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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 13/2022

Open Access 22-07-2022 | Magnetic Resonance Imaging | Original Article

Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer’s disease: additional results from the AMBAR study

Authors: Gemma Cuberas-Borrós, Isabel Roca, Joan Castell-Conesa, Laura Núñez, Mercè Boada, Oscar L. López, Carlota Grifols, Miquel Barceló, Deborah Pareto, Antonio Páez

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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Abstract

Purpose

This study was designed to detect structural and functional brain changes in Alzheimer’s disease (AD) patients treated with therapeutic plasma exchange (PE) with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial.

Methods

Mild-to-moderate AD patients were randomized into four arms: three arms receiving PE with albumin (one with low-dose albumin, and two with low/high doses of albumin alternated with IVIG), and a placebo (sham PE) arm. All arms underwent 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Magnetic resonance imaging (MRI) volumetric analyses and regional and statistical parametric mapping (SPM) analysis on 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) were performed.

Results

MRI analyses (n = 198 patients) of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group (p < 0.05 in 3 structures vs. 4 to 9 in other groups). The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. SPM 18FDG-PET analyses (n = 213 patients) showed a worsening of metabolic activity in the specific areas affected in AD (posterior cingulate, precuneus, and parieto-temporal regions). The high-albumin + IVIG treatment group showed the greatest metabolic stability over the course of the study, i.e., the smallest percent decline in metabolism (MaskAD), and least progression of defect compared to placebo.

Conclusions

PE with albumin replacement was associated with fewer deleterious changes in subcortical structures and less metabolic decline compared to the typical of the progression of AD. This effect was more marked in the group treated with high albumin + IVIG.

Trial registration

(AMBAR trial registration: EudraCT#: 2011–001,598-25; ClinicalTrials.gov ID: NCT01561053).
Appendix
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Metadata
Title
Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer’s disease: additional results from the AMBAR study
Authors
Gemma Cuberas-Borrós
Isabel Roca
Joan Castell-Conesa
Laura Núñez
Mercè Boada
Oscar L. López
Carlota Grifols
Miquel Barceló
Deborah Pareto
Antonio Páez
Publication date
22-07-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05915-5

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