Plasma Exchange May Slow Alzheimer’s Disease Cognitive and Functional Decline: Phase 2b/3 Clinical Study Findings

Patients with mild to moderate Alzheimer’s disease treated with therapeutic plasma exchange (TPE) outperformed placebo group patients on co-primary cognitive and activity-of-daily-living endpoints, according to complete findings from the Grifols- sponsored AMBAR study. The working hypothesis for this experimental intervention is that repeated removal of albumin bound to the suspected pathogenic agent (amyloid beta), replaced by fresh albumin, can facilitate removal of amyloid beta from the cerebrospinal fluid and the brain itself.

Initiated in 2012, this Phase 2b/3 study randomized 347 patients on a 1:1:1:1 basis to a control (placebo) sham procedure arm and three active treatment arms, all of which received a series of six TPE treatments with 5 percent albumin replacement, followed by 1) monthly low-volume plasma exchange (LVPE) with infusion of 20 grams of albumin, 2) LVPE with infusion of 20 grams of albumin alternated with infusions of 10 grams of intravenous immune globulin (IVIG) or 3) LVPE with infusion of 40 grams of albumin alternated with 20 grams of IVIG.

At 14 months from baseline compared to the placebo group, TPE-treated patients experienced 52 percent lesser decline in the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score (P = 0.03) with a strong trend for lesser deterioration in the Alzheimer’s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog) (P = 0.06). TPE-treated patients also scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (71 percent less decline; P = 0.002) and ADCS-CGIC scales (100 percent less decline; P < 0.0001). The subset of TPE- treated patients with moderate disease had 61 percent better scores on ADCS-ADL and ADAS-Cog, while the subset with mild disease did not significantly improve.

“This trial suggests that plasma exchange with albumin replacement could slow cognitive and functional decline in Alzheimer’s disease, although further studies are warranted,” the investigators concluded.