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

Vincent Planche 1, 2 Vincent Bouteloup 3 Isabelle Pellegrin 4, 5 Jean-Francois Mangin 6 Bruno Dubois 7 Pierre-Jean Ousset 8 Florence Pasquier 9 Frédéric Blanc 10, 11 Claire Paquet 12, 13 Olivier Hanon 14 Karim Bennys 15 Mathieu Ceccaldi 16 Cédric Annweiler 17, 18, 19, 20 Pierre Krolak-Salmon 21, 22, 23 Olivier Godefroy 24, 25 David Wallon 26, 27 Mathilde Sauvee 28 Claire Boutoleau-Bretonnière 29 Isabelle Bourdel-Marchasson 30 Isabelle Jalenques 31, 32 Genevieve Chene 3, 33, 34 Carole Dufouil 3 
11 LAAS-I2C - Service Instrumentation Conception Caractérisation
LAAS - Laboratoire d'analyse et d'architecture des systèmes
Abstract : 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.
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Soumis le : jeudi 20 octobre 2022 - 18:41:28
Dernière modification le : lundi 28 novembre 2022 - 14:46:45



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, 2022, pp.10.1212/WNL.0000000000201479. ⟨10.1212/WNL.0000000000201479⟩. ⟨hal-03823330⟩



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