用脑蛋白水解物和多奈哌齐治疗的阿尔茨海默病患者血清脑源性神经营养因子的协同增加：与载脂蛋白E4病例认知改善的关联
Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases.
作者信息
Alvarez X Anton, Alvarez Irene, Iglesias Olalla, Crespo Ignacio, Figueroa Jesus, Aleixandre Manuel, Linares Carlos, Granizo Elias, Garcia-Fantini Manuel, Marey Jose, Masliah Eliezer, Winter Stefan, Muresanu Dafin, Moessler Herbert
机构信息
Medinova Institute of Neurosciences, Clinica RehaSalud, A Coruña, Spain (Dr Alvarez, Ms Alvarez, Ms Iglesias, Mr Crespo, and Dr Figueroa); Clinical Research Department, QPS Holdings, A Coruña, Spain (Dr Alvarez); Rehabilitation Department, Hospital Clinico Universitario, Santiago de Compostela, Spain (Dr Figueroa); School of Psychology, Granada University, Granada, Spain (Dr Aleixandre); Complejo Asistencial HHSCJ, Málaga, Spain (Drs Linares and Granizo); Department of Neurosurgery, Hospital HM Modelo, A Coruña, Spain (Dr Garcia-Fantini); Department of Neurology, Hospital Clinico Universitario, A Coruña, Spain (Dr Marey); Departments of Neurosciences and Pathology, School of Medicine, University of California San Diego, La Jolla, CA (Dr Masliah); Ever NeuroPharma, Unterach, Austria (Drs Winter and Moessler); Department of Clinical Neurosciences, University of Medicine and Pharmacy "Iuliu Hațieganu", Cluj-Napoca, Romania (Dr Muresanu); and ''RoNeuro'' Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (Dr Muresanu).
出版信息
Int J Neuropsychopharmacol. 2016 Jun;19(6). doi: 10.1093/ijnp/pyw024. Epub 2016 Apr 7.
BACKGROUND
Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer's disease.
METHODS
We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer's disease patients.
RESULTS
Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy.
CONCLUSION
Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer's disease cases with apolipoprotein E epsilon-4 allele.
背景
循环中脑源性神经营养因子水平低可能会促进认知功能衰退，但神经营养疗法和联合药物疗法对阿尔茨海默病患者血清脑源性神经营养因子的影响此前尚未得到研究。
方法
我们评估了脑蛋白水解物、多奈哌齐以及联合疗法对轻至中度阿尔茨海默病患者在第16周（脑蛋白水解物治疗结束时）和第28周（研究终点）时血清脑源性神经营养因子水平的影响。
结果
在第16周时，脑蛋白水解物可提高血清脑源性神经营养因子水平，而多奈哌齐则无此作用；联合疗法在第16周和研究终点时均能提高该水平。联合疗法组在第16周和第28周时脑源性神经营养因子的反应分别显著高于多奈哌齐组和脑蛋白水解物组。载脂蛋白Eε4等位基因携带者的脑源性神经营养因子升高幅度更大，在接受脑蛋白水解物和联合疗法治疗的载脂蛋白Eε4等位基因患者中，较高的脑源性神经营养因子水平与更好的认知改善相关。
结论
我们的结果表明，脑蛋白水解物和多奈哌齐具有协同作用，可提高血清脑源性神经营养因子水平并延缓认知衰退，尤其是在携带载脂蛋白Eε4等位基因的阿尔茨海默病患者中。
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