Meta-analysis: the efficacy of nootropic agent Cerebrolysin in the treatment of Alzheimer’s disease
First Online: 23 February 2007 Received: 01 September 2006 Accepted: 11 January 2007 DOI:
Cite this article as: Wei, ZH., He, QB., Wang, H. et al. J Neural Transm (2007) 114: 629. doi:10.1007/s00702-007-0630-y Summary.
To determine the therapeutic effect of nootropic agent Cerebrolysin on patients with mild to moderate Alzheimer’s disease (AD), we searched the Cochrane Library, Medline, PubMed, and Chinese Biomedical Literature Analysis and Retrieval System for Compact Disc (CBMDISC), and communicated with EBEWE Pharmaceutical Ltd, for randomized trials comparing Cerebrolysin with placebo in AD. Available data on clinical global impression, cognitive performance and activities of daily living were extracted from 6 randomized double-blind placebo-controlled clinical trials and combined with standard meta-analysis methods. An infusion with Cerebrolysin for 4 weeks (30 ml Cerebrolysin daily on five consecutive days of each week) led to a significant improvement of the clinical global impression. Compared with placebo, log(OR) was 1.1799, and 95% confident interval was 0.7463–1.6135 (
P < 0.05), indicating that Cerebrolysin could significantly improve the clinical global impression in patients with mild to moderate AD. However, more convincing evidences are needed for the efficacy of Cerebrolysin on the cognitive performance and activities of daily living. Keywords: Alzheimer’s disease, dementia, Cerebrolysin, neurotrophic therapy, clinical trials, meta-analysis References Alvarez, XA, Cacabelos, R, Laredo, M, Couceiro, V, Sampedro, C, Varela, M, Corzo, L, Fernandez-Novoa, L, Vargas, M, Aleixandre, M, Linares, C, Granizo, E, Muresanu, D, Moessler, H 2006 A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer’s disease Eur J Neurol 13 43 54 PubMed CrossRef Google Scholar Bae, CY, Cho, CY, Cho, K, Oh, BH, Choi, KG, Lee, HS, Jung, SP 2000 A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer’s disease J Am Geriatr Soc 48 1566 1571 PubMed Google Scholar Boado, RJ 2001 Amplification of blood–brain barrier GLUT1 glucose transporter gene expression by brain-derived peptides Neurosci Res 40 337 342 PubMed CrossRef Google Scholar Eder, P, Reinprecht, I, Schreiner, E, Skofitsch, G, Windisch, M 2001 Increased density of glutamate receptor subunit 1 due to Cerebrolysin treatment: an immunohistochemical study on aged rats Histochem J 33 605 612 PubMed CrossRef Google Scholar Frick, KM, Price, DL, Koliatsos, VE, Markowska, AL 1997 The effects of nerve growth factor on spatial recent memory in aged rats persist after discontinuation of treatment J Neurosci 17 2543 2550 PubMed Google Scholar Muresanu, DF, Rainer, M, Moessler, H 2002 Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin J Neural Transm Suppl 62 277 285 PubMed Google Scholar Normand, SLT 1999 Meta-analysis: formulating, evaluating, combining, and reporting Stat Med 18 321 359 PubMed CrossRef Google Scholar Panisset, M Gauthier, S Moessler, H Windisch, M Cerebrolysin Study Group 2002 Cerebrolysin in Alzheimer’s disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent J Neural Transm 109 1089 1104 PubMed CrossRef Google Scholar Rockenstein, E, Adame, A, Mante, M, Larrea, G, Crews, L, Windisch, M, Moessler, H, Masliah, E 2005 Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer’s disease with the neurotrophic compound cerebrolysin J Neural Transm 112 269 282 PubMed CrossRef Google Scholar Rockenstein, E, Torrance, M, Mante, M, Adame, A, Paulino, A, Rose, JB, Crews, L, Moessler, H, Masliah, E 2006 Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease J Neurosci Res 15 1252 1261 CrossRef Google Scholar Ruether, E, Rither, R, Apecechea, M, Freytag, S, Windisch, M 1994 Efficacy of the peptidergic nootropic drug Cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT) Pharmacopsychiatry 27 32 40 CrossRef Google Scholar Ruether, E, Ritter, R, Apecechea, M, Freytag, S, Gmeinbauer, R, Windisch, M 2000 Sustained improvements in patients with dementia of Alzheimer’s type (DAT) 6 months after termination of Cerebrolysin therapy J Neural Transm 107 815 829 CrossRef Google Scholar Ruether, E, Husmann, R, Kinzler, E, Diabl, E, Klingler, D, Spatt, J, Ritter, R, Schmidt, R, Taneri, Z, Winterer, W, Koper, D, Kasper, S, Rainer, M, Moessler, H 2001 A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patient with mild to moderate Alzheimer’s disease Int Clin Psychopharmacol 16 253 263 PubMed CrossRef Google Scholar Ruether, E, Alvarez, XA, Rainer, M, Moessler, H 2002 Sustained improvement of cognition and global function in patients with moderately severe AD: a double-blind, placebo-controlled study with the neurotrophic agent Cerebrolysin J Neural Transm Suppl 62 265 275 PubMed Google Scholar Seiger, A, Nordberg, A, von Holst, H, Backman, L, Ebendal, T, Alafuzoff, I, Amberla, K, Hartvig, P, Herlitz, A, Lilja, A 1993 Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy Behav Brain Res 57 255 261 PubMed CrossRef Google Scholar Whitehead, A 2002Meta-analysis of controlled clinical trial J Wiley Chichester Google Scholar Xiao, Sf, Yan, H, Yao, P 2000 Efficacy of FPF1070 (Cerebrolysin) in patients with Alzheimer’s disease: a multicenter, randomized, double-blind, placebo-controlled trial Clin Drug Invest 19 43 53 CrossRef Google Scholar