Efficacy of Cerebrolysin® in Alzheimer’s disease

  • E. Ruether
  • R. Ritter
  • M. Apecechea
  • S. Freitag
  • M. Windisch
Part of the Key Topics in Brain Research book series (KEYTOPICS)


Background. Alzheimer’s disease (AD) accounts for about half of all cases of senile dementia. Its prevelance increases steeply with age, from less than 1% at 60 to 15% in the 9th decade. The disease causes great suffering to patients and their families, and huge costs to society. Four million patients suffer from AD in the USA alone.

Cerebrolysin is a nootropic drug directly affecting cerebral neurons due to a unique neurotrophic activity. Positive effects are expected in AD.

Methods. A prospective, double-blind, placebo-controlled, randomized trial was conducted. 120 subjects with mild to moderate dementia were included. Either placebo i.v. or 30 ml Cerebrolysin i.v. were given daily Monday to Friday for four weeks. The results were assessed with scales including the Clinical Global Impression (CGI), the SCAG (Sandoz Clinical Assessment-Geriatric), a trail-making test (ZVT-G), a self-assessment test (Bf/S), and the NAA which measures the activities of daily living.

Results. Cerebrolysin-treated subjects demonstrated marked improvement which was both clinically relevant and statistically significant. The responder rate in the Cerebrolysin group was 61.7%. There were no side effects or drop-outs in either group.

Conclusions. Cerebrolysin leads to fast and clinically relevant improvement in AD.


Nerve Growth Factor Clinical Global Impression Senile Dementia Minor Improvement Neurobiol Aging 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alzheimer A (1907) Über die eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr 64:146.Google Scholar
  2. Alzheimer A (1911) Über eigenartige Krankheitsfälle des späteren Alters. Z Ges Neurol Psychiatr 4:356.CrossRefGoogle Scholar
  3. Akai F, Hiruma S, Sato T, Iwamoto N, Fujimoto M, Ioku M, Hashimoto S (1992) Neurotrophic factor-like effect of FPF 1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7:213–221.PubMedGoogle Scholar
  4. Albrecht E, Hingel S (1992) The effects of cerebrolysin on the vitality and sprouting of neurons from cerebral hemispheres and from the brain stem of chicken embryos in vitro. Neurobiol Aging 13 [Suppl 1]:S127.CrossRefGoogle Scholar
  5. Amaduccil, Angst J, Bech P, Benkert O, Bruinvels J, Engel RR, Gottfries CG, Hippius H, Levy R, Lingjaerde O, Lopez-Ibor JJ, Orgogozo JM, Pull Z, Saletu B, Stoll KD, Woggon B (1990) Consensus Conference on the methotholology of clinical trials of “Nootropics”, Munich, June, 1989. Pharmakopsychiatrie 23:171–175.CrossRefGoogle Scholar
  6. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, revised. Washington, DC.Google Scholar
  7. Arzneimittelinformation Berlin (1991) Komplikationen mit Todesfolge nach Rinderhirngangliosid GM1 (SYGEN) 1:8.Google Scholar
  8. Arzneimittelinformation Berlin (1994) “Aus” für Ginko biloba (TEBONIN)-Ampullen 4:39.Google Scholar
  9. Baskys A, Wojtowicz JN (1992) Actions of organ derived preperations on synaptic transmission in the hippocampus. Neurobiol Aging 13[Suppl 1]:128.CrossRefGoogle Scholar
  10. Bergerm A (1993) Estimation of concordance rate in demented twin pairs as a function of age of onset and age of sample. Psychiatr Gen 3:139.CrossRefGoogle Scholar
  11. Breitner J, Gatz M, Betgem Alm, Christian JC, Mortimer JA, Mcclearn GE (1991) Use of twin cohorts for research in Alzheimer’s disease. Neurology 43:261–267.Google Scholar
  12. Corder E, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923.PubMedCrossRefGoogle Scholar
  13. Davidson M, Stern RG, Bierer LM, Horvath TB, Zemishlani Z, Markofsky R, Mohs RC (1991) Cholinergic strategies in the treatment of Alzheimer’s disease. Acta Psychiatr Scand 366:47–51.CrossRefGoogle Scholar
  14. Davis D, Maloney AJ (1976) Selectiv loss of centrocholinergic neurons in Alzheimers’ disease. Lancet ii:1403–1405.CrossRefGoogle Scholar
  15. Davies P (1991) Therapy for Alzheimer’s disease: choosing a target. Clin Neuropharmacol 14:124–133.CrossRefGoogle Scholar
  16. Finali G, Piccirilli M, Oliani C, Piccinin LG (1991) Deprenyl therapy improves verbal memory in amnesic Alzheimer patients. Clin Neuropharmacol 14(6):523–536.PubMedCrossRefGoogle Scholar
  17. Folstein MF, Folstein SE, Huge BR MC (1975) Mini Mental State. A practical method for grating the cognitive state of patients for the clinician. J Psychiat Res 12:1989–1998.CrossRefGoogle Scholar
  18. Gauthier S, Gauthier L, Bouchard R, Quirion R, Sultan S (1991) Treatment of Alzheimer’s disease: hopes and reality. J Can Sci Neurol 18:439–441.Google Scholar
  19. Goate A, Chartier-Harlin MC, Mullan M (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706.PubMedCrossRefGoogle Scholar
  20. Guy W, Bonato RR (1970) Manual for the Ecdeu assessment battery, 2nd edn, revised. Chevy Chase, Maryland, 12:1–12.Google Scholar
  21. Hachinski VC, Iliff LD, Zilhka E, du Boulay GH, Allister VL, McMarshall J, Brussel RR, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637.PubMedCrossRefGoogle Scholar
  22. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62.PubMedCrossRefGoogle Scholar
  23. Hebenstreit GF (1986) Die Wirkung eines Aminosäure-Peptid-Extraktes bei zerebralen Funktionsstörungen in der Gerontopsychiatrie. Neuropsychiatrie 1(1):38–44.Google Scholar
  24. Hefti F, Schneider LS (1991) Nerve growth factor and Alzheimer’s disease. Clin Neuropharmacol 14:62–76.CrossRefGoogle Scholar
  25. Hefti F (1983) Alzheimer disease caused by a lack of nerve growth factor? Ann Neurol 13:109–110.PubMedCrossRefGoogle Scholar
  26. Heiss WD, Hebold I, Klinkhammer P, Ziffling P, Szelies B, Pawlik G, Herholz K (1988) Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by positron emission tomography. J Cereb Blood Flow Metab 8(4):613–617.PubMedCrossRefGoogle Scholar
  27. Hoyer S, Pöhlmann K, Hügel M (1992) Ätiopathogenese vaskulärer und degenerativer Demenzen — aktueller Kenntnisstand. Acta Histochem Su B 42:71–76.Google Scholar
  28. Jarvik LF (1991) Calcium channel blocker nimodipine for primary degenerative dementia. Biol Psychiatry 30:1171–1174.PubMedCrossRefGoogle Scholar
  29. Jorm AF, Corten AE, Henderson AS (1987) The prevalence of dementia: a quantitative integration of the literature. Acta Psychiat 76:465–479.CrossRefGoogle Scholar
  30. Kanowski S, Ladurner G, Maurer K, Oswald WD, Stein U (1990) Empfehlungen zur Evaluierung der Wirksamkeit von Nootropika. Z Gerontopsychol Gerontopsychiatr 3(1):67–79.Google Scholar
  31. Kofler B, Erhart C, Erhart P, Harrer G (1989) Zur therapeutischen Wirksamkeit von Cerebrolysin. Psycho 15(8):29–33.Google Scholar
  32. Kofler B, Erhart C, Erhart P, Harrer G (1990a) Die Brauchbarkeit der ereigniskorrelierten Negativität zum Nachweis therapeutischer Wirkungen von Nootropika am Beispiel von Cerebrolysin. Z EEG EMG 21:3145–3149.Google Scholar
  33. Kofler B, Erhart C, Erhart P, Harrer G (1990b) A multidimensional approach in testing nootripic drug effects (Cerebrolysin). Arch Gerontol Geriatr 10:129–140.PubMedCrossRefGoogle Scholar
  34. Kumar V, Calache M (1991) Treatment of Alzheimer’s disease with cholinergic drugs. Int J Clin Pharmacol Ther Toxicol 29:123–137.Google Scholar
  35. Mangoni A, Grassi MP, Frattola L, Piolti R, Bassi S, Motta A, Marcone A, Smirne S (1991) Effects of a Mao-B inhibitor in the treatment of Alzheimer disease. Eur Neurol 31:100–107.PubMedCrossRefGoogle Scholar
  36. Mann DMA, Yates PO, Marcyniuk B (1984) Monoaminergic neurotransmitter systems in Alzheimertype dementia and in senile dementia of Alzheimer type. Clin Neuroparhol 3:199–205.Google Scholar
  37. Molloy DW, Gordon H, Guyatt DB, Wilson MS, Duke R, Rees L, Singer J (1991) Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer’s disease. Can Med Assoc J 144:129–134.Google Scholar
  38. National Institute of Mental Health: Clinical Global Impression (1981, 1986) In: CIPS-Collegium Internationale Psychiatriae Scalarum (eds) Internationale Skalen für Psychiatrie. Beltz Test.Google Scholar
  39. Oswald WD, Fleischmann UM (1986) Nürnberger Altersinventar. NAI, Erlangen.Google Scholar
  40. Perry EK, Tomlinson BE, Blessed G, Bergman K, Bigson TH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2:1457–1459.PubMedCrossRefGoogle Scholar
  41. Piswanger A, Paier B, Windisch M (1990) Modulation of protein synthesis in a cell-free system from rat brain by cerebrolysin during development and aging. Amino Acids 651-657.Google Scholar
  42. Reisberg B, Ferris SH, De Leon MJ, Crook T (1982) An instrument for the assessment of primary degenerative dementia (PDD). Am J Psychiatry 139:1136–1139.PubMedGoogle Scholar
  43. Schoenberg B, et al (1987) Alzheimer’s disease and other dementing illnesses in a defined United States population: incidence rates and clinical features. Ann Neurol 22:724.PubMedCrossRefGoogle Scholar
  44. Shader R, Harmatz JS, Salzman C (1974) A new scale for clinical assessment on geriatric populations: Sandoz Clinical Assessment-Geriatric (SCAG). J Am Geriatr Soc 22(3):107–113.PubMedGoogle Scholar
  45. Shimazu S, Iwamoto N, Itoh T, Akasako A, Seki H, Fujimoto M (1991) Neurotrophic activity of cerebrolysin. Second International Springfield Symposium on Advantage in Alzheimer Therapy, Springfield, USA.Google Scholar
  46. Shimazu S, Tachikawa N, Iwamoto N, Itoh D, Komatsu S, Fujimoto M (1992) The neurotrophic and brain protective effect of cerebrolysin. Neurobiol Aging 13[Suppl 1]:50.Google Scholar
  47. Skoog I, Nilsson L, Palmertz B, Andreasson LA, Svanberg A (1993) A population based study of senile dementia in 85 year olds. N Engl J Med 328:153–158.PubMedCrossRefGoogle Scholar
  48. Suchanek-Fröhlich H, Wunderlich E (1986) Über die Wirksamkeit eines Aminosäure-Peptid-Extraktes — Randomisierte Doppelblind-Placebo-Vergleichsstudie. Neuropsychiatrie 1(1):45–48.Google Scholar
  49. Svennerholm L, Gottfries CG, Blennow K, Fredman P, Karlsson I, Mansson JE, Toffano G, Wallin A (1990) Parenteral administration of GM1 ganglioside to presenile Alzheimer patients. Acta Neurol Scand 81:48–53.PubMedCrossRefGoogle Scholar
  50. Travis J (1993) New piece in Alzheimer’s puzzle. Science 261:828–829.PubMedCrossRefGoogle Scholar
  51. Tuszynski MH, Gage FH (1990) Potential use of neurotrophic agents in the treatment of neurodegenerative disorders. Acta Neurobiol Ex 50:323–332.Google Scholar
  52. Vereshchagin N, Lebedeva NV, Suslina ZA, Solovyov OI, Priadov MA, Altunina MN (1991) Mild forms of multiinfarct dementia: effectiviness of cerebrolysin. Sowj Med (Moskau) 11:6–8.Google Scholar
  53. Windisch M, Piswanger A (1987) Einfluß einer 7tägigen Behandlung mit Cerebrolysin auf die Atmung von Hirnmitochondrien. Neuropsychiatrie 1(2):83–88.Google Scholar
  54. Zerssen D von, Möller H-J (1980) Psychopathometrische Verfahren in der psychiatrischen Therapieforschung. In: Bifang S (ed) Evaluations-Forschung in der Psychiatrie: Fragestellung und Methoden. Enke, Stuttgart.Google Scholar

Copyright information

© Springer-Verlag/Wien 1994

Authors and Affiliations

  • E. Ruether
    • 1
  • R. Ritter
    • 1
  • M. Apecechea
    • 1
  • S. Freitag
    • 1
  • M. Windisch
    • 2
  1. 1.Department of PsychiatryUniversity of Göttingen, School of MedicineGöttingenFederal Republic of Germany
  2. 2.Department of Research & DevelopmentEbewe Pharmaceuticals LtdUnterachAustria

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