Cargando…

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

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 A...

Descripción completa

Detalles Bibliográficos
Autores principales: Svaldi, Diana Otero, Higgins, Ixavier A., Holdridge, Karen C., Yaari, Roy, Case, Michael, Bracoud, Luc, Scott, David, Shcherbinin, Sergey, Sims, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237342/
https://www.ncbi.nlm.nih.gov/pubmed/35783453
http://dx.doi.org/10.1002/trc2.12313
_version_ 1784736762436780032
author Svaldi, Diana Otero
Higgins, Ixavier A.
Holdridge, Karen C.
Yaari, Roy
Case, Michael
Bracoud, Luc
Scott, David
Shcherbinin, Sergey
Sims, John R.
author_facet Svaldi, Diana Otero
Higgins, Ixavier A.
Holdridge, Karen C.
Yaari, Roy
Case, Michael
Bracoud, Luc
Scott, David
Shcherbinin, Sergey
Sims, John R.
author_sort Svaldi, Diana Otero
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9237342
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-92373422022-06-30 Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia Svaldi, Diana Otero Higgins, Ixavier A. Holdridge, Karen C. Yaari, Roy Case, Michael Bracoud, Luc Scott, David Shcherbinin, Sergey Sims, John R. Alzheimers Dement (N Y) Short Report 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. John Wiley and Sons Inc. 2022-06-27 /pmc/articles/PMC9237342/ /pubmed/35783453 http://dx.doi.org/10.1002/trc2.12313 Text en © 2022 Eli Lilly and Company. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Short Report
Svaldi, Diana Otero
Higgins, Ixavier A.
Holdridge, Karen C.
Yaari, Roy
Case, Michael
Bracoud, Luc
Scott, David
Shcherbinin, Sergey
Sims, John R.
Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title_full Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title_fullStr Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title_full_unstemmed Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title_short Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia
title_sort magnetic resonance imaging measures of brain volumes across the expedition trials in mild and moderate alzheimer's disease dementia
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237342/
https://www.ncbi.nlm.nih.gov/pubmed/35783453
http://dx.doi.org/10.1002/trc2.12313
work_keys_str_mv AT svaldidianaotero magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT higginsixaviera magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT holdridgekarenc magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT yaariroy magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT casemichael magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT bracoudluc magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT scottdavid magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT shcherbininsergey magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia
AT simsjohnr magneticresonanceimagingmeasuresofbrainvolumesacrosstheexpeditiontrialsinmildandmoderatealzheimersdiseasedementia