%0 Journal Article %J J Alzheimers Dis %D 2018 %T Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers. %A Marizzoni, Moira %A Ferrari, Clarissa %A Jovicich, Jorge %A Albani, Diego %A Babiloni, Claudio %A Cavaliere, Libera %A Didic, Mira %A Forloni, Gianluigi %A Galluzzi, Samantha %A Hoffmann, Karl-Titus %A Molinuevo, José Luis %A Nobili, Flavio %A Parnetti, Lucilla %A Payoux, Pierre %A Ribaldi, Federica %A Rossini, Paolo Maria %A Schönknecht, Peter %A Soricelli, Andrea %A Hensch, Tilman %A Tsolaki, Magda %A Visser, Pieter Jelle %A Wiltfang, Jens %A Richardson, Jill C %A Bordet, Régis %A Blin, Olivier %A Frisoni, Giovanni B %X

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.

%B J Alzheimers Dis %8 2018 Jun 09 %G eng %R 10.3233/JAD-180152