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Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2019; Vol. 69 (1), pp. 3-14. - Publication Year :
- 2019
-
Abstract
- 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.<br />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.<br />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.<br />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).<br />Conclusion: MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.
- Subjects :
- Aged
Alzheimer Disease cerebrospinal fluid
Amnesia cerebrospinal fluid
Amyloid beta-Peptides cerebrospinal fluid
Biomarkers cerebrospinal fluid
Cognitive Dysfunction cerebrospinal fluid
Disease Progression
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Prodromal Symptoms
tau Proteins cerebrospinal fluid
Alzheimer Disease diagnostic imaging
Amnesia diagnostic imaging
Brain diagnostic imaging
Cognitive Dysfunction diagnostic imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 69
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 29914031
- Full Text :
- https://doi.org/10.3233/JAD-180152