Titre :

Predicting and tracking short term disease progression in amnestic mild cognitive impairment patients with prodromal alzheimer''s disease: structural brain biomarkers

Auteur(s) :

Marizzoni, Moira [Auteur]
Ferrari, Clarissa [Auteur]
Jovicich, Jorge [Auteur]
Albani, Diego [Auteur]
Babiloni, Claudio [Auteur]
Cavaliere, Libera [Auteur]
Didic, Mira [Auteur]
Forloni, Gianluigi [Auteur]
Galluzzi, Samantha [Auteur]
Hoffmann, Karl-Titus [Auteur]
Molinuevo, Jose Luis [Auteur]
Nobili, Flavio Mariano [Auteur]
Parnetti, Lucilla [Auteur]
Payoux, Pierre [Auteur]
Ribaldi, Federica [Auteur]
Rossini, Paolo Maria [Auteur]
Schonknecht, Peter [Auteur]
Soricelli, Andrea [Auteur]
Hensch, Tilman [Auteur]
Tsolaki, Magda [Auteur]
Visser, Pieter Jelle [Auteur]
Wiltfang, Jens [Auteur]
Richardson, Jill C. [Auteur]
Bordet, Regis [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Blin, Olivier [Auteur]
Frisoni, Giovanni B. [Auteur]

Titre de la revue :

Journal of Alzheimer's disease . JAD

Nom court de la revue :

J. Alzheimers Dis.

Date de publication :

2018-06-09

ISSN :

1875-8908

Mot(s)-clé(s) en anglais :

mild cognitive impairment
precision medicine
Alzheimer''s disease
biomarkers
clinical trial
magnetic resonance imaging

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

BACKGROUND: Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients. OBJECTIVE: To model ...
Lire la suite >BACKGROUND: Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients. OBJECTIVE: To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression. METHODS: APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort. Linear mixed models were performed 1) with baseline structural biomarker, time, and biomarker×time interaction as factors to predict longitudinal changes in ADAS-cog13, 2) with Aβ42/P-tau status, time, and Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in MRI measures, and 3) to compute sample size estimation for a trial implemented with the selected biomarkers. RESULTS: Only baseline lateral ventricle volume was able to identify a subgroup of prodromal AD patients who declined faster (interaction, p = 0.003). Lateral ventricle volume and medial temporal lobe measures were the biomarkers most sensitive to disease progression (interaction, p≤0.042). Enrichment through ventricular volume reduced the sample size that a clinical trial would require from 13 to 76%, depending on structural outcome variable. The biomarker needing the lowest sample size was the hippocampal subfield GC-ML-DG (granule cells of molecular layer of the dentate gyrus) (n = 82 per arm to demonstrate a 20% atrophy reduction). CONCLUSIONS: MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Troubles cognitifs dégénératifs et vasculaires

Date de dépôt :

2019-11-27T14:31:01Z