Neuroimaging, randomized,, controlled, replacement, mild-to-moderate, Alzheimer, additional
Plasma exchange (PE) with albumin replacement is currently being investigated by several organisations as a new therapeutic approach for Alzheimer's disease (AD).
Routine PE removal of an AD patient's plasma would favor elimination of albumin‐bound β amyloid , and possibly, other pathogenic elements. In addition, replacement with fresh therapeutic albumin can restore the antioxidant capacity of AD patient plasma, as albumin is highly oxidized and glycated. Furthermore, a therapeutic action at the vascular level can have a positive impact on dementia.
This new study by Gemma Cuberas-Borrós and colleagues from Spain, was designed to detect structural and functional brain changes in Alzheimer's disease patients treated with therapeutic plasma exchange with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial. The AMBAR trial enrolled patients at 41 sites: 19 in Spain and 22 in the USA.
Mild-to-moderate Alzheimer's disease patients were randomized into four arms: three arms receiving plasma exchange with albumin, and a placebo arm.
There were two phases for treatment administration:
- During intensive treatment phase, the three treatment groups received weekly conventional therapeutic PE (TPE) with albumin (Albutein® 5%, Grifols) replacement, through peripheral or central venous access, for 6 weeks.
- This was followed by a 12-month maintenance period with monthly low-volume PE (LVPE) during which three different treatment modalities were administered.
During the 12-month maintenance period: - one group received LVPE with low-dose (20 g; 100 mL) 20% albumin (Albutein® 20%, Grifols); - one group received low-dose albumin alternated with low-dose (10 g; 200 mL) IVIG (Flebogamma® 5% DIF, Grifols) every 4 months; - one group received high-dose (40 g; 200 mL) 20% albumin alternated with high-dose (20 g; 400 mL) IVIG every 4 months.
The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. MRI analyses of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group. I.e., the smallest percent decline in metabolism, and least progression of defect compared to placebo.
Particularly in moderate AD patients, there was a significant difference in the extension of defect pattern between high albumin + IVIG and the rest of treatment arms.