title: Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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). anton.alvarez@medinova.es.
authors.forename: X Anton
authors.initials: XA
authors.lastname: Alvarez
authors.affiliation: 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).
authors.forename: Irene
authors.initials: I
authors.lastname: Alvarez
authors.affiliation: 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).
authors.forename: Olalla
authors.initials: O
authors.lastname: Iglesias
authors.affiliation: 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).
authors.forename: Ignacio
authors.initials: I
authors.lastname: Crespo
authors.affiliation: 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).
authors.forename: Jesus
authors.initials: J
authors.lastname: Figueroa
authors.affiliation: 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).
authors.forename: Manuel
authors.initials: M
authors.lastname: Aleixandre
authors.affiliation: 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).
authors.forename: Carlos
authors.initials: C
authors.lastname: Linares
authors.affiliation: 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).
authors.forename: Elias
authors.initials: E
authors.lastname: Granizo
authors.affiliation: 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).
authors.forename: Manuel
authors.initials: M
authors.lastname: Garcia-Fantini
authors.affiliation: 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).
authors.forename: Jose
authors.initials: J
authors.lastname: Marey
authors.affiliation: 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).
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: 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).
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.affiliation: 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).
authors.forename: Dafin
authors.initials: D
authors.lastname: Muresanu
authors.affiliation: 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).
authors.forename: Herbert
authors.initials: H
authors.lastname: Moessler
keywords: Alzheimer’s disease; Cerebrolysin; apolipoprotein E epsilon-4 allele; brain derived neurotrophic factor; combination therapy