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Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort

dc.rights.licenseopenen_US
hal.structure.identifierCentre Mémoire de Ressources et de Recherches [Bordeaux]
dc.contributor.authorPLANCHE, Vincent
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUTELOUP, Vincent
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorPELLEGRIN, Isabelle
dc.contributor.authorMANGIN, Jean-Francois
dc.contributor.authorDUBOIS, Bruno
dc.contributor.authorOUSSET, Pierre-Jean
dc.contributor.authorPASQUIER, Florence
dc.contributor.authorBLANC, Frédéric
dc.contributor.authorPAQUET, Claire
dc.contributor.authorHANON, Olivier
dc.contributor.authorBENNYS, Karim
dc.contributor.authorCECCALDI, Mathieu
dc.contributor.authorANNWEILER, Cédric
dc.contributor.authorKROLAK-SALMON, Pierre
dc.contributor.authorGODEFROY, Olivier
dc.contributor.authorWALLON, David
dc.contributor.authorSAUVEE, Mathilde
dc.contributor.authorBOUTOLEAU-BRETONNIÈRE, Claire
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBOURDEL-MARCHASSON, Isabelle
dc.contributor.authorJALENQUES, Isabelle
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHENE, Genevieve
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.date.accessioned2023-11-16T08:53:21Z
dc.date.available2023-11-16T08:53:21Z
dc.date.issued2023-01-31
dc.identifier.issn0028-3878en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184802
dc.description.abstractEnBACKGROUND: Blood biomarkers for Alzheimer's disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints. METHODS: The MEMENTO cohort enrolled 2323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aβ42/40 ratio, total-tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period. RESULTS: Overall, 2277 individuals had at least one baseline blood biomarker available (n=357 for CSF subsample, n=649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total-tau were mildly correlated with their equivalence in the CSF (r=0.33 to 0.46, p<0.0001) and were associated with amyloid-PET status (p<0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (AUC=0.74 [95%CI=0.69-0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index=0.73 [95%CI=0.69-0.77]); its accuracy was higher in patients with CDR=0 (c-index=0.83 [95% CI=0.69;0.97]) than in patients with CDR=0.5 (c-index=0.70 [95% CI=0.66;0.74]). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index=0.88 [95%CI=0.86-0.91] and performance increased to 0.90 [95%CI=0.88;0.92] when adding blood p181-tau+Aβ42/40. A "research" reference model (clinical model+ApoE genotype and AD-signature on MRI) had a c-index=0.91 [95%CI=0.89-0.93] increasing to 0.92 [95%CI=0.90;0.93] when adding blood p181-tau+Aβ42/40. Chronic kidney disease and vascular comorbidities did not impact predictive performances. DISCUSSION: In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enValidity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort
dc.title.alternativeNeurologyen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1212/WNL.0000000000201479en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.subject.halSciences de l'ingénieur [physics]en_US
dc.identifier.pubmed36261295en_US
bordeaux.journalNeurologyen_US
bordeaux.pageE473-E484en_US
bordeaux.volume100en_US
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.institutionINSERM
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFondation Plan Alzheimeren_US
bordeaux.identifier.funderIDAvid Radiopharmaceuticalsen_US
bordeaux.identifier.funderIDGE Healthcareen_US
bordeaux.identifier.funderIDFujirebio Europeen_US
bordeaux.import.sourcehal
hal.identifierhal-03823330
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Neurology&amp;rft.date=2023-01-31&amp;rft.volume=100&amp;rft.issue=5&amp;rft.spage=E473-E484&amp;rft.epage=E473-E484&amp;rft.eissn=0028-3878&amp;rft.issn=0028-3878&amp;rft.au=PLANCHE,%20Vincent&amp;BOUTELOUP,%20Vincent&amp;PELLEGRIN,%20Isabelle&amp;MANGIN,%20Jean-Francois&amp;DUBOIS,%20Bruno&amp;rft.genre=article


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