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-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE To determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ 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®, 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 Aβ1-40 and Aβ1-42 levels, as well as cognitive, functional, and behavioral measures were determined. RESULTS CSF Aβ1-42 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 Aβ1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aβ1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal 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 Aβ1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.