Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia.

Autor: Svaldi DO; Eli Lilly and Company Indianapolis Indiana USA., Higgins IA; Eli Lilly and Company Indianapolis Indiana USA., Holdridge KC; Eli Lilly and Company Indianapolis Indiana USA., Yaari R; Eli Lilly and Company Indianapolis Indiana USA., Case M; Eli Lilly and Company Indianapolis Indiana USA., Bracoud L; Clario Lyon France., Scott D; Clario San Mateo California USA., Shcherbinin S; Eli Lilly and Company Indianapolis Indiana USA., Sims JR; Eli Lilly and Company Indianapolis Indiana USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (New York, N. Y.) [Alzheimers Dement (N Y)] 2022 Jun 27; Vol. 8 (1), pp. e12313. Date of Electronic Publication: 2022 Jun 27 (Print Publication: 2022).
DOI: 10.1002/trc2.12313
Abstrakt: Introduction: Solanezumab is a monoclonal antibody that preferentially binds soluble amyloid beta and promotes its clearance from the brain. The aim of this post hoc analysis was to assess the effect of low-dose solanezumab (400 mg) on global brain volume measures in patients with mild or moderate Alzheimer's disease (AD) dementia quantified using volumetric magnetic resonance imaging (vMRI) data from the EXPEDITION clinical trial program.
Methods: Patients with mild or moderate AD (EXPEDITION and EXPEDITION2) and mild AD (EXPEDITION3), were treated with either placebo or solanezumab (400 mg) every 4 weeks (Q4W) for 76 weeks. vMRI scans were acquired at baseline and at 80 weeks from 427 MRI facilities using a standardized imaging protocol. Whole brain volume (WBV) and ventricle volume (VV) changes were estimated at 80 weeks using either boundary shift integral (EXPEDITION and EXPEDITION2) or tensor-based morphometry (EXPEDITION3).
Results: The pooled cohort used for this study consisted of participants with vMRI at baseline and week 80 across the three trials. Analyzed patient subgroups comprised full patient cohort ( N = 2933), apolipoprotein E ( APOE ) ε4 + carriers ( N = 1835), and patients with mild ( N = 2497) or moderate AD dementia ( N = 428). No significant effect (all P -values ≥.05) of treatment was observed in the pooled sample, individual trials, or subgroups of patients with mild or moderate AD or APOE ε4 carriers, in either WBV or VV change.
Discussion: Analysis of patients with mild or moderate AD dementia from baseline to 80 weeks using vMRI measures of WBV and VV changes suggested that low-dose solanezumab was not linked to changes in volumes at 80 weeks. Analysis of the pooled cohort did not demonstrate an effect on brain volumes with treatment. Evaluation of a higher dose of solanezumab in the preclinical stage of AD is currently being undertaken.
Competing Interests: Diana O. Svaldi, Ixavier A. Higgins, Karen C. Holdridge, Roy Yaari, Michael Case, Sergey Shcherbinin, and John R. Sims are all employees and minor shareholders of Eli Lilly and Company. Diana O. Svaldi has received support from Eli Lilly and Company for attending meetings and/or travel. Luc Bracoud and David Scott have nothing to report.
(© 2022 Eli Lilly and Company. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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