Monoaminergic activities in Lewy Body dementia: Relation to hallucinosis and extrapyramidal features

  • E. K. Perry
  • E. Marshall
  • P. Thompson
  • I. G. McKeith
  • D. Collerton
  • A. F. Fairbairn
  • I. N. Ferrier
  • D. Irving
  • R. H. Perry
Full Papers
  • 46 Downloads

Summary

Serotonergic (5-HT) and dopaminergic activities have been examined in Lewy Body Dementia (LBD) and compared with Parkinson's disease (PD) and Alzheimer's disease (AD). In the neocortex the LBD subgroup experiencing hallucinations was distinguised from the other categories by an increase in the 5HIAA:5HT ratio measured in frontal cortex and by the serotonergic (5-HIAA or 5-HIAA:5-HT): cholinergic (choline acetyltransferase) ratio in frontal and temporal cortex. In the neostriatum (caudate nucleus), loss of dopamine and increased HVA: dopamine ratio correlated with the reduction in substantia nigra neurons in LBD but not PD, despite the greater loss of neurones and dopamine and the higher dopamine turnover ratio in PD. LBD patients experiencing severe Parkinsonism as a result of neuroleptic treatment tended to have lower neuron counts, in combination with higher turnover ratios, than the remainder. Qualitative differences between LBD and PD included decreased cortical 5-HT turnover in PD compared with the increase in LBD. There were no significant changes in any parameter in AD, with the exception of a reduction in temporal cortex 5HIAA. The results suggest that although the neurochemical pathology of LBD and PD involves similar systems, the nature of the derangements differs sufficiently between the diseases to account for differences in symptomatology.

Keywords

Dopamine HVA 5-HT 5-HIAA choline acetyltransferase Parkinson's disease Alzheimer's disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Burns A, Luthert P, Levy R, Jacoby R, Lantos P (1990) Accuracy of clinical diagnosis of Alzheimer's disease. Br Med J 301: 1026Google Scholar
  2. Byrne EJ (1992) Diffuse Lewy body disease: disease, spectrum disorder or variety of Alzheimer's disease. Int J Geriatr Psychiatry 7: 229–234CrossRefGoogle Scholar
  3. Byrne EJ, Lennox G, Godwin-Austen RB (1991) Dementia associated with cortical Lewy bodies: proposed clinical diagnostic criteria. Dementia 2: 283–284Google Scholar
  4. Chan-Palay V, Hüchli M, Jentsch B, Leonard B, Zetzsche T (1992) Raphé serotonin neurons in the human brain stem in normal controls and patients with senile dementia of the Alzheimer type and Parkinson's disease: relationship to monoamine oxidase enzyme localization. Dementia 3: 253–269Google Scholar
  5. Cheng AVT, Ferrier IN, Morris CM, Jabeen S, Sahgal A, McKeith IG, Edwardson JA, Perry, RH, Perry EK (1991) Cortical serotonin-S2 receptor binding in lewy body dementia, Alzheimer's and Parkinson's diseases. J Neurol Sci 106: 50–55CrossRefPubMedGoogle Scholar
  6. Cross AJ, Crow TY, Johnson JA, Joseph MH, Perry EK, Perry RH, Blessed G, Tomlinson BE (1983) Monoamine metabolism in senile dementia of Alzheimertype. J Neurol Sci 60: 383–392CrossRefPubMedGoogle Scholar
  7. Curcio CA, Kemper T (1984) Nucleus raphé dorsalis in dementia of the Alzheimer type: neurofibrillary changes and neuronal packing density. J Neuropathol Exp Neurol 43: 359–368PubMedGoogle Scholar
  8. Dickson DW, Davies P, Mayeux R (1987) Diffuse Lewy body disease: neuropathological and biochemical studies in 6 patients. Acta Neuropathol 75: 8–15CrossRefPubMedGoogle Scholar
  9. Gibb WRG, Esiri MM, Lees AJ (1987) Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain 110: 1131–1153PubMedGoogle Scholar
  10. Hansen L, Salmon D, Galasko D (1990) The Lewy body variant of Alzheimer's disease: a clinical and pathological entity. Neurology 40: 1–8Google Scholar
  11. Hornykiewicz O (1993) Parkinson's disease and the adaptive capacity of the nigrostriatal dopamine systems. Adv Neurol 60: 140–147PubMedGoogle Scholar
  12. Jellinger K (1986) Overview of morphological changes in Parkinson's disease. Adv Neurol 45: 1–18Google Scholar
  13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275PubMedGoogle Scholar
  14. McKeith IG, Perry RH, Fairbairn AF, Jabeen S, Perry EK (1992a) Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med 22: 911–922PubMedGoogle Scholar
  15. McKeith IG, Perry RH, Fairbairn AF, Perry EK (1992b) Neuroleptic sensitivity in patients with senile dementia of Lewy body type. Br Med J 305: 673–678Google Scholar
  16. Marshall EF, Dodds S, Alderson E, Leech M (1990) Biochemical and behavioural study of tryptophan administration to mice treated neonatally with 5,7-'dihydroxytryptamine. In: Lubec G, Rosenthal GA (eds) Amino acids — chemistry, biology and medicine. Escom, Leiden, pp 391–397Google Scholar
  17. Nazarali AJ, Reynolds GP (1992) Monoamine neurotransmitters and their metabolities in brain regions in Alzheimer's disease: a postmortem study. Cell Mol Neurobiol 12: 581–587CrossRefPubMedGoogle Scholar
  18. Perry EK, Curtis M, Dick DJ, Candy JM, Atack JR, Bloxham CA, Blessed G, Fairbairn AF, Tomlinson BE, Perry RH (1985) Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease. J Neurol Neurosurg Psychiatry 48: 413–421PubMedGoogle Scholar
  19. Perry RH, Irving D, Blessed G, Perry EK, Fairbairn AF (1989) Clinically and neuropathologically distinct form of dementia in the elderly. Lancet i: 166CrossRefGoogle Scholar
  20. Perry EK, Marshall E, Perry RH, Irving D, Smith CJ, Blessed G, Fairbairn AF (1990a) Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alz Dis Assoc Disord 42: 87–95Google Scholar
  21. Perry EK, Marshall E, Kerwin JM, Smith CJ, Jabeen S, Cheng AV, Perry RH (1990b) Evidence of a monoaminergic: cholinergic imbalance related to visual hallucinations in Lewy body dementia. J Neurochem 55 4: 1454–1456PubMedGoogle Scholar
  22. Perry EK, Kerwin JM, Perry RH, Irving D, Blessed G, Fairbairn AF (1990c) Cerebral cholinergic activity is related to the incidence of visual hallucinations in senile dementia of Lewy body type. Dementia 1: 2–4Google Scholar
  23. Perry RH, Irving D, Blessed G, Fairbairn AF, Perry EK (1990d) Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 95: 119–139CrossRefPubMedGoogle Scholar
  24. Perry RH, Irving D, Blessed G, Perry EK, Smith CJ, Fairbairn, AF (1990e) Dementia in old age: identification of a clinically and pathologically distinct disease category. Adv Neurol 51: 41–46PubMedGoogle Scholar
  25. Smith PEM, Irving D, Perry RH (1991) Density, distribution and prevalance of Lewy bodies in the elderly. Neurosci Res Commun 8: 127–135Google Scholar
  26. Yamamoto T, Hirano A (1985) Nucleus raphe dorsalis in Alzheimer's disease: neurofibrillary tangles and loss of large neurons. Ann Neurol 17: 573–577CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • E. K. Perry
    • 1
  • E. Marshall
    • 2
  • P. Thompson
    • 3
  • I. G. McKeith
    • 4
  • D. Collerton
    • 3
  • A. F. Fairbairn
    • 4
  • I. N. Ferrier
    • 1
  • D. Irving
    • 5
  • R. H. Perry
    • 5
  1. 1.MRC Neurochemical Pathology UnitNewcastle General HospitalNewcastle upon TyneUK
  2. 2.Department of PsychiatryUniversity of Newcastle upon TyneNewcastle upon Tyne
  3. 3.Bensham General HospitalGateshead
  4. 4.Brighton ClinicNewcastle General HospitalNewcastle upon TyneUK
  5. 5.Department of NeuropathologyNewcastle General HospitalNewcastle upon TyneUK

Personalised recommendations