Neuroscience and Behavioral Physiology

, Volume 40, Issue 8, pp 926–933

Efficacy of Akatinol Memantine in Moderate Cognitive Impairments

  • O. S. Levin
  • N. A. Yunishchenko
  • M. A. Dudarova
Article
  • 95 Downloads

A six-month open clinical trial of the efficacy of Akatinol was conducted in 40 patients with moderate cognitive impairments (MCI) using piracetam (20 patients) as reference agent; mean age was 67.7 ± 7.2 years. Patient status was evaluated using a number of scales, questionnaires, and neuropsychological tests prior to treatment and at three and six months of treatment. Akatinol was given at a dose of 10 mg/day, and 20 patients received piracetam at a dose of 1200 mg/day. Studies were completed by 38 patients (95%) in the Akatinol arm and 18 (90%) in the piracetam arm. In the group treated with Akatinol, 5% reported deterioration, 20% no change, 35% moderate improvement, 25% marked improvement, and 15% great improvement. In the Akatinol arm, the proportion of patients without effects was significantly lower, while the proportions of patients with marked and great improvements were significantly higher than in the piracetam arm. Overall evaluation of cognitive functions on the MMSE scale showed significant increases in both groups by the end of the third month, though only patients receiving Akatinol maintained the improvements to the end of the sixth month. Akatinol treatment also produced positive changes in the symptoms of depression, subjective symptoms, and quality of life. More marked positive changes were seen in the dysregulatory type of MCI than in the amnestic type of MCI. The concept of MCI with a high risk of transformation to dementia is introduced; in this situation, treatment with Akatinol may be particularly relevant.

Key words

moderate cognitive impairment dementia Akatinol memantine piracetam 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Zh. M. Glozman, Quantitative Evaluation of Neuropsychological Study Data [in Russian], Moscow (1999).Google Scholar
  2. 2.
    I. V. Damulin, “Mild cognitive impairments,” Consilium Medicum, No. 2, 138–141 (2004).Google Scholar
  3. 3.
    V. V. Zakharov and N. N. Yakhno, “Moderate cognitive impairments syndrome in the elderly: diagnosis and treatment,” Rus. Med. Zh., No. 10, 573–576 (2004).Google Scholar
  4. 4.
    O. S. Levin, “Diagnosis and treatment of moderate cognitive impairments in the elderly,” Zh. Nevrol. Psikhiat., No. 8, 42–49 (2006).Google Scholar
  5. 5.
    O. S. Levin and L. V. Golubeva, “Heterogeneity of moderate cognitive impairment: diagnostic and therapeutic aspects,” Consilium, No. 12, 106–110 (2006).Google Scholar
  6. 6.
    O. S. Levin, M. M. Sagova, and L. V. Golubeva, “Factors influencing quality of life in patients with cerebral ischemia with moderate cognitive impairment,” Rus. Med. Zh., No. 3, 25–29 (2006).Google Scholar
  7. 7.
    A. R. Luriya, Cortical Functions in Humans and Their Impairment in Local Brain Lesions [in Russian], Moscow State University, Moscow (1969).Google Scholar
  8. 8.
    A. Yu. Panasyuk, An Adapted Version of the Wechsler Scale [in Russian], Science Research Institute Psychiatry, Ministry of Health of the Russian Federation, Moscow (1983).Google Scholar
  9. 9.
    N. N. Yakhno and V. V. Zakharov, “Cognitive and emotional-affective impairments in cerebral ischemia,” Rus. Med. Zh., No. 10, 539–542 (2002).Google Scholar
  10. 10.
    P. Ahmed, J. Mitchell, and R. Arnold, “Rapid clinical progression in amnestic mild cognitive impairment,” Dement. Geriat. Cogn. Disord., 25, 170–177 (2008).CrossRefGoogle Scholar
  11. 11.
    L. G. Apostolova and J. L. Cummings, “Neuropsychiatric manifestations in mild cognitive impairment,” Dement. Geriat. Cogn. Disord., 25, 115–126 (2008).CrossRefGoogle Scholar
  12. 12.
    A. T. Beck, C. H. Ward, M. Mendelson, et al., “An inventory for measuring depression,” Arch. Gen. Psychiat., 4, 561–571 (1961).PubMedGoogle Scholar
  13. 13.
    R. Brooks, R. Rabin, and F. de Charro, The Measurement and Valuation of Health Status Using EQ-5D, Kluwer Academic Publishers, Dordrecht (2003).Google Scholar
  14. 14.
    S. DeKosky, J. Williamson, A. L. Fitzpatrick, et al., “Ginkgo biloba for prevention of dementia,” J. Amer. Med. Assoc., 300, 2253–2262 (2008).CrossRefGoogle Scholar
  15. 15.
    B. Dubois, H. Feldman, C. Jacova, et al., “Research criteria for the diagnosis of Alzheimer’s disease revising NINCDS-ADRDA criteria,” Lancet Neurology, 6, 734–746 (2007).CrossRefPubMedGoogle Scholar
  16. 16.
    K. Fassbender, M. Simons, C. Bergmann, et al., “Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo,” Proc. Natl. Acad. Sci. USA, 98, 5856–5861 (2001).CrossRefPubMedGoogle Scholar
  17. 17.
    H. H. Feldman, S. Ferris, B. Winblad, et al., “Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study,” Lancet Neurology, 6, 501–512 (2007).CrossRefPubMedGoogle Scholar
  18. 18.
    M. F. Folstein, S. E. Folstein, and P. R. McHugh, “Mini-mental status,” J. Psychiat. Res., 12, 189–196 (1975).CrossRefPubMedGoogle Scholar
  19. 19.
    F. Forette, M. Seux, J. Staessen, et al., “Prevention of dementia in Syst-Eur trail,” Lancet, 352, 1347–1351 (1998).CrossRefPubMedGoogle Scholar
  20. 20.
    P. T. Francis, “Behavioral effects of memantine: understanding the pharmacological rationale,” Eur. J. Neurosci., 14, Suppl. 1, 14 (1998).Google Scholar
  21. 21.
    S. Gauthier and J. Touchon, “Subclassification of mild cognitive impairment in research and in clinical practice,” Alzheimer’s Disease and Related Disorders Annual, 61–70 (2004).Google Scholar
  22. 22.
    S. Gauthier, Y. Wirth, and H. J. Mobius, “Effects of memantine on behavioral symptoms in Alzheimer disease patients,” Int. J. Geriat. Psychiat., 20, 459–464 (2005).CrossRefGoogle Scholar
  23. 23.
    R. K. Heaton, Wisconsin Card Sorting Test Manual, Psychological Assessment Resources, Odessa, FL (1981).Google Scholar
  24. 24.
    V. Jelic, M. Kivipelto, and B. Winblad, “Clinical trials in mild cognitive impairment: lessons for the future,” J. Neurol. Neurosurg. Psychiat., 77, 429–438 (2006).CrossRefPubMedGoogle Scholar
  25. 25.
    M. Kivipelto, E. L. Helkala, T. Hanninen, et al., “Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study,” Neurology, 56, 1683–1689 (2001).PubMedGoogle Scholar
  26. 26.
    S. Larrieu, L. Letenneur, J. M. Orgogozo, et al., “Incidence and outcome of mild cognitive impairment in a population-based prospective cohort,” Neurology, 59, 1594–1599 (2002).PubMedGoogle Scholar
  27. 27.
    H. Lehfield and H. Erzigkeit, “The SKT-A Short Cognitive Performance Test for Assessing Deficits of Memory and Attention,” Int. Psychogeriatrics, 9, 115–121 (1997).CrossRefGoogle Scholar
  28. 28.
    L. Li, A. Sengupta, N. Haque, et al., “Memantine inhibits and reverses the Alzheimer’s type abnormal hyperphosphorylation of tau and associated neurodegeneration,” FEBS Lett., 566, 261–269 (2004).CrossRefPubMedGoogle Scholar
  29. 29.
    P. J. Manos and R. Wu, “The ten point clock test,” Int. J. Psychiat. Med., 24, 229–244 (1994).CrossRefGoogle Scholar
  30. 30.
    B. McGuiness, S. Todd, A. P. Passmore, et al., “Systematic review: blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia,” J. Neurol. Neurosurg. Psychiat., 79, 4–5 (2008).CrossRefGoogle Scholar
  31. 31.
    M. A. Mintun, G. N. Larossa,Y. I. Sheine, et al., “[11C]PIB in a non-demented population: potential antecedent marker of Alzheimer disease,” Neurology, 67, 446–452 (2006).CrossRefPubMedGoogle Scholar
  32. 32.
    A. J. Mitchell and M. Shiri-Feshki, “Temporal trends in the long term risk of progression of mild cognitive impairment: a pooled analysis,” J. Neurol. Neurosurg. Psychiat., 79, 1386–1391 (2008).CrossRefPubMedGoogle Scholar
  33. 33.
    A. J. Mitchell and M. Shiri-Feshki, “Rate of progression of mild cognitive impairment to dementia,” Acta Psychiat. Scand., DOI:10.1111/j.1600-0447.2008.01326.x (2009).
  34. 34.
    P. J. Mondrego and J. Fernandez, “Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study,” Arch. Neurol., 61, 1290–1293 (2004).CrossRefGoogle Scholar
  35. 35.
    J. C. Morris and J. Cummings, “Mild cognitive impairment (MCI) represents early-stage Alzheimer’s disease,” J. Alzheimer’s Dis., 7, 235–239 (2005).Google Scholar
  36. 36.
    J. M. Orgogozo, A. S. Rigaud, A. Stöffer, et al., “Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300),” Stroke, 33, 1834–1839 (2002).CrossRefPubMedGoogle Scholar
  37. 37.
    K. Palmer, A. K. Berger, R. Monastero, et al., “Predictors of progression from mild cognitive impairment to Alzheimer disease,” Neurology, 68, 1596–1602 (2007).CrossRefPubMedGoogle Scholar
  38. 38.
    E. R. Peskind, S. G. Potkin, N. Pomara et al., “Memantine treatment in mild to moderate Alzheimer’s disease,” Am. J. Geriat. Psychiat., 14, 704–715 (2006).CrossRefGoogle Scholar
  39. 39.
    R. C. Peterson, G. E. Smith, S. C. Waring, et al., “Mild cognitive impairment: clinical characterization and outcome,” Arch. Neurol., 56, 303–308 (1999).CrossRefGoogle Scholar
  40. 40.
    R. C. Petersen, R. Doody, A. Kurz, et al., “Current concepts in mild cognitive impairment,” Arch. Neurol., 58, 1985–1992 (2001).CrossRefPubMedGoogle Scholar
  41. 41.
    R. C. Petersen, J. C. Stevens, M. Ganguli, et al., “Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology,” Neurology, 56, 1133–1142 (2001).PubMedGoogle Scholar
  42. 42.
    R. C. Petersen, R. G. Thomas, M. Grundman, et al., “Vitamin E and donepezil for the treatment of mild cognitive impairment,” N. Eng. J. Med., 352, 2379–2388 (2005).CrossRefGoogle Scholar
  43. 43.
    F. Portet, P. J. Ousset, P. J. Visser, et al., “Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer’s Disease,” J. Neurol. Neurosurg. Psychiat., 77, 714–718 (2006).CrossRefPubMedGoogle Scholar
  44. 44.
    B. Reisberg, R. Doody, A. Stoffler, et al., “Memantine in moderate-tosevere Alzheimer’s disease,” N. Eng. J. Med., 348, 1333–1341 (2003).CrossRefGoogle Scholar
  45. 45.
    D. R. Royall, “Executive cognitive impairment: a novel perspective on dementia,” Neuroepidemiology, 19, 293–299 (2000).CrossRefPubMedGoogle Scholar
  46. 46.
    S. Salloway, S. Ferris, A. Kluger, et al., “Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial,” Neurology, 63, 651–657 (2004).PubMedGoogle Scholar
  47. 47.
    M. Sarazin, C. Berr, and J. de Rotrou, “Amnestic syndrome of the medial temporal type identifies prodromal AD,” Neurology, 69, 1859–1867 (2007).CrossRefPubMedGoogle Scholar
  48. 48.
    P. Seeman, C. Caruso, and M. Lasaga, “Memantine agonist action at dopamine d2high receptors,” Synapse, 62, 149–153 (2008).CrossRefPubMedGoogle Scholar
  49. 49.
    R. Spanagel, B. Eilbacher, and R. Wilke, “Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat – a pharmacokinetic microdialysis study,” Eur. J. Pharmacol., 262, 21–26 (1994).CrossRefPubMedGoogle Scholar
  50. 50.
    S. E. Starkstein, H. S. Mayberg, T. J. Preziosi, et al., “Reliability, validity, and clinical correlates of apathy in Parkinson’s disease,” J. Neuropsychiat. Clin. Neurosci., 4, 134–139 (1992).Google Scholar
  51. 51.
    P. T. Tariot, M. R. Farlow, G. R. Grossberg, et al., “Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial,” J. Am. Med. Assoc., 291, 317–324 (2004).CrossRefGoogle Scholar
  52. 52.
    B. Winblad, R. Jones, Y. Wirth, et al., “Memantine in moderate to severe Alzheimer’s disease: meta-analysis of randomized clinical trials,” Dement. Geriat. Cogn. Disord., 24, 20–27 (2007).CrossRefGoogle Scholar
  53. 53.
    B. Winblad, S. Gauther, L. Scinto, et al., “Safety and efficacy of galantamine in subjects with mild cognitive impairment,” Neurology, 70, 2024–2035 (2008).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2010

Authors and Affiliations

  • O. S. Levin
    • 1
  • N. A. Yunishchenko
    • 1
  • M. A. Dudarova
    • 1
  1. 1.Department of NeurologyRussian Postgraduate Medical AcademyMoscowRussia

Personalised recommendations