Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort. - Institut de Neurosciences des Systèmes Access content directly
Journal Articles Neurology Year : 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 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
4 CHU Bordeaux
5 BPH - Bordeaux population health
6 ISPED - Institut de Santé Publique, d'Epidémiologie et de Développement
7 CIC Bordeaux
8 Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux]
9 Université Paris-Saclay
10 BAOBAB - Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields
11 CATI - Centre d'Acquisition et de Traitement des Images [Paris] = CATI Multicenter Neuroimaging Platform
12 CHU Pitié-Salpêtrière [AP-HP]
13 SU - Sorbonne Université
14 IM2A - Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre]
15 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
16 LEASP - Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps
17 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 Excellence Laboratory LabEx DISTALZ
20 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
21 FMTS - Fédération de Médecine Translationnelle de Strasbourg
22 Hôpital Lariboisière-Fernand-Widal [APHP]
23 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
24 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
25 EA 4468 - Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies
26 CHU Montpellier
27 INS - Institut de Neurosciences des Systèmes
28 APHM - Assistance Publique - Hôpitaux de Marseille
29 UA - Université d'Angers
30 CHU Angers - Centre Hospitalier Universitaire d'Angers
31 Pôle de Neurosciences - Service de Gériatrie [Angers]
32 HCL - Hospices Civils de Lyon
33 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
34 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
35 CHU Amiens-Picardie
36 CHU Rouen
37 UNIROUEN - Université de Rouen Normandie
38 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
39 CMRR - Centre Mémoire de Ressources et de Recherche [Grenoble]
40 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
41 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
42 CRMSB - Centre de résonance magnétique des systèmes biologiques
43 Service d'Addictologie et Pathologie Duelles [CHU Clermont-Ferrand]
44 UCA - Université Clermont Auvergne
45 IP - Institut Pascal
Karim Bennys
  • Function : Author

Abstract

Background and objective - Blood biomarkers for Alzheimer 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 2,323 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, 2,277 individuals had at least 1 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, < 0.0001) and were associated with amyloid-PET status ( < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 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 clinical dementia rating (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 + apolipoprotein E 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 affect 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.
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hal-03823330 , version 1 (27-05-2024)

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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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