Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort. - Université de Picardie Jules Verne Accéder directement au contenu
Article Dans Une Revue Neurology Année : 2023

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

1 UB - Université de Bordeaux
2 Centre Mémoire de Ressources et de Recherches [Bordeaux]
3 BPH - Bordeaux population health
4 ImmunoConcept - Immunology from Concept and Experiments to Translation
5 Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux]
6 Université Paris-Saclay
7 ICM - Institut du Cerveau = Paris Brain Institute
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 CSHMyelo - U1287 Inserm - Cellules souches hématopoïétiques et développement des hémopathies myéloïdes
10 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
11 Hôpital Lariboisière-Fernand-Widal [APHP]
12 OPTeN (UMR_S_1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
13 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
14 Département de neurologie [Montpellier]
15 INS - Institut de Neurosciences des Systèmes
16 UA - Université d'Angers
17 CHU Angers - Centre Hospitalier Universitaire d'Angers
18 LPPL - Laboratoire de Psychologie des Pays de la Loire
19 CONFLUENCES - SFR UA 4201 Confluences
20 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
21 HCL - Hospices Civils de Lyon
22 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
23 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
24 CHU Amiens-Picardie
25 CHU Rouen
26 UNIROUEN - Université de Rouen Normandie
27 CMRR - Centre Mémoire de Ressources et de Recherche [Grenoble]
28 CHU Nantes - Centre hospitalier universitaire de Nantes
29 CRMSB - Centre de résonance magnétique des systèmes biologiques
30 Service d'Addictologie et Pathologie Duelles [CHU Clermont-Ferrand]
31 NPsy-Sydo - Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux
32 CHU Bordeaux
33 CIC Bordeaux

Résumé

BACKGROUND: 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.

Dates et versions

hal-03823330 , version 1 (20-10-2022)

Identifiants

Citer

Vincent Planche, Vincent Bouteloup, Isabelle Pellegrin, Jean-Francois Mangin, Bruno Dubois, et al.. Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort.. Neurology, 2023, 100 (5), pp.E473-E484. ⟨10.1212/WNL.0000000000201479⟩. ⟨hal-03823330⟩
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