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- Boccardi, M., et al.
(författare)
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The strategic biomarker roadmap for the validation of Alzheimer's diagnostic biomarkers: methodological update
- 2021
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48, s. 2070-2085
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Tidskriftsartikel (refereegranskat)abstract
- Background The 2017 Alzheimer's disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1-2), clinical validity (Phases 3-4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps and research priorities, accelerating the route towards clinical implementation. Within an initiative aimed to assess the development of biomarkers of tau pathology, we revised this methodology consistently with progress in AD research. Methods We critically appraised the adequacy of the 2017 Biomarker Roadmap within current diagnostic frameworks, discussed updates at a workshop convening the Alzheimer's Association and 8 leading AD biomarker research groups, and detailed the methods to allow consistent assessment of aims achievement for tau and other AD diagnostic biomarkers. Results The 2020 update applies to all AD diagnostic biomarkers. In Phases 2-3, we admitted a greater variety of study designs (e.g., cross-sectional in addition to longitudinal) and reference standards (e.g., biomarker confirmation in addition to clinical progression) based on construct (in addition to criterion) validity. We structured a systematic data extraction to enable transparent and formal evidence assessment procedures. Finally, we have clarified issues that need to be addressed to generate data eligible to evidence-to-decision procedures. Discussion This revision allows for more versatile and precise assessment of existing evidence, keeps up with theoretical developments, and helps clinical researchers in producing evidence suitable for evidence-to-decision procedures. Compliance with this methodology is essential to implement AD biomarkers efficiently in clinical research and diagnostics.
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- Bucci, M, et al.
(författare)
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Alzheimer's disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:10, s. 5888-5898
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Tidskriftsartikel (refereegranskat)abstract
- For early detection of Alzheimer’s disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status for Aβ42 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category and to assess their ability to predict longitudinal cognitive decline. A subset of 282 patients, who had had at the same time PET investigations with amyloid-β and tau tracers, CSF sampling, and structural MRI (18% within 13 months), was selected from the ADNI dataset. The participants were grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-β-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-β PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume (MRI)(N)) positivity in ATN was assessed with Cohen’s Kappa. Linear mixed-effects models were used to predict decline in the episodic memory. There was moderate agreement between PET and CSF for A biomarkers (Kappa = 0.39–0.71), while only fair agreement for T biomarkers (Kappa ≤ 0.40, except AD) and discordance for N biomarkers across all groups (Kappa ≤ 0.14) was found. Baseline PET tau predicted longitudinal decline in episodic memory irrespective of CSF p-Tau181 positivity (p ≤ 0.02). Baseline PET tau and amyloid-β predicted decline in episodic memory (p ≤ 0.0001), but isolated PET amyloid-β did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-β were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not interchangeable. PET tau positivity was superior to CSF p-Tau181 and PET amyloid-β in predicting cognitive decline in the AD continuum within 3 years of follow-up.
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