Plasma Exchange Elicits Improvements in Patients With Alzheimer Disease

Mercè Boada, MD, PhD

Data from the phase 2b/3 Alzheimer’s Management by Albumin Replacement Trial (AMBAR; NCT01561053) show that patients with Alzheimer disease (AD) treated with plasma exchange (PE) with albumin (Albutein; Grifols) replacement had improvements in memory, language abilities, processing speed, and Quality of Life-Alzheimer’s Disease (QoL-AD) scores. Treated patients also demonstrated stable psychoaffective status.

A total of 347 patients with mild –to moderate AD were randomly assigned 1:1:1:1, to the placebo group (n = 80) or 1 of 3 PE-treatment arms, consisting of different doses of albumin and intravenous immunoglobulin (IVIG): low-albumin (n = 78), low-albumin and IVIG (n = 86), and high-albumin and IVIG (n = 78). Ultimately, 322 patients received treatment. Investigators, led by Mercè Boada, MD, PhD, founder and medical director, Ace Alzheimer Center Barcelona, administered tests at baseline, month 2 (with weekly conventional PE), months 6, 9, and 12 (with monthly low-volume PE), and month 14. 

Compared with the placebo group, the pooled group of PE-treated patients improved in language fluency, measured by the Phonetic Verbal Fluency test, with a large and significant effect seen at month 14 (difference, 2.8 points; 95% CI, 0.66-4.94; P = .007; effect size: >100%, improvement). More significant results were observed in patients with mild AD compared with those with moderate AD. Positive difference from placebo in mean change from baseline for those treated with high-albumin and IVIG reached 6.2 points at month 12 (95% CI, 1.93-10.47; P = .002) and 4.7 points at month 14 (95% CI, –0.21 to 9.61; P = .03; effect size: >100%, improvement). 

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Mental processing speed, measured by the Symbol Digit Modalities Test, increased in the pooled PE-treated group at 14 months and decreased in the placebo group (difference, 2.4 points; 95% CI, –0.36 to 5.16; P = .05; effect size: >100%, improvement). The high-albumin and IVIG group was also statistically different from placebo at 14 months (difference, 3.5 points; 95% CI, –0.63 to 7.63; P = .03; effect size: >100%, improvement).

When evaluating quality of life, PE-treated patients had a significantly better mean change in patient-rated QoL-AD scores compared with placebo (difference, 1.4; 95% CI, 0.09-2.71; P = .02; effect size: >100%, improvement). Patients with mild AD also had a significant improvement compared with placebo (difference, 2.0; 95% CI, 0.32-3.68; P = .01). 

“PE with albumin replacement was able to slow down the decline in neuropsychological capacities associated with AD progression. Importantly, in some cases a trend toward improvement was observed,” Boada et al wrote. “The moderate AD patient cohort showed an improvement in verbal memory while the mild AD patient cohort was characterized by a better response in language fluency and processing speed. The high-albumin+IVIG treatment arm was more frequently associated with stabilization and improvement across outcomes. These effects were accompanied by a positive impact on patient’s QoL and were not associated with a worsening of their neuropsychiatric and psychoaffective status.”

Similar to limitations reported with the primary end points from the AMBAR trial, investigators noted that enrollment was determined based on presence of the AD clinical syndrome rather than absence or presence of a biomarker. Also noted was the blinding procedure, which could be imperfect, as well as the fact that the study did not determine a mechanism of action associated with PE, aside from the assumed Aß-albumin binding.

Previously reported results from the AMBAR study demonstrated a delay in cognitive and functional decline in those with mild to moderate AD. PE-treated patients performed significantly better than those receiving placebo in terms of the co-primary end points: change from baseline of Alzheimer’s Disease Cooperative Study-Activities of Daily Living (52% less decline; P = .03), and a trend for Alzheimer’s Disease Assessment Scale-Cognitive Subscale (66% less decline; P = .06) scores at month 14. The differences in the 3 treatment arms separately compared with placebo (low-albumin, low-albumin+IVG and high-albumin+IVIG) were not statistically significant.

REFERENCE

Boada M, López OL, Olazarán J, et al. Neuropsychosocial, neuropsychiatric, and quality-of-life assessments in Alzheimer’s disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study. Alzheimers Dement. Published online November 2, 2021. doi:10.1002/alz.12477