Efficacy and Safety of Plasma Exchange with 5% Albumin to Modify Cerebrospinal Fluid and Plasma Amyloid-β Concentrations and Cognition Outcomes in Alzheimer's Disease Patients: A Multicenter, Randomized, Controlled Clinical Trial.

Background: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-beta (A beta) peptide between cerebrospinal fluid (CSF) and plasma compartments. Objective: To determine whether plasma exchange (PE) with albumin replacement was able to modify A beta concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). Methods: In a multicenter, randomized, patient-and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein (R), Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi-weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF A beta(1-40) and A beta(1-42) levels, as well as cognitive, functional, and behavioral measures were determined. Results: CSF A beta(1-42) levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma A beta(1-42) levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma A beta(1-40) levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and SemanticVerbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). Conclusion: PE with human albumin modified CSF and plasma A beta(1-42) levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.