Skip to main content
NCBI home page
Journal of Psychiatry & Neuroscience: JPN logoLink to Journal of Psychiatry & Neuroscience: JPN
. 1999 May;24(3):234–243.

Selegiline in the treatment of Alzheimer's disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group.

V Filip 1, E Kolibás 1
PMCID: PMC1189014  PMID: 10354658

Abstract

OBJECTIVE: To evaluate the efficacy and adverse effects of the type B monoamine oxidase inhibitor selegiline (also known as I-deprenyl) in the treatment of Alzheimer's disease. DESIGN: Long-term, double-blind, placebo-controlled trial. SETTING: Seven cities (1 or 2 nursing homes in each city) in the Czech and Slovak Republics. PATIENTS: A total of 173 nursing-home residents fulfilling the DSM-III criteria for mild to moderate Alzheimer's disease. INTERVENTIONS: Selegiline (10 mg per day) or placebo (both including 50 mg ascorbic acid) administered for 24 weeks. OUTCOME MEASURES: Clinical Global Impressions scale and Nurses Observation Scale for Inpatient Evaluation at baseline and at weeks 6, 12 and 24; Clock Drawing Test at baseline and 24 weeks, results of which were evaluated as normal or pathologic, and quantitatively on a modified 6-point scale; Sternberg's Memory Scanning test at baseline and at weeks 6, 12 and 24; Mini Mental State Examination, and electroencephalogram at baseline and 24 weeks; Structured Adverse Effects Rating Scale; physical, laboratory, hematological and electrocardiographic examinations at baseline and weeks 12 and 24. RESULTS: A total of 143 subjects completed enough of the trial to be entered in the analysis. Subjects were analyzed by 2 subgroups depending on whether they had a normal or pathologic result of the Clock Drawing Test. Analysis of variance showed significant improvement with selegiline versus placebo among those with a normal result of the Clock Drawing Test on the Mini Mental Status Examination (total score and orientation-place subscale) and among those with a pathologic result of the Clock Drawing Test of Sternberg's Memory Scanning test (for both speed and accuracy), on the Clinical Global Impressions scale as well as in terms of the dominant frequency on electroencephalograms. CONCLUSION: Selegiline has a long-term beneficial effect in Alzheimer's disease on memory modalities that reflect the function of the prefrontal areas of the brain, which are rich in dopamine receptors. The delayed appearance of differences between selegiline and placebo supports the notion that the mechanism of action is through neuronal rescue or neuroprotection. The differential response of patients with normal and pathologic results of the Clock Drawing Test may reflect the fact that the evaluation methods' sensitivity to change depends on the severity of dementia.

Full text

PDF
234

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burke W. J., Roccaforte W. H., Wengel S. P., Bayer B. L., Ranno A. E., Willcockson N. K. L-deprenyl in the treatment of mild dementia of the Alzheimer type: results of a 15-month trial. J Am Geriatr Soc. 1993 Nov;41(11):1219–1225. doi: 10.1111/j.1532-5415.1993.tb07306.x. [DOI] [PubMed] [Google Scholar]
  2. Danielczyk W., Streifler M., Konradi C., Riederer P., Moll G. Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia. Acta Psychiatr Scand. 1988 Dec;78(6):730–736. doi: 10.1111/j.1600-0447.1988.tb06412.x. [DOI] [PubMed] [Google Scholar]
  3. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  4. Freedman M., Rewilak D., Xerri T., Cohen S., Gordon A. S., Shandling M., Logan A. G. L-deprenyl in Alzheimer's disease: cognitive and behavioral effects. Neurology. 1998 Mar;50(3):660–668. doi: 10.1212/wnl.50.3.660. [DOI] [PubMed] [Google Scholar]
  5. Funahashi S., Bruce C. J., Goldman-Rakic P. S. Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas". J Neurosci. 1993 Apr;13(4):1479–1497. doi: 10.1523/JNEUROSCI.13-04-01479.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldman-Rakic P. S., Lidow M. S., Smiley J. F., Williams M. S. The anatomy of dopamine in monkey and human prefrontal cortex. J Neural Transm Suppl. 1992;36:163–177. doi: 10.1007/978-3-7091-9211-5_8. [DOI] [PubMed] [Google Scholar]
  7. Hachinski V. C., Iliff L. D., Zilhka E., Du Boulay G. H., McAllister V. L., Marshall J., Russell R. W., Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975 Sep;32(9):632–637. doi: 10.1001/archneur.1975.00490510088009. [DOI] [PubMed] [Google Scholar]
  8. Iwasaki Y., Ikeda K., Shiojima T., Kobayashi T., Tagaya N., Kinoshita M. Deprenyl enhances neurite outgrowth in cultured rat spinal ventral horn neurons. J Neurol Sci. 1994 Aug;125(1):11–13. doi: 10.1016/0022-510x(94)90235-6. [DOI] [PubMed] [Google Scholar]
  9. Knoll J. The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl. Mech Ageing Dev. 1988 Dec;46(1-3):237–262. doi: 10.1016/0047-6374(88)90128-5. [DOI] [PubMed] [Google Scholar]
  10. Lawlor B. A., Aisen P. S., Green C., Fine E., Schmeïdler J. Selegiline in the treatment of behavioural disturbance in Alzheimer's disease. Int J Geriatr Psychiatry. 1997 Mar;12(3):319–322. doi: 10.1002/(sici)1099-1166(199703)12:3<319::aid-gps488>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  11. Mangoni A., Grassi M. P., Frattola L., Piolti R., Bassi S., Motta A., Marcone A., Smirne S. Effects of a MAO-B inhibitor in the treatment of Alzheimer disease. Eur Neurol. 1991;31(2):100–107. doi: 10.1159/000116655. [DOI] [PubMed] [Google Scholar]
  12. Martini E., Pataky I., Szilágyi K., Venter V. Brief information on an early phase-II study with deprenyl in demented patients. Pharmacopsychiatry. 1987 Nov;20(6):256–257. doi: 10.1055/s-2007-1017117. [DOI] [PubMed] [Google Scholar]
  13. Mytilineou C., Radcliffe P., Leonardi E. K., Werner P., Olanow C. W. L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro. J Neurochem. 1997 Jan;68(1):33–39. doi: 10.1046/j.1471-4159.1997.68010033.x. [DOI] [PubMed] [Google Scholar]
  14. Müller T., Kuhn W., Krüger R., Przuntek H. Selegiline as immunostimulant--a novel mechanism of action? J Neural Transm Suppl. 1998;52:321–328. doi: 10.1007/978-3-7091-6499-0_33. [DOI] [PubMed] [Google Scholar]
  15. Piccinin G. L., Finali G., Piccirilli M. Neuropsychological effects of L-deprenyl in Alzheimer's type dementia. Clin Neuropharmacol. 1990 Apr;13(2):147–163. doi: 10.1097/00002826-199004000-00004. [DOI] [PubMed] [Google Scholar]
  16. Salo P. T., Tatton W. G. Deprenyl reduces the death of motoneurons caused by axotomy. J Neurosci Res. 1992 Feb;31(2):394–400. doi: 10.1002/jnr.490310223. [DOI] [PubMed] [Google Scholar]
  17. Sano M., Ernesto C., Thomas R. G., Klauber M. R., Schafer K., Grundman M., Woodbury P., Growdon J., Cotman C. W., Pfeiffer E. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216–1222. doi: 10.1056/NEJM199704243361704. [DOI] [PubMed] [Google Scholar]
  18. Schneider L. S., Olin J. T., Pawluczyk S. A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in Alzheimer's disease. Am J Psychiatry. 1993 Feb;150(2):321–323. doi: 10.1176/ajp.150.2.321. [DOI] [PubMed] [Google Scholar]
  19. Sternberg S. High-speed scanning in human memory. Science. 1966 Aug 5;153(3736):652–654. doi: 10.1126/science.153.3736.652. [DOI] [PubMed] [Google Scholar]
  20. Stoll S., Hafner U., Pohl O., Müller W. E. Age-related memory decline and longevity under treatment with selegiline. Life Sci. 1994;55(25-26):2155–2163. doi: 10.1016/0024-3205(94)00396-3. [DOI] [PubMed] [Google Scholar]
  21. Sunderland T., Tariot P. N., Cohen R. M., Newhouse P. A., Mellow A. M., Mueller E. A., Murphy D. L. Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer's disease. Psychopharmacology (Berl) 1987;91(3):293–296. doi: 10.1007/BF00518180. [DOI] [PubMed] [Google Scholar]
  22. Tariot P. N., Cohen R. M., Sunderland T., Newhouse P. A., Yount D., Mellow A. M., Weingartner H., Mueller E. A., Murphy D. L. L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition. Arch Gen Psychiatry. 1987 May;44(5):427–433. doi: 10.1001/archpsyc.1987.01800170041007. [DOI] [PubMed] [Google Scholar]
  23. Tatton W. G., Chalmers-Redman R. M. Modulation of gene expression rather than monoamine oxidase inhibition: (-)-deprenyl-related compounds in controlling neurodegeneration. Neurology. 1996 Dec;47(6 Suppl 3):S171–S183. doi: 10.1212/wnl.47.6_suppl_3.171s. [DOI] [PubMed] [Google Scholar]
  24. Tomlinson B. E., Blessed G., Roth M. Observations on the brains of demented old people. J Neurol Sci. 1970 Sep;11(3):205–242. doi: 10.1016/0022-510x(70)90063-8. [DOI] [PubMed] [Google Scholar]
  25. Wolf-Klein G. P., Silverstone F. A., Levy A. P., Brod M. S. Screening for Alzheimer's disease by clock drawing. J Am Geriatr Soc. 1989 Aug;37(8):730–734. doi: 10.1111/j.1532-5415.1989.tb02234.x. [DOI] [PubMed] [Google Scholar]
  26. Wu R. M., Mohanakumar K. P., Murphy D. L., Chiueh C. C. Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline). Ann N Y Acad Sci. 1994 Nov 17;738:214–221. doi: 10.1111/j.1749-6632.1994.tb21806.x. [DOI] [PubMed] [Google Scholar]
  27. de la Cruz C. P., Revilla E., Steffen V., Rodríguez-Gómez J. A., Cano J., Machado A. Protection of the aged substantia nigra of the rat against oxidative damage by (-)-deprenyl. Br J Pharmacol. 1996 Apr;117(8):1756–1760. doi: 10.1111/j.1476-5381.1996.tb15350.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Psychiatry and Neuroscience are provided here courtesy of Canadian Science Publishing

RESOURCES