Skip to main content
SpringerLink
Log in

Cholinergic Component of Cognitive Impairment in Dementia

  • Chapter
Dementia

Abstract

The principal thesis of this chapter — that, irrespective of aetiology, cholinergic dysfunction in key areas of the brain especially in temporal lobe is associated with cognitive impairment — is not novel. A convincing body of evidence that abnormalities of the basal forebrain system are related to memory loss and other symptoms of dementia, such as hallucinations, has been derived from neurochemical, neuropathological, pharmacological and behavioural sources spanning nearly two decades of research. So much has been written (for recent reviews, see for example Perry, 1986, 1988; Chozick, 1987; Cummings and Benson, 1987) that the merit of yet another chapter on the subject might well be questioned. However, the current development and application of cholinergic treatment strategies in dementia, together with new advances in the understanding of relevant trophic factors, more than justify a further critical appraisal of the subject.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agid, Y., Ruberg, M., Raisman, R. et al. (1990) The biochemistry of Parkinson’s disease. In Parkinson’s Disease (ed. G.M. Stern ), Chapman and Hall Medical, London, pp. 99–126.

    Google Scholar 

  • Allen, S.J., Dawbarn, D., MacGowan, S.H. et al. (1990) Quantitative morphometric analysis of basal forebrain neurons expressing 13-nerve growth factor receptors in normal and Alzheimer’s disease brains. Dementia, 1, 125–37.

    Google Scholar 

  • Barnes, J.M., Costall, B., Coughlan, J. et al. (1990) The effects of Ondansetron, a 5HT3 receptor antagonist, on cognition in rodents and primates. Pharmacol. Biochem. Behay., 35, 955–62.

    Article  CAS  Google Scholar 

  • Baron, J.A. (1986) Cigarette smoking and Parkinson’s disease. Neurology, 36, 1490–6.

    Article  PubMed  CAS  Google Scholar 

  • Beal, M.F., Clevens, R.A., Chatta, G.K. et al. (1988) Galanin-like immunoreactivity is unchanged in Alzheimer’s disease and Parkinson’s disease dementia cerebral cortex. J. Neurochem., 21, 1935–41.

    Article  Google Scholar 

  • Bowen, D.M. (1983) Biochemical assessment of neurotransmitter and metabolic dysfunction and cerebral atrophy in Alzheimer’s disease. In Biological Aspects of Alzheimer’s Disease (ed. R. Katzman ), Cold Spring Harbor Laboratory, Cold Spring Harbor, pp. 219–32.

    Google Scholar 

  • Burton, K. and Calne, D.B. (1990) Aetiology of Parkinson’s disease. In Parkinson’s Disease (ed. G.M. Stern ), Chapman and Hall Medical, London, pp. 269–94.

    Google Scholar 

  • Buzsaki, G. and Gage, F.H. (1989) The cholinergic nucleus basalis: a key structure in neocortical arousal. In Central Cholinergic Synaptic Transmission (eds M. Frotscher and U. Misgeld ), Birk-hausen Verlag, Basel, pp. 159–71.

    Chapter  Google Scholar 

  • Byrne, E.J., Lennox, G., Lowe, J. and Godwin-Austen, R.B. (1989) Diffuse Lewy body disease. Clinical features in 15 cases. J. Neurol. Neurosurg. Psychiatry, 52, 709–18.

    Article  PubMed  CAS  Google Scholar 

  • Chozick, B. (1987) The nucleus basalis of Meynert in neurological dementing disease: a review. Int. J. Neurosci., 37, 31–48.

    Article  PubMed  CAS  Google Scholar 

  • Court, J.A. and Perry, E.K. (1992) Dementia: the neurochemical basis of putative transmitter orientated therapy. J. Pharmacol. Exp. Ther. (in press).

    Google Scholar 

  • Cummings, J.L. and Benson, D.F. (1987) The role of the nucleus basalis of Meynert in dementia: review and reconsideration. Alzheimer Dis. Assoc. Disord., 1, 128–45.

    Article  PubMed  CAS  Google Scholar 

  • Decker, M.W. and McGaugh, J.L. (1991) The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse, 7, 151–68.

    Article  PubMed  CAS  Google Scholar 

  • Deneris, E.S., Connolly, J., Rogers, S.W. and Duvoisin, R. (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors. Trends Pharmacol. Sci., 12, 34–40.

    Article  PubMed  CAS  Google Scholar 

  • Dubois, B., Pillon, B., Lhermitte, F. and Agid, Y. (1990) Cholinergic deficiency and frontal dysfunction in Parkinson’s disease. Ann. Neurol., 28, 117–21.

    Article  PubMed  CAS  Google Scholar 

  • Dunnett, S. (1991) Cholinergic grafts, memory and ageing. Trends Neurosci., 14, 371–6.

    Article  PubMed  CAS  Google Scholar 

  • Eagger, S.A., Levy, R. and Sahakian, B.J. (1991) Tacrine in Alzheimer’s disease. Lancet, 337, 989–92.

    Article  PubMed  CAS  Google Scholar 

  • Ebendal, T., Soderström, S., Kylberg, A. et al. (1991) Biological and immunological properties of nerve growth factor and related proteins: clinical possibilities in dementia. Biol. Psychiatry, 29, 1415–23.

    Google Scholar 

  • Enz, A., Boddeke, H., Gray, J. and Spiegel, R. (1991) Pharmacological and clinical—pharmacological properties of SDZ ENA 713, a centrally selective acetylcholinesterase inhibitor. Proc. Natl Acad. Sci. USA (in press).

    Google Scholar 

  • Ernfors, P., Lindefors, N., Chan-Palay, V. and Persson, H. (1990) Cholinergic neurons in the nucleus basalis express elevated levels of nerve growth factor receptor mRNA in senile dementia of the Alzheimer type. Dementia, 1, 138–45.

    Google Scholar 

  • Everitt, B.J., Sirkia, T.E., Roberts, A.C. et al. (1988) Distribution and some projections of cholinergic neurons in the brain of the common marmoset, callithrix jacchus. J. Comp. Neurol., 271, 533–58.

    Article  PubMed  CAS  Google Scholar 

  • Fewster, P.A., Griffin-Brooks, S., MacGregor, J. et al. (1991) A topographical pathway by which histopathological lesions disseminate through the brain of patients with Alzheimer’s disease. Dementia, 2, 121–31.

    Google Scholar 

  • Fibiger, H.C. (1991) Cholinergic mechanisms of learning, memory and dementia: a review of the evidence. Trends Neurosci., 14, 220–4.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, W., Bjorklund, A. and Chen, K. (1991) Nerve growth factor improving spatial memory in aged rodents as a function of age. J. Neurosci., 11, 1889–906.

    PubMed  CAS  Google Scholar 

  • Giacobini, E., De Sarno, P., Clark, B. and Mcllhany, M. (1989) The cholinergic receptor system of the human brain: neurochemical and phar macological aspects in aging and Alzheimer’s. Prog. Brain Res., 79, 335–44.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, M., Fine, A., Hunt, S.P. and Ullrich, U. (1986) Nerve growth factor mRNA in peripheral and central rat tissues and in the human central nervous system: lesion effects in the rat brain and levels in Alzheimer’s disease. Mol. Brain Res., 1, 85–92.

    Article  Google Scholar 

  • Goedert, M., Fine, A., Dawbarn, D. et al. (1989) Nerve growth factor receptor mRNA distribution in human brain — normal levels in basal forebrain in Alzheimer’s disease. Mol. Brain Res., 5, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Goodman, L.S. and Gilman, A. (1975) The Pharmacological Basis of Therapeutics, Macmillan Publishing Company, New York, pp. 527–31.

    Google Scholar 

  • Harris, D.A., Falls, D.L., Johnson, F.A. and Fischbach, G.D. (1991) A prion like protein from chick brain co-purifies with an acetylcholine receptor inducing activity. Proc. Natl Acad. Sci. USA, 88, 7664–8.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, P.J., Barton, A.J.L., Najlerahim, A. et al. (1991) Increased muscarinic receptor messenger RNA in Alzheimer’s disease temporal cortex demonstrated by in situ hybridization histochemistry. Mol. Brain Res., 9, 15–21.

    Article  PubMed  CAS  Google Scholar 

  • Hefti, F. and Mash, D.C. (1989) Localization of nerve growth factor receptors in the normal human brain and in Alzheimer’s disease. Neurobiol. Aging, 10, 75–87.

    Article  PubMed  CAS  Google Scholar 

  • Hempstead, B.L., Martin-Zanca, D., Kaplan, D.R. et al. (1991) High affinity NGF receptor binding requires co-expression of the trk protooncogene and the low affinity NGF receptor. Nature, 350, 678–83.

    Article  PubMed  CAS  Google Scholar 

  • Janson, A.M., Agnati, L.F., Jansson, A. et al. (1989) Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat. Prog. Brain Res., 79, 257–65.

    Article  PubMed  CAS  Google Scholar 

  • Kellar, K.J. and Wonnacott, S. (1990) Nicotinic cholinergic receptors in Alzheimer’s Disease. In Nicotine Psychopharmacology: Molecular, Cellular and Behavioural Aspects (eds S. Wonnacott, M.A.H. Russell and I.P. Stolerman ), Oxford University Press, pp. 341–73.

    Google Scholar 

  • Kerwin, J.M., Morris, C.M., Perry, R.H. and Perry, E.K. (1991) Distribution of nerve growth factor receptor immunoreactivity in the human hippo-campus. Neurosci. Lett., 121, 178–82.

    Article  PubMed  CAS  Google Scholar 

  • Kish, S.J., Currier, R.D., Schut, L. et al. (1987) Brain choline acetyltransferase reductions in dominantly inherited olivopontine cerebellar atrophy. Ann. Neurol., 22, 272–4.

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos, V.E., Martin, L.J., Walker, L.C. et al. (1988) Topographic, non-collaterialized basal forebrain projections to amygdala, hippo-campus and anterior cingulate cortex in the rhesus monkey. Brain Res., 463, 133–9.

    Article  PubMed  CAS  Google Scholar 

  • Korsching, S. (1986) The role of nerve growth factor in the CNS. Trends Neurosci., 9, 570–3.

    Article  CAS  Google Scholar 

  • Metherate, R., Temblay, N. and Dyke, R.W. (1987) Acetylcholine permits long term enhancement of neuronal responsiveness in cat primary somatosensory cortex. Neuroscience, 22, 75–81.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E.J., Presley, L.N. and Kordower, J.H. (1991) Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson’s disease: reduced cell numbers and co-localization with cholinergic neurons. Brain Res., 539, 19–30.

    Article  PubMed  CAS  Google Scholar 

  • Nawa, H., Nakanishi, S. and Patterson, P.H. (1991) Recombinant cholinergic differentiation factor (leukemia inhibitory factor) regulates sympathetic neuron phenotype by alterations in the size and amounts of neuropeptide mRNAs. J. Neurochem., 56, 2147–50.

    Article  PubMed  CAS  Google Scholar 

  • Newhouse, P.A., Sunderland, T., Tariot, P.N. et al. (1988) Intravenous nicotine in Alzheimer’s disease: a pilot study. Psychopharmacology, 98, 171–5.

    Google Scholar 

  • Nordberg, A., Adem, A., Nilsson, L. et al. (1988) Heterogenous cholinergic nicotinic receptors in the CNS. In Nicotinic Acetylcholine Receptors in the Nervous System (eds F. Clementi, C. Gotti and E. Sher ), Springer Verlag, Berlin, pp. 331–50.

    Chapter  Google Scholar 

  • Perry, E.K. (1986) The cholinergic hypothesis — ten years on. Br. Med. Bull., 42, 63–9.

    PubMed  CAS  Google Scholar 

  • Perry, E.K. (1988) Alzheimer’s disease and acetylcholine. Br. J. Psychiatry, 152, 737–40.

    Article  PubMed  CAS  Google Scholar 

  • Perry, E.K. (1990a) Nerve growth factor and the basal forebrain cholinergic system: a link in the aetiopathology of neurodegenerative dementias? Alzheimer Dis. Assoc. Disord., 4, 1–13.

    Article  PubMed  CAS  Google Scholar 

  • Perry, E.K. (1990b) Hypothesis linking plasticity, vulnerability and nerve growth factor to basal forebrain cholinergic neurons. Int. J. Geriatr. Psychiatry, 5, 223–31.

    Article  Google Scholar 

  • Perry, E.K., Tomlinson, B.E., Blessed, G. et al. (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br. Med. J., 2, 1457–9.

    Article  PubMed  CAS  Google Scholar 

  • Perry E.K., Curtis, M., Dick, D.J. et al. (1985) Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry, 48, 413–21.

    Article  PubMed  CAS  Google Scholar 

  • Perry, E.K., Smith, C.J., Perry, R.H. et al. (1989a) Regional distribution of muscarinic and nicotinic cholinergic receptor binding activities in the human brain. J. Chem. Neuroanat., 2, 189–99.

    PubMed  CAS  Google Scholar 

  • Perry, E.K., Smith, C.J., Perry, R.H. et al. (1989b) Nicotinic (3H-nicotine) receptor binding in human brain: characterization and involvement in cholinergic neuropathology. Neurosci. Res. Commun., 5, 117–24.

    CAS  Google Scholar 

  • Perry, E.K., Marshall, E., Kerwin, J. et al. (1990a) Evidence of a monoaminergic: cholinergic imbalance related to visual hallucinations in Lewy body dementia. J. Neurochem., 55, 1454–6.

    Article  PubMed  CAS  Google Scholar 

  • Perry, E.K., Smith, C.J., Court, J. A. and Perry, R.H. (1990b) Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types. J. Neural Transm., 2, 149–58.

    Article  CAS  Google Scholar 

  • Perry, E.K., Marshall, E., Perry, R.H. et al. (1990c) Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alzheimer Dis. Assoc. Disord., 4, 87–95.

    PubMed  CAS  Google Scholar 

  • Perry, E.K., Irving, D. and Perry, R.H. (1991) Cholinergic controversies. Trends Neurosci., 14, 482–3.

    Article  Google Scholar 

  • Perry, E.K., Johnson, M., Kerwin, J.M. et al. (1992) Converging archicortical cholinergic activities in aging and Alzheimer’s disease. Neurobiol. Aging (in press).

    Google Scholar 

  • Perry, R.H., Irving, D., Blessed, G. et al. (1990) Senile dementia of Lewy body type: a clinically and histopathologically distinct form of Lewy body dementia in the elderly. J. Neurol. Sci., 95, 119–39.

    Article  PubMed  CAS  Google Scholar 

  • Phillips, H.S., Hains, J.M., Armanini, M. et al. (1991) BDNF on RNA is decreased in the hippo-campus of individuals with Alzheimer’s disease. Neuron, 7, 695–702.

    Article  PubMed  CAS  Google Scholar 

  • Pioro, E.P. and Cuello, A.C. (1990) Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system, effect of colchicine and correlation with the cholinergic system. Neuroscience, 34, 57–82.

    Article  PubMed  CAS  Google Scholar 

  • Ridley, R.M. and Baker, H.F. (1991) Can fetal neural transplants restore function in monkeys with lesion-induced behavioural deficits. Trends Neurosci., 14, 366–70.

    Article  PubMed  CAS  Google Scholar 

  • Ruberg, M., Ploska, A., Javoy-Agid, F. and Agid, Y. (1982) Muscarinic binding and choline acetyltransferase in Parkinsonian subjects with reference to dementia. Brain Res., 232, 129–39.

    Article  PubMed  CAS  Google Scholar 

  • Sahakian, B., Jones, G., Levy, R. et al. (1989) The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of Alzheimer type. Br. J. Psychiatry, 154, 797–800.

    Article  PubMed  CAS  Google Scholar 

  • Sakurada, T., Alufuzoff, F., Winblad, B. and Nordberg, A. (1990) Substance P like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer’s disease and multi infarct dementia. Brain Res., 521, 329–32.

    Article  PubMed  CAS  Google Scholar 

  • Sarter, M., Schneider, H.H. and Stephens, D.N. (1988) Treatment strategies for senile dementia: antagonist ß-carbolines. Trends Neurosci., 11, 13–17.

    Article  PubMed  CAS  Google Scholar 

  • Selby, G. (1990) Clinical features. In Parkinson’s Disease (ed. G.M. Stern ), Chapman and Hall Medical, London, pp. 333–88.

    Google Scholar 

  • Semba, K. and Fibiger, H.C. (1989) Organization of central cholinergic systems. Prog. Brain Res., 79, 37–63.

    Article  PubMed  CAS  Google Scholar 

  • Smith, C.J., Perry, E.K., Fairbairn, A.F. and Birdsall, N.J.M. (1987) Guanine nucleotide modulation of muscarinic cholinergic receptor binding in postmortem human brain — a preliminary study in Alzheimer’s disease. Neurosci. Lett., 82, 227–32.

    Article  PubMed  CAS  Google Scholar 

  • Smith, C.J., Perry, E.K., Perry, R.H. et al. (1988) Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. J. Neurochem., 50, 847–57.

    Article  PubMed  CAS  Google Scholar 

  • Sofroniew, M.V. and Staley, K. (1991) Transgenic modelling of neurodegenerative events gathers momentum. Trends Neurosci., 14, 513–15.

    Article  PubMed  CAS  Google Scholar 

  • Stromberg, I., Wetmore, C.J., Ebendal, T. et al. (1990) Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant nerve growth factor. J. Neurosci. Res., 25, 405–11.

    Article  PubMed  CAS  Google Scholar 

  • Sugihara, H., Andrisani, V. and Salvaterra, P.M. (1991) Genomic organization of Drosophila choline acetyltransferase. J. Neurochem., 57, 1636–42.

    Article  PubMed  CAS  Google Scholar 

  • Thal, L.J., Mandel, R.J., Terry, R.D. et al. (1990) Nucleus basalis lesions fail to induce senile plaques in the rat. Exp. Neurol., 108, 88–90.

    Article  PubMed  CAS  Google Scholar 

  • Thoenen, H. (1991) The changing scene of neuro- trophic factors. Trends Neurosci., 14, 165–70.

    Article  PubMed  CAS  Google Scholar 

  • Treanor, J.J.S., Dawbarn, D., Allen, S.J. et al. (1991) Low affinity nerve growth factor receptor binding in normal and Alzheimer’s disease basal forebrain. Neurosci. Lett., 121, 73–6.

    Article  PubMed  CAS  Google Scholar 

  • Tuszynski, M.H., Sang, H., Yoshida, K. and Gage, F.H. (1991) Recombinant human nerve growth factor infusions prevent cholinergic neuronal degeneration in the adult primate brain. Ann. Neurol., 30, 625–36.

    Article  PubMed  CAS  Google Scholar 

  • Ulrich, J., Meier-Ruge, W., Probst, A. et al. (1990) Senile plaques: staining for acetylcholinesterase and A4 protein: a comparative study in the hippocampus and entorhinal cortex. Acta Neuropathol., 80, 624–8.

    Article  PubMed  CAS  Google Scholar 

  • Van Duijn, C. and Hofman, A. (1991) Relation between nicotine intake and Alzheimer’s disease. Br. Med. J., 302, 1491–4.

    Article  Google Scholar 

  • Wallace, W.C., Bragin, V., Robakis, N.K. et al. (1991) Increased biosynthesis of Alzheimer’s amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert. Mol. Brain Res., 10, 173–8.

    Article  PubMed  CAS  Google Scholar 

  • Watson, G.B., Bolanowski, M.A., Boganoff, M.P. et al. (1990) D-Cyclo-serine acts as a partial agonist at the glycine modulatory site of the NMDA receptor expressed in Xenopus oocytes. Brain Res., 510, 158–60.

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse, P.J., Martino, A.M., Marcus, K.A. et al. (1988) Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch. Neurol., 45, 722–4.

    Article  PubMed  CAS  Google Scholar 

  • Whittemore, S.R. and Seiger, A. (1987) The expression, localization and functional significance of f3-nerve growth factor in the central nervous system. Brain Res. Rev., 12, 439–64.

    Article  CAS  Google Scholar 

  • Wonnacott, S. (1990) The paradox of nicotinic acetylcholine receptor upregulation by nicotine. Trends Pharmacol. Sci., 11, 216–19.

    Article  PubMed  CAS  Google Scholar 

  • Woolf, N.J., Jacobs, R.W. and Butcher, L.L. (1989) The pontomesencephalotegmental cholinergic system does not degenerate in Alzheimer’s disease. Neurosci. Lett., 96, 277–82.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. E. K. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Manchester, UK

    Alistair Burns (Professor of Old Age Psychiatry) (Professor of Old Age Psychiatry)

  2. Institute of Psychiatry, London, UK

    Raymond Levy (Professor of Old Age Psychiatry) (Professor of Old Age Psychiatry)

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Perry, E.K. (1994). Cholinergic Component of Cognitive Impairment in Dementia. In: Burns, A., Levy, R. (eds) Dementia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6805-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-6805-6_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-6807-0

  • Online ISBN: 978-1-4615-6805-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation