Published 2019
| Version v1
Publication
Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers
Creators
- Marizzoni, Moira
- Ferrari, Clarissa
- Jovicich, Jorge
- Albani, Diego
- Babiloni, Claudio
- Cavaliere, Libera
- Didic, Mira
- FORLONI, GIANLUIGI
- Galluzzi, Samantha
- Hoffmann, Karl-Titus
- Molinuevo, José Luis
- Nobili, Flavio
- Parnetti, Lucilla
- Payoux, Pierre
- Ribaldi, Federica
- Rossini, Paolo Maria
- Schönknecht, Peter
- Soricelli, Andrea
- Hensch, Tilman
- Tsolaki, Magda
- Visser, Pieter Jelle
- Wiltfang, Jens
- Richardson, Jill C
- Bordet, Régis
- Blin, Olivier
- Frisoni, Giovanni B
Contributors
Others:
- Marizzoni, Moira
- Ferrari, Clarissa
- Jovicich, Jorge
- Albani, Diego
- Babiloni, Claudio
- Cavaliere, Libera
- Didic, Mira
- Forloni, Gianluigi
- Galluzzi, Samantha
- Hoffmann, Karl-Titu
- Molinuevo, José Lui
- Nobili, Flavio
- Parnetti, Lucilla
- Payoux, Pierre
- Ribaldi, Federica
- Rossini, Paolo Maria
- Schönknecht, Peter
- Soricelli, Andrea
- Hensch, Tilman
- Tsolaki, Magda
- Visser, Pieter Jelle
- Wiltfang, Jen
- Richardson, Jill C
- Bordet, Régi
- Blin, Olivier
- Frisoni, Giovanni B
Description
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).
CONCLUSION:
MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/923101
- URN
- urn:oai:iris.unige.it:11567/923101
Origin repository
- Origin repository
- UNIGE