Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Gemma Salvadó, José Luis Molinuevo, Anna Brugulat-Serrat, Carles Falcon, Oriol Grau-Rivera, Marc Suárez-Calvet, Javier Pavia, Aida Niñerola-Baizán, Andrés Perissinotti, Francisco Lomeña, Carolina Minguillon, Karine Fauria, Henrik Zetterberg, Kaj Blennow, Juan Domingo Gispert, for the Alzheimer’s Disease Neuroimaging Initiative, for the ALFA Study

ABSTRACT

BACKGROUND: The Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Centiloid thresholds that maximize the agreement against core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in two large independent cohorts. METHODS: A total of 516 participants of the ALFA+ Study (N = 205) and ADNI (N = 311) underwent amyloid PET imaging ([18F]flutemetamol and [18F]florbetapir, respectively) and core AD CSF biomarker determination using Elecsys® tests. Tracer uptake was quantified in Centiloid units (CL). Optimal Centiloid cut-offs were sought that maximize the agreement between PET and dichotomous determinations based on CSF levels of Aβ42, tTau, pTau, and their ratios, using pre-established reference cut-off values. To this end, a receiver operating characteristic analysis (ROC) was conducted, and Centiloid cut-offs were calculated as those that maximized the Youden's J Index or the overall percentage agreement recorded. RESULTS: All Centiloid cut-offs fell within the range of 25-35, except for CSF Aβ42 that rendered an optimal cut-off value of 12 CL. As expected, the agreement of tau/Aβ42 ratios was higher than that of CSF Aβ42. Centiloid cut-off robustness was confirmed even when established in an independent cohort and against variations of CSF cut-offs. CONCLUSIONS: A cut-off of 12 CL matches previously reported values derived against postmortem measures of AD neuropathology. Together with these previous findings, our results flag two relevant inflection points that would serve as boundary of different stages of amyloid pathology: one around 12 CL that marks the transition from the absence of pathology to subtle pathology and another one around 30 CL indicating the presence of established pathology. The derivation of robust and generalizable cut-offs for core AD biomarkers requires cohorts with adequate representation of intermediate levels. TRIAL REGISTRATION: ALFA+ Study, NCT02485730 ALFA PET Sub-study, NCT02685969. More... »

PAGES

27

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13195-019-0478-z

DOI

http://dx.doi.org/10.1186/s13195-019-0478-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112945278

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30902090


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