| 1. |
- Festari, Cristina, et al.
(author)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Journal article (peer-reviewed)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 2. |
- Bischof, Gérard N., et al.
(author)
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Clinical validity of second-generation tau PET tracers as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework
- 2021
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2110-2120
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Research review (peer-reviewed)abstract
- Purpose: In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context. Methods: All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1–2), clinical validity (phase 3–4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all. Results: The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway. Conclusion: The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.
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| 3. |
- Chiotis, Konstantinos, et al.
(author)
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Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework
- 2021
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2086-2096
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Research review (peer-reviewed)abstract
- Purpose: The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. Results: PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand’s diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. Conclusion: Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.
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| 4. |
- Frisoni, Giovanni B., et al.
(author)
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European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
- 2024
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In: The Lancet Neurology. - 1474-4422. ; 23:3, s. 302-312
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Research review (peer-reviewed)abstract
- The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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| 5. |
- Mendes, Augusto J., et al.
(author)
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Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort
- 2024
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In: JOURNAL OF NEUROLOGY. - 0340-5354 .- 1432-1459.
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Journal article (peer-reviewed)abstract
- Background and objective Phosphorylated tau (p-tau) 217 has recently received attention because it seems more reliable than other p-tau variants for identifying Alzheimer's disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma and CSF p-tau217 with p-tau181 and p-tau231 in a memory clinic cohort.Methods The study included 114 participants (CU = 33; MCI = 67; Dementia = 14). The p-tau variants were correlated versus continuous measures of amyloid (A) and tau (T)-PET. The p-tau phospho-epitopes were assessed through: (i) effect sizes (delta) between diagnostic and A +/- and T +/- groups; (ii) receiver operating characteristic (ROC) analyses in A-PET and T-PET.Results The correlations between both plasma and CSF p-tau217 with A-PET and T-PET (r range 0.64-0.83) were stronger than those of p-tau181 (r range 0.44-0.79) and p-tau231 (r range 0.46-0.76). Plasma p-tau217 showed significantly higher diagnostic accuracy than p-tau181 and p-tau231 in (i) differences between diagnostic and biomarker groups (delta(range): p-tau217 = 0.55-0.96; p-tau181 = 0.51-0.67; p-tau231 = 0.53-0.71); (ii) ROC curves to identify A-PET and T-PET positivity (AUC(average): p-tau217 = 0.96; p-tau181 = 0.76; p-tau231 = 0.79). On the other hand, CSF p-tau217 (AUC(average) = 0.95) did not reveal significant differences in A-PET and T-PET AUC than p-tau181 (AUC(average) = 0.88) and p-tau231 (AUC(average) = 0.89).Discussion Plasma p-tau217 demonstrated better performance in the identification of AD pathology and clinical phenotypes in comparison with other variants of p-tau in a memory clinic cohort. Furthermore, p-tau217 had comparable performance in plasma and CSF. Our findings suggest the potential of plasma p-tau217 in the diagnosis and screening for AD, which could allow for a decreased use of invasive biomarkers in the future.
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