tau (ttau). F-18-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and F-18-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. Results: Seven out of 38 subjects (18 %) were positive on amyloid PET. A beta 42/ttau, A beta 42/A beta 40, A beta 42/A beta 38, and A beta 42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) >= 0.908). A beta 40 and A beta 38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, A beta 42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of A beta 42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). Conclusion: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of A beta 42/ttau rather than using A beta 42 in isolation.
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| 3. |
- Greenhalgh, Trisha, et al.
(författare)
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The NASSS-CAT Tools for Understanding, Guiding, Monitoring, and Researching Technology Implementation Projects in Health and Social Care : Protocol for an Evaluation Study in Real-World Settings
- 2020
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Ingår i: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Projects to implement health care and social care innovations involving technologies are typically ambitious and complex. Many projects fail. Greenhalgh et al’s nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework was developed to analyze the varied outcomes of such projects.Objective: We sought to extend the NASSS framework to produce practical tools for understanding, guiding, monitoring, and researching technology projects in health care or social care settings.Methods: Building on NASSS and a complexity assessment tool (CAT), the NASSS-CAT tools were developed (in various formats) in seven co-design workshops involving 50 stakeholders (industry executives, technical designers, policymakers, managers, clinicians, and patients). Using action research, they were and are being tested prospectively on a sample of case studies selected for variety in conditions, technologies, settings, scope and scale, policy context, and project goals.Results: The co-design process resulted in four tools, available as free downloads. NASSS-CAT SHORT is a taster to introduce the instrument and gauge interest. NASSS-CAT LONG is intended to support reflection, due diligence, and preliminary planning. It maps complexity through stakeholder discussion across six domains, using free-text open questions (designed to generate a rich narrative and surface uncertainties and interdependencies) and a closed-question checklist; this version includes an action planning section. NASSS-CAT PROJECT is a 35-item instrument for monitoring how subjective complexity in a technology implementation project changes over time. NASSS-CAT INTERVIEW is a set of prompts for conducting semistructured research or evaluation interviews. Preliminary data from empirical case studies suggest that the NASSS-CAT tools can potentially identify, but cannot always help reconcile, contradictions and conflicts that block projects’ progress.Conclusions: The NASSS-CAT tools are a useful addition to existing implementation tools and frameworks. Further support of the implementation projects is ongoing. We are currently producing digital versions of the tools, and plan (subject to further funding) to establish an online community of practice for people interested in using and improving the tools, and hold workshops for building cross-project collaborations. International Registered Report Identifier (IRRID): DERR1-10.2196/16861
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| 4. |
- Nordberg, Agneta, et al.
(författare)
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A European multicentre PET study of fibrillar amyloid in Alzheimer's disease
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:1, s. 104-114
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. In this study 238 [C-11]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [C-11]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 +/- 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 +/- 8 years) and 51 healthy controls (mean age 67.4 +/- 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 +/- 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. [C-11]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [C-11]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [C-11]PIB retention was observed in MCI ApoE epsilon 4 carriers compared to non-ApoE epsilon 4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. This study demonstrated the robustness of [C-11]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
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| 5. |
- Vandenberghe, Rik, et al.
(författare)
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Binary classification of F-18-flutemetamol PET using machine learning: Comparison with visual reads and structural MRI
- 2013
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Ingår i: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 64, s. 517-525
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Tidskriftsartikel (refereegranskat)abstract
- F-18-flutemetamol is a positron emission tomography (PET) tracer for in vivo amyloid imaging. The ability to classify amyloid scans in a binary manner as 'normal' versus 'Alzheimer-like', is of high clinical relevance. We evaluated whether a supervised machine learning technique, support vector machines (SVM), can replicate the assignments made by visual readers blind to the clinical diagnosis, which image components have highest diagnostic value according to SVM and how F-18-flutemetamol-based classification using SVM relates to structural MRI-based classification using SVM within the same subjects. By means of SVM with a linear kernel, we analyzed F-18-flutemetamol scans and volumetric MRI scans from 72 cases from the F-18-flutemetamol phase 2 study (27 clinically probable Alzheimer's disease (AD), 20 amnestic mild cognitive impairment (MCI), 25 controls). In a leave-one-out approach, we trained the F-18-flutemetamol based classifier by means of the visual reads and tested whether the classifier was able to reproduce the assignment based on visual reads and which voxels had the highest feature weights. The F-18-flutemetamol based classifier was able to replicate the assignments obtained by visual reads with 100% accuracy. The voxels with highest feature weights were in the striatum, precuneus, cingulate and middle frontal gyrus. Second, to determine concordance between the gray matter volume- and the F-18-flutemetamol-based classification, we trained the classifier with the clinical diagnosis as gold standard. Overall sensitivity of the F-18-flutemetamol- and the gray matter volume-based classifiers were identical (85.2%), albeit with discordant classification in three cases. Specificity of the F-18-flutemetamol based classifier was 92% compared to 68% for MRI. In the MCI group, the F-18-flutemetamol based classifier distinguished more reliably between converters and non-converters than the gray matter-based classifier. The visual read-based binary classification of F-18-flutemetamol scans can be replicated using SVM. In this sample the specificity of F-18-flutemetamol based SVM for distinguishing AD from controls is higher than that of gray matter volume-based SVM. (C) 2012 Elsevier Inc. All rights reserved.
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| 6. |
- Vandenberghe, Rik, et al.
(författare)
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F-18-Flutemetamol Amyloid Imaging in Alzheimer Disease and Mild Cognitive Impairment A Phase 2 Trial
- 2010
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 68:3, s. 319-329
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The most widely studied positron emission tomography ligand for in vivo P-amyloid imaging is C-11-Pittsburgh compound B (C-11-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the F-18-labeled PIB derivative F-18-flutemetamol could significantly enhance access to this novel technology. Methods: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of F-18-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for F-18-flutemetamol and its parent molecule C-11-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of F-18-flutemetamol SUVRs in 5 of the AD subjects. Results: Blinded visual assessments of F-18-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical F-18-flutemetamol SUVRs and C-11-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation: F-18-Flutemetamol performs similarly to the C-11-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use. ANN NEUROL 2010;68:319-329
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