Psychopharmacology

, Volume 129, Issue 3, pp 285–288 | Cite as

The ability of THA treatment to increase cortical alpha waves is related to apolipoprotein E genotype of Alzheimer disease patients

  • Paavo Riekkinen
  • Hilkka Soininen
  • Juhani Partanen
  • Ari Pääkkönen
  • Seppo Helisalmi
  • Paavo Riekkinen
Original Investigation

Abstract

In a previous study, we reported that Alzheimer disease (AD) patients with an apolipoprotein E (APOE) ɛ4 allele (+ APOE4) show more severe loss of nucleus basalis (NB) cholinergic cells than patients without ɛ4 alleles (− APOE4). The present study investigates the effects of a single oral administration of THA 25 or 50 mg on cortical spectral EEG activity in + (five APOE4/4, six APOE4/3) and − APOE4 (eight APOE3/3) AD patients. THA 25 mg had no significant effect on EEG activity in any AD patients. However, THA 50 mg increased alpha activity and alpha/theta ratio in − APOE4 patients. In contrast, THA 50 mg had no effect on EEG activity in + APOE4 patients. This result tentatively suggests that in AD patients APOE genotype may affect the response of cortical electrical arousal to cholinergic therapy that enhances the efficacy of presynaptic NB axons.

Key words

THA EEG slowing Apolipoprotein E Alzheimer disease 

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References

  1. Alhainen K, Partanen J, Reinikainen K, Laulumaa V, Soininen H, Airaksinen M, Riekkinen P (1991) Discrimination of tetrahy-droaminoacridine responders by a single dose pharmaco-EEG in patients with Alzheimer’s disease. Neurosci Lett 127:113–116PubMedCrossRefGoogle Scholar
  2. Björklund M, Jäkälä P, Schmidt B, Riekkinen M, Koivisto E, Riekkinen P Jr (1996) An indirect Cholinesterase inhibitor, metrifonate, increases neocortical EEG arousal in rats. NeuroReport (in press)Google Scholar
  3. Corder EH, 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: 921–923PubMedCrossRefGoogle Scholar
  4. Davis KL, Thal LJ, Gamzu ER, Davis SC, Woolfson RF, Gracon SI, Drachman DA, Schneider LS, Whitehouse P, Hoover TM, Morris JC, Kawas CH, Knopman DS, Earl NL, Kumar V, Doody R, Tacrine Collaborative Study Group (1992) A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease. N Engl J Med 327:1253–1259PubMedGoogle Scholar
  5. Gustafson L, Edwinson L, Dahlgren N (1987) Intravenous physostigmine treatment of Alzheimer’s disease evaluated by psychometric testing, regional cerebral blood flow (rCBF) measurement and EEG. Psychopharmacology 93:31–35PubMedCrossRefGoogle Scholar
  6. Helkala E-L, Koivisto K, Hänninen T, Vanhanen M, Kervinen K, Kuusisto J, Mykkänen L, Kesäniemi YA, Laakso M, Riekkinen P Sr (1996) Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neurosci Lett 204:177–180PubMedCrossRefGoogle Scholar
  7. Nuwer MR (1988) Quantitative EEG: techniques and problems of frequency analysis and topographic mapping. J Clin Neurophysiol 5:1–43PubMedCrossRefGoogle Scholar
  8. Poirier J (1994) Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease. Trends Neurosci 17:525–530PubMedCrossRefGoogle Scholar
  9. Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K (1995) Apolipoprotein E, dementia, and cortical deposition of B-amy-loid protein. N Engl J med 333:1242–1247PubMedCrossRefGoogle Scholar
  10. Reinikainen KJ, Riekkinen P, Paljärvi L, Soininen H, Heikala E-L, Jolkkonen J, Laakso M (1988) Cholinergic deficit in Alzheimer’s disease: a study based on autopsy and CSF data. Neurochem Res 13:135–146PubMedCrossRefGoogle Scholar
  11. Riekkinen P, Buzsäki G, Riekkinen P Jr, Soininen H, Partanen J (1991) The cholinergic system and EEG slow waves. Electroencephalogr Clin Neurophysiol 78:89–96PubMedCrossRefGoogle Scholar
  12. Riekkinen P Jr, Sirviö J, Riekkinen M, Riekkinen P Sr (1991a) Effects of THA on passive avoidance retention performance of intact, nucleus basalis, frontal cortex and nucleus basalis + frontal — lesioned rats. Pharmacol Biochem Behav 39: 841–846PubMedCrossRefGoogle Scholar
  13. Riekkinen P Jr, Sirviö J, Valjakka A, Riekkinen M, Lammintausta R, Riekkinen P (1991b) Effects of alpha2 antagonists and an agonist on EEG slowing induced by scopolamine and lesion of the nucleus basalis. Neuropharmacology 29:993–999CrossRefGoogle Scholar
  14. Sahakian BJ, Coull JT (1994) Nicotine and tetrahydroaminoacri-dine: evidence for improved attention in patients with dementia of the Alzheimer type. Drug Dev Res 31:80–88CrossRefGoogle Scholar
  15. Soininen H, Partanen J, Laulumaa V, Riekkinen P Sr (1991) Serial EEG in Alzheimer’s disease: 3 year follow-up and clinical outcome. Electroencephalogr Clin Neurophysiol 79:342–348PubMedCrossRefGoogle Scholar
  16. Soininen H, Reinikainen K, Partanen J, Helkala E-L, Paljärvi L, Riekkinen P Sr (1992) Slowing of electroencephalogram and choline acetyltransferase activity in post mortem frontal cortex in definite Alzheimer’s disease. Neuroscience 49:529–535PubMedCrossRefGoogle Scholar
  17. Soininen H, Kosunen O, Helisalmi S, Mannermaa A, Paljärvi L, Talasniemi S, Ryynänen M, Riekkinen P Sr (1995a) A severe loss of choline acetyltransferase in the frontal cortex of Alzheimer patients carrying apolipoprotein E4 allele. Neurosci Lett 187:79–82PubMedCrossRefGoogle Scholar
  18. Soininen H, Partanen K, Pitkänen A, Hallikainen M, Hänninen T, Helisalmi S, Mannermaa A, Ryynänen M, Koivisto K, Riekkinen P Sr (1995b) Decreased hippocampal volume asymmetry on MRIs in nondemented elderly subjects carrying the apolipoprotein E4 allele. Neurology 45:391PubMedGoogle Scholar
  19. Whitehouse P, Price DL, Struble RG, Clark AW, Coyle JT, DeLong RM (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Paavo Riekkinen
    • 1
  • Hilkka Soininen
    • 1
  • Juhani Partanen
    • 2
  • Ari Pääkkönen
    • 2
  • Seppo Helisalmi
    • 3
  • Paavo Riekkinen
    • 4
  1. 1.Department of NeurologyUniversity Hospital of KuopioKuopioFinland
  2. 2.Department of Clinical NeurophysiologyUniversity Hospital of KuopioKuopioFinland
  3. 3.Unit of Clinical Genetics of the Department of Gynecology and ObstetricsUniversity Hospital of KuopioKuopioFinland
  4. 4.A.I.Virtanen Institute, Department of NeuroscienceUniversity of KuopioKuopioFinland

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