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.
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.
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DOI：
10.3233/jad-160565
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Páez A
中科院分区：
文献类型：
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作者：
Boada M;Anaya F;Ortiz P;Olazarán J;Shua-Haim JR;Obisesan TO;Hernández I;Muñoz J;Buendia M;Alegret M;Lafuente A;Tárraga L;Núñez L;Torres M;Grifols JR;Ferrer I;Lopez OL;Páez A
背景：在动物模型和人类中进行的研究表明，脑脊液（CSF）和血浆室之间存在淀粉样蛋白-β (a β)肽的动态平衡。目的：探讨血浆置换（PE）与白蛋白替代是否能够改变轻中度阿尔茨海默病（AD）患者脑脊液和血浆中Aβ浓度，并改善认知能力。方法：在一项多中心、随机、患者和非盲、对照、平行组的II期研究中，42例AD患者被按1:1的比例分配到PE治疗组或对照组（假手术）。接受治疗的患者最多接受18次5%白蛋白（Albutein®，Grifols）的PE治疗，有三种不同的治疗方案：两次PE/周（三周），一次PE/周（六周），一次PE/双周（12周），加上六个月的随访期。测定血浆和脑脊液a - β1 - 40和a - β1 - 42水平，以及认知、功能和行为指标。结果：与基线相比，PE治疗组在最后一次PE后脑脊液Aβ1-42水平略高于对照组（调整后变异均值：75.3 vs -45.5 pg/mL; 95% CI: -19.8, 170.5 vs 135.1, 44.2; p = 0.072）。pe治疗组各治疗期血浆Aβ1-42水平均低于对照组（p < 0.05）。血浆a β1 - 40水平与PE呈锯齿状变化。在整个研究过程中，pe治疗的患者在波士顿命名测试和语义语言流畅性方面得分更高（p < 0.05）。PE期神经精神量表评分高于对照组（p < 0.05）。结论：PE与人白蛋白改变脑脊液和血浆Aβ1-42水平有关。接受PE治疗的患者表现出记忆力和语言功能的改善，这种改善在PE停用后仍持续存在。
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.