Combination treatment in Alzheimer's disease: Results of a randomized, controlled trial with cerebrolysin and donepezil

Current Alzheimer Research

Volumn 8, Issue 5, 2011, Pages 583-591

  Alvarez, X A ^a   Cacabelos, R ^a   Sampedro, C ^a   Couceiro, V ^a   Aleixandre, M ^b   Vargas, M ^b   Linares, C ^c   Granizo, E ^c   Garcia Fantini M ^d   Baurecht, W ^e   Doppler, E ^f   Moessler, H ^f  

^a Centro de Investigacion Biomedica EuroEspes   (Spain)

^b Geroclinic   (Spain)

^c Memory Clinic   (Spain)

^d HOSPITAL JUAN CANALEJO   (Spain)

^e acromion GmbH   (Germany)

^f EVER Neuro Pharma GmbH   (Austria)

Author keywords

Alzheimer's disease; Cerebrolysin; Combination therapy; Donepezil; Neurotrophic factor; Randomized controlled trial

Indexed keywords

ACETYLSALICYLIC ACID; ALPRAZOLAM; CEREBROLYSIN; CITICOLINE; DONEPEZIL;

AGED; AGGRESSION; AGITATION; ALZHEIMER DISEASE; ANOREXIA; ANXIETY; ARTICLE; CONFUSION; CONTROLLED STUDY; DAILY LIFE ACTIVITY; DELUSION; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; DYSPEPSIA; DYSTHYMIA; FEMALE; HUMAN; HYPOKINESIA; INSOMNIA; MAJOR CLINICAL STUDY; MALE; MENTAL PERFORMANCE; MINI MENTAL STATE EXAMINATION; MULTICENTER STUDY; MUSCLE SPASM; NAUSEA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; TREATMENT DURATION; TREATMENT OUTCOME; URINARY TRACT INFECTION;

ACTIVITIES OF DAILY LIVING; AGED; ALZHEIMER DISEASE; AMINO ACIDS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INDANS; MALE; NEUROPROTECTIVE AGENTS; NEUROPSYCHOLOGICAL TESTS; PIPERIDINES; TREATMENT OUTCOME;

EID: 79960016354     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/156720511796391863     Document Type: Article

References (33)

1. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer's disease. Am J Med 120: 388-397 (2007).
2. Cortes F, Portet F, Touchon J, Vellas B. Six and 18-month changes in mild to moderate Alzheimer's patients treated with acetylcho-linesterase inhibitors: what can we learn for clinical outcomes of therapeutic trials? J Nutr Health Aging 11: 330-337 (2007).
3. Akai F, Hiruma S, Sato T, Iwamoto N, Fujimoto M, Ioku M, et al. Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7: 213-221 (1992).
4. Satou T, Itoh T, Fujimoto M, Hashimoto S. Neurotrophic-like effects of FPF-1070 on cultured neurons from chick embryonic dorsal root ganglia. Jpn Pharmacol Ther 22: 205-212 (1994).
5. Alvarez XA, Sampedro C, Cacabelos R, Linares C, Aleixandre M, García-Fantini M, et al. Reduced TNF-alpha and increased IGF-I levels in the serum of Alzheimer patients treated with the neurotro-phic agent Cerebrolysin. Int J Neuropsychopharmacol 12: 867-872 (2009).
6. Alvarez XA, Lombardi V, Fernández-Novoa L, García M, Sanpedro C, Cagiao A, et al. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm 59: 281-292 (2000).
7. Masliah E, Armasolo F, Veinbergs I, Mallory M, Samuel W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Behav 62: 239-245 (1999).
8. Reinprecht I, Gschanes A, Windisch M, Fachbach G. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats. Histochem J 31: 395-401 (1999).
9. Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, et al. Cerebrolysin decreases amyloid-beta production by regulating amyloid precursor protein maturation in a transgenic model of Alzheimer's disease. J Neurosci Res 83: 1252-1261 (2006).
10. Chen H, Tung YC, Li B, Iqbal K, Grundke-Iqbal I. Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogene-sis. Neurobiol Aging 28: 1148-1162 (2007).
11. Rockenstein E, Mante M, Adame A, Crews L, Moessler H, Masliah E. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer's disease. Acta Neuropathol 113: 265-275 (2007).
12. Alvarez XA, Cacabelos R, Laredo M, Couceiro V, Sanpedro C, Varela M, et al. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's Disease. Eur J Neurology 13: 46-54 (2006).
13. Bae CY, Cho CY, Cho K, Hoon Oh B, Choi KG, Lee HS, et al. A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease. J Am Geriatr Soc 48: 1566-1571 (2000).
14. Panisset M, Gauthier S, Moessler H, Windisch M. Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm 109: 1089-1104 (2002).
15. Ruether E, Husmann R, Kinzler E, Diabl E, Klingler D, Spatt J, et al. A 28-week, double-blind, placebo-controlled study with Cere-brolysin in patients with mild to moderate Alzheimer's disease. Int Clin Psychopharmacol 16: 253-263 (2001).
16. Ginsberg SD, Wuu J, Counts SE, Mufson EJ. Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimeŕs disease. J Neurochem 97: 475-487 (2006).
17. Mufson EJ, Counts SE, Fahnestock M, Ginsberg SD. Cholinotro-phic molecular substrates of mild cognitive impairment in the elderly. Curr Alzheimer Res 4: 340-350 (2007).
18. Fumagalli F, Racagni G, Riva MA. The expanding role of BDNF: a therapeutic target for Alzheimer's disease? Pharmacogenomics J 6: 8-15 (2006).
19. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198 (1975).
20. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry 141: 1356-1364 (1984).
21. Mohs RC, Knopman D, Petersen RC, Ferris SH, Ernesto C, Grundman M, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope: The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 11: S13-21 (1997).
22. Knopman DS, Knapp MJ, Gracon SI, Davis CS. The Clinician Interview-Based Impression (CIBI): a clinician's global change rating scale in Alzheimer's disease. Neurology 44: 2315-2321 (1994).
23. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 11: S33-39 (1997).
24. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44: 2308-2314 (1994).
25. Bauer P. Multiple Testing in Clinical Trials. Stat Med 10: 871-89; discussion 889-890 (1991).
26. Chi GYH. Multiple Testings: Multiple Comparisons and Multiple Endpoints. Drug Inf J 32: 1347S-1362S (1998).
27. Rogers SL, Farlow MR, Doody RS. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology 50: 136-145 (1998).
28. Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Möller HJ, et al. The effects of Donepezil in Alzheimeŕs disease-results from a Multinational Trial. Dement Geriatr Cogn Disord 10: 237-244 (1999).
29. Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, et al. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 57: 481-488 (2001).
30. Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, et al. A 1-year, randomized, placebo-controlled study of donepe-zil in patients with mild to moderate AD. Neurology 57: 489-495 (2001).
31. Cummings JL, McRae T, Zhang R, Donepezil-Sertraline Study Group. Effects of Donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. Am J Geriatr Psychiatry 14: 605-612 (2006).
32. Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimeŕs disease. Int Psychogeriatr 14: 389-404 (2002).
33. Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, Bakay R, et al. A phase 1 clinical trial of nerve growth factor therapy for Alzheimer disease. Nat Med 11: 551-555 (2005).