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Clinical Trial
. 2022 Jul;18(7):1314-1324.
doi: 10.1002/alz.12477. Epub 2021 Nov 2.

Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study

Mercè Boada  1   2 , Oscar L López  3 , Javier Olazarán  4   5 , Laura Núñez  6 , Michael Pfeffer  7 , Orlando Puente  8 , Gerard Piñol-Ripoll  9 , José E Gámez  10 , Fernando Anaya  11 , Dobri Kiprov  12 , Montserrat Alegret  1 , Carlota Grifols  6 , Miquel Barceló  6 , Jordi Bozzo  6 , Zbigniew M Szczepiorkowski  13   14 , Antonio Páez  6 ; AMBAR Trial Group
Affiliations
Clinical Trial

Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study

Mercè Boada et al. Alzheimers Dement. 2022 Jul.

Abstract

Introduction: We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study).

Methods: Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14.

Results: The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008).

Discussion: PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

Keywords: Alzheimer's disease; albumin; albutein; clinical trial; plasma exchange; plasmapheresis.

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Conflict of interest statement

Merce Boada has been a consultant for Araclon, Avid, Bayer, Elan, Grifols, Janssen/Pfizer, Lilly, Neuroptix, Nutricia, Roche, Sanofi, Biogen, and Servier; and received fees for lectures and funds for research from Araclon, Esteve, Grifols, Janssen, Novartis, Nutricia, Piramal, Pfizer‐Wyett, Roche and Servier. Oscar L. Lopez has been a consultant for Grifols and Lundbeck. Javier Olazaran has been a consultant for Schwabe and Grifols; and received fees for lectures and funds for research from Nutricia. Zbigniew M. Szczepiorkowski has been a consultant for Grifols and Fresenius‐Kabi and participated in research supported by funds from Grifols and Fresenius‐Kabi. Merce Boada, Gerard Pinol‐Rlegret, Jose E. Gamez, Fernando Anaya, PO, Dobri Kiprov, and SH received funding from Grifols to perform this study. Laura Nunez, Montserrat B. Alegret, Carlota Grifols, Jordi Bozzo, and Antonio Paez are full‐time employees of Grifols.

Figures

FIGURE 1
FIGURE 1
Rey Auditory Verbal Learning Test 1 (RAVLT 1; immediate recall) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the treated patient groups (low/high albumin dose, with/without intravenous immunoglobulin [IVIG; n = 78–86] pooled [panels A‐C] or separately [panels D‐F]) and the placebo group (n = 80) at months 2, 6, 9, 12, and 14, is shown
FIGURE 2
FIGURE 2
Rey Auditory Verbal Learning Test 3 (RAVLT 3; short delay recall) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the treated patient groups (low/high albumin dose, with/without intravenous immunoglobulin [IVIG; n = 78–86] pooled [panels A‐C] or separately [panels D‐F]) and the placebo group (n = 80) at months 2, 6, 9, 12, and 14, is shown
FIGURE 3
FIGURE 3
Phonetic Verbal Fluency test (PVF) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the treated patient groups (low/high albumin dose, with/without intravenous immunoglobulin [IVIG; n = 78‐86] pooled [panels A‐C] or separately [panels D‐F]) and the placebo group (n = 80) at months 2, 6, 9, 12, and 14, is shown
FIGURE 4
FIGURE 4
Semantic Verbal Fluency test (SVF) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the treated patient groups (low/high albumin dose, with/without intravenous immunoglobulin [IVIG; n = 7886] pooled [panels A‐C] or separately [panels D‐F]) and the placebo group (n = 80) at months 2, 6, 9, 12, and 14, is shown
FIGURE 5
FIGURE 5
Symbol Digit Modalities Test (SDMT) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the treated patient groups (low/high albumin dose, with/without intravenous immunoglobulin [IVIG; n = 78–86] pooled [panels A‐C] or separately [panels D‐F]) and the placebo group (n = 80) at months 2, 6, 9, 12, and 14, is shown
FIGURE 6
FIGURE 6
Quality of Life‐Alzheimer's Disease test (QoL‐AD: patient rating [panels A‐C] and caregiver rating [panels D‐F]) scores in Alzheimer's disease (AD) patients (all‐patient [panels A, D], moderate AD [panels B, E], and mild AD [panels C, F] populations) treated with plasma exchange (PE) with albumin replacement. TPE denotes the 2‐month period of conventional therapeutic PE; LVPE denotes the 12‐month period of low‐volume PE. Statistical significance (P < .05) and borderline significance (P < .1) between the pooled PE‐treated patient groups (n = 242) and the placebo group (n = 80) at months 6, 9, 12, and 14, is shown
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