Skip to main content
SpringerLink
Log in

The role of acetylcholine and dopamine in dementia and psychosis in Parkinson’s disease

  • Conference paper
Advances in Research on Neurodegeneration

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 65))

Summary

Parkinson’s disease (PD) is a progressive neurological disorder in which there is abnormal degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area combined with a varying degree of deterioration of the cholinergic, serotonergic and noradrenergic system, leading to a variety of motor and non-motor abnormalities. Dopamine (DA) depletion in nigrostriatal projections manifests with abnormal spontaneous motor behavior and (subtle) cognitive deficits, whereas more overt cognitive impairment may develop with concomitant DA-deficiency related mesocor-ticolimbic denervation. In combination with a progressive dysfunction of the ascending neocortical cholinergic (and serotonergic and noradrenergic) projections, mainly due to a loss of cholinergic neurons in the nucleus basalis of Meynert (NbM), these cognitive deficits may proceed into dementia sometimes in combination with psychotic behavior, which might also be associated with dopaminomimetic and/or anticholinergic treatment as well as with cholinergic deficit or dopaminomimetic induced REM sleep disturbances.

As these psychiatric symptoms have a substantial negative effect on the patient’s quality of life, contribute to caregiver distress and are predictive of nursing home placement, identification and adequate treatment is of great importance. Recent evidence supports a possible role for cholinomimetic therapy in alleviating cognitive dysfunction and psychotic symptoms in PD.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

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

  • Aarsland D, Larsen JP, Cummins JL, Laake K (1999a) Prevalence and clinical correlates of psychotic symptoms in Parkinson disease: a community-based study. Arch Neurol 56: 595–601

    Article  PubMed  CAS  Google Scholar 

  • Aarsland D, Larsen JP, Karlsen K, Lim NG, Tandberg E (1999b) Mental symptoms in Parkinson’s disease are important contributors to caregiver distress. Int J Geriatr Psychiatry 14: 866–874

    Article  PubMed  CAS  Google Scholar 

  • Aarsland D, Larsen JP, Tandberg E, Laake K (2000) Predictors of nursing home placement in Parkinson’s disease: a population-based, prospective study. J Am Geriatr Soc 48: 938–942

    PubMed  CAS  Google Scholar 

  • Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P (2001a) Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology 56: 730–736

    Article  PubMed  CAS  Google Scholar 

  • Aarsland D, Ballard C, Larsen JP, McKeith I (2001b) A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson’s disease with and without dementia. Int J Geriatr Psychiatry 16: 528–536

    Article  PubMed  CAS  Google Scholar 

  • Arnulf I, Bonnet AM, Damier P, Bejjani BP, Seilhean D, Derenne JP, Agid Y (2000) Hallucinations, REM sleep, and Parkinson’s disease: a medical hypothesis. Neurology 55: 281–288

    Article  PubMed  CAS  Google Scholar 

  • Cornelia CL, Tanner CM, Ristanovic RK (1993) Polysomnographic sleep measures in Parkinson’s disease patients with treatment-induced hallucinations. Ann Neurol 34: 710–714

    Article  Google Scholar 

  • Cools AR, Berger HJ, Buytenhuis EL, Horstink MW, van Spaendonck KP (1994) Manifestations of switching disorders in animal and man with dopamine deficits in A10 and/or A9 circuitries. In: Wolters ECh, Scheltens Ph (eds) Mental dysfunction in Parkinson’s disease. ICG Publications, Dordrecht, pp 49–67

    Google Scholar 

  • Cools AR, Swainson R, Owen AM, Robbins TW (1999) Cognitive dysfunction in non-demented Parkinson’s disease. In: Wolters ECh, Scheltens Ph, Berendse HW (eds) Mental dysfunction in Parkinson’s disease II. APP, Utrecht, pp 142–164

    Google Scholar 

  • Cummings JL (1993) Frontal-subcortical circuits and human behavior. Arch Neurol 50: 873–880

    Article  PubMed  CAS  Google Scholar 

  • de Smet Y, Ruberg M, Serdaru M, Dubois B, Lhermitte F, Agid Y (1982) Confusion, dementia and anticholinergics in Parkinson’s disease. J Neurol Neurosurg Psychiatry 45: 1161–1164

    Article  PubMed  Google Scholar 

  • Dubois B, Pillon B (1999) Dementia in Parkinson’s disease. In: Wolters ECh, Scheltens Ph, Berendse HW (eds) Mental dysfunctions in Parkinson’s disease II. APP, Utrecht, pp 165–176

    Google Scholar 

  • Dubois B, Hauw JJ, Ruberg M, Serdaru M, Javoy-Agid F, Agid Y (1985) Dementia and Parkinson’s disease: biochemical and anatomo-clinical correlation. Rev Neurol (Paris) 141: 184–193

    CAS  Google Scholar 

  • Dubois B, Pillon B, Sternic N, Lhermitte F, Agid Y (1990) Age-induced cognitive disturbances in Parkinson’s disease. Neurology 40: 38–41

    Article  PubMed  CAS  Google Scholar 

  • Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48: 649–684

    Article  PubMed  CAS  Google Scholar 

  • Fergusson E, Howard R (2000) Donepezil for the treatment of psychosis in dementia with Lewy bodies. Int J Geriatr Psychiatry 15: 280–281

    Article  PubMed  CAS  Google Scholar 

  • Goetz CG, Stebbins GT (1993) Risk factors for nursing home placement in advanced Parkinson’s disease. Neurology 43: 2227–2229

    Article  PubMed  CAS  Google Scholar 

  • Goetz CG, Vogel C, Tanner CM, Stebbins GT (1998) Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology 51: 811–814

    Article  PubMed  CAS  Google Scholar 

  • Grace J, Daniel S, Stevens T, Shankar KK, Walker Z, Byrne EJ, Butler S, Wilkinson D, Woolford J, Waite J, McKeith IG (2001) Long-term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial. Int Psychogeriatr 13: 199–205

    Article  PubMed  CAS  Google Scholar 

  • Graybiel AM (1997) The basal ganglia and cognitive pattern generators. Schizophr Bull 23: 459–469

    Article  PubMed  CAS  Google Scholar 

  • Harding AJ, Lakay B, Halliday GM (2002) Selective hippocampal neuron loss in dementia with Lewy bodies. Ann Neurol 51: 125–128

    Article  PubMed  Google Scholar 

  • Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84: 5976–5980

    Article  PubMed  CAS  Google Scholar 

  • Huber SJ, Shuttleworth EC, Freidenberg DL (1989) Neuropsychological differences between the dementias of Alzheimer’s and Parkinson’s diseases. Arch Neurol 46: 1287–1291

    Article  PubMed  CAS  Google Scholar 

  • Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM, Clark CM, Glosser G, Stern MB, Gollomp SM, Arnold SE (2000) Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 54: 1916–1921

    Article  PubMed  CAS  Google Scholar 

  • Hutchinson M, Fazzini E (1996) Cholinesterase inhibition in Parkinson’s disease. J Neurol Neurosurg Psychiatry 61: 324–325

    Article  PubMed  CAS  Google Scholar 

  • Jellinger K (1988) The pedunculopontine nucleus in Parkinson’s disease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 51: 540–543

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (1999) Neuropathological correlates of mental dysfunction in Parkinson’s disease: an update. In: Wolters ECh, Scheltens Ph, Berendse HW (eds) Mental dysfunctions in Parkinson’s disease II. APP, Utrecht, pp 82–105

    Google Scholar 

  • Jenner P, Olanow CW (1998) Understanding cell death in Parkinson’s disease. Ann Neurol 44: S72–S84

    PubMed  CAS  Google Scholar 

  • Karlsen KH, Larsen JP, Tandberg E, Maland JG (1998) Quality of life measurements in patients with Parkinson’s disease: a community-based study. Eur J Neurol 5: 443–450

    Article  PubMed  Google Scholar 

  • Klatka LA, Louis ED, Schiffer RB (1996) Psychiatric features in diffuse Lewy body disease: a clinicopathologic study using Alzheimer’s disease and Parkinson’s disease comparison groups. Neurology 47: 1148–1152

    Article  PubMed  CAS  Google Scholar 

  • Klein C, Kompf D, Pulkowski U, Moser A, Vieregge P (1997) A study of visual hallucinations in patients with Parkinson’s disease. J Neurol 244: 371–377

    Article  PubMed  CAS  Google Scholar 

  • Kuhl DE, Minoshima S, Fessler JA, Frey KA, Foster NL, Ficaro EP, Wieland DM, Koeppe RA (1996) In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 40: 399–410

    Article  PubMed  CAS  Google Scholar 

  • Mattay VS, Tessitore A, Callicott JH, Bertolino A, Goldberg TE, Chase TN, Hyde TM, Weinberger DR (2002) Dopaminergic modulation of cortical function in patients with Parkinson’s disease. Ann Neurol 51: 156–164

    Article  PubMed  CAS  Google Scholar 

  • Mattila PM, Roytta M, Torikka H, Dickson DW, Rinne JO (1998) Cortical Lewy bodies and Alzheimer-type changes in patients with Parkinson’s disease. Acta Neuropathol (Berl) 95: 576–582

    Article  CAS  Google Scholar 

  • Mattila PM, Roytta M, Lonnberg P, Marjamaki P, Helenius H, Rinne JO (2001) Choline acetytransferase activity and striatal dopamine receptors in Parkinson’s disease in relation to cognitive impairment. Acta Neuropathol (Berl) 102: 160–166

    CAS  Google Scholar 

  • Mayeux R, Stern Y, Rosenstein R, Marder K, Hauser A, Cote L, Fahn S (1988) An estimate of the prevalence of dementia in idiopathic Parkinson’s disease. Arch Neurol 45: 260–262

    Article  PubMed  CAS  Google Scholar 

  • McKeith I, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin-Sain A, Ferrara R, Spiegel R (2000a) Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 356: 2031–2036

    Article  PubMed  CAS  Google Scholar 

  • McKeith IG, Grace JB, Walker Z, Byrne EJ, Wilkinson D, Stevens T, Perry EK (2000b) Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. Int J Geriatr Psychiatry 15: 387–392

    Article  PubMed  CAS  Google Scholar 

  • Mesulam MM, Geula C, Bothwell MA, Hersh LB (1989) Human reticular formation: cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons. J Comp Neurol 283: 611–633

    Article  PubMed  CAS  Google Scholar 

  • Mesulam MM, Mufson EJ, Wainer BH, Levey AI (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Chl-Ch6). Neuroscience 10: 1185–1201

    Article  PubMed  CAS  Google Scholar 

  • Pappert EJ, Goetz CG, Niederman FG, Raman R, Leurgans S (1999) Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson’s disease. Mov Disord 14: 117–121

    Article  PubMed  CAS  Google Scholar 

  • Paulus W, Jellinger K (1991) The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol 50: 743–755

    Article  PubMed  CAS  Google Scholar 

  • Perry EK, Curtis M, Dick DJ, Candy JM, Atack JR, Bloxham CA, Blessed G, Fairbairn A, Tomlinson BE, Perry RH (1985) Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 48: 413–421

    Article  PubMed  CAS  Google Scholar 

  • Pillon B, Dubois B, Ploska A, Agid Y (1991) Severity and specificity of cognitive impairment in Alzheimer’s, Huntington’s, and Parkinson’s diseases and progressive supranuclear palsy. Neurology 41: 634–643

    Article  PubMed  CAS  Google Scholar 

  • Pillon B, Deweer B, Agid Y, Dubois B (1993) Explicit memory in Alzheimer’s, Huntington’s, and Parkinson’s diseases. Arch Neurol 50: 374–379

    Article  PubMed  CAS  Google Scholar 

  • Reading PJ, Luce AK, McKeith IG (2001) Rivastigmine in the treatment of parkinsonian psychosis and cognitive impairment: preliminary findings from an open trial. Mov Disord 16: 1171–1174

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Ramos JR, Ortoll R, Paulson GW (1996) Visual hallucinations associated with Parkinson disease. Arch Neurol 53: 1265–1268

    Article  PubMed  CAS  Google Scholar 

  • Sarter M, Bruno JP (1997) Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Brain Res Rev 23: 28–46

    Article  PubMed  CAS  Google Scholar 

  • Sarter M, Bruno JP (1999) Abnormal regulation of corticopetal cholinergic neurons and impaired information processing in neuropsychiatric disorders. Trends Neurosci 22: 67–74

    Article  PubMed  CAS  Google Scholar 

  • Scheltens Ph (1999) Dementia in Parkinon’s disease: subclinical Alzheimer’s disease? In: Wolters ECh, Scheltens Ph, Berendse HW (eds) Mental dysfunctions in Parkinson’s disease II. APP, Utrecht, pp 189–193

    Google Scholar 

  • Shea C, MacKnight C, Rockwood K (1998) Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Int Psychogeriatr 10: 229–238

    Article  PubMed  CAS  Google Scholar 

  • Shinotoh H, Namba H, Yamaguchi M, Fukushi K, Nagatsuka S, Iyo M, Asahina M, Hattori T, Tanada S, Irie T (1999) Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson’s disease and progressive supranuclear palsy. Ann Neurol 46: 62–69

    Article  PubMed  CAS  Google Scholar 

  • Svensson TH, Mathe JM, Andersson JL, Nomikos GG, Hildebrand BE, Marcus M (1995) Mode of action of atypical neuroleptics in relation to the phencyclidine model of schizophrenia: role of 5-HT2 receptor and alpha 1-adrenoceptor antagonism [corrected]. J Clin Psychopharmacol 15: 11S–18S

    Article  PubMed  CAS  Google Scholar 

  • Tiraboschi P, Hansen LA, Alford M, Sabbagh MN, Schoos B, Masliah E, Thal LJ, Corey-Bloom J (2000) Cholinergic dysfunction in diseases with Lewy bodies. Neurology 54: 407–411

    Article  PubMed  CAS  Google Scholar 

  • Werber EA, Rabey JM (2001) The beneficial effect of Cholinesterase inhibitors on patients suffering from Parkinson’s disease and dementia. J Neural Transm 108: 1319–1325

    Article  PubMed  CAS  Google Scholar 

  • Wesnes KA, McKeith IG, Ferrara R, Emre M, Del Ser T, Spano PF, Cicin-Sain A, Anand R, Spiegel R (2002) Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system. Dement Geriatr Cogn Disord 13: 183–192

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse PJ, Hedreen JC, White CL, III, Price DL (1983) Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol 13: 243–248

    Article  PubMed  CAS  Google Scholar 

  • Wolters EC (2001a) Intrinsic and extrinsic psychosis in Parkinson’s disease. J Neurol 248[Suppl 3]: III22–III27

    PubMed  Google Scholar 

  • Wolters EC (2001b) Psychiatric complications in the treatment of Parkinson’s disease. Adv Neurol 86: 385–393

    PubMed  CAS  Google Scholar 

  • Wolters EC, Berendse HW (2001c) Management of psychosis in Parkinson’s disease. Curr Opin Neurol 14: 499–504

    Article  PubMed  CAS  Google Scholar 

  • Wolters EC, Francot CMJE (1998) Mental dysfunctions in Parkinson’s disease. Parkinsonism and Related Disorders 4: 107–112

    Article  PubMed  CAS  Google Scholar 

  • Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26: 41–46

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institute Neurosciences Vrije Universiteit, Department of Neurology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands

    J. L. W. Bosboom, D. Stoffers & Prof. Dr. E. Ch. Wolters

  2. Department of Neurology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Prof. Dr. E. Ch. Wolters

Authors
  1. J. L. W. Bosboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Stoffers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prof. Dr. E. Ch. Wolters
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Neurobiotec, Berlin, Federal Republic of Germany

    R. Horowski

  2. Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

    Y. Mizuno

  3. Department of Neurology, The Mount Sinai Medical Center, New York, NY, USA

    C. W. Olanow

  4. Department of Neurology, University of Innsbruck, Innsbruck, Austria

    W. H. Poewe

  5. Department of Psychiatry, University of Würzburg, Würzburg, Federal Republic of Germany

    P. Riederer

  6. Neurodegenerative Disorders Centre, The University of British Columbia, Vancouver, B.C., Canada

    J. A. Stoessl

  7. Department of Pharmacology, Technion — Israel Institute of Technology, Haifa, Israel

    M. B. H. Youdim

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Wien

About this paper

Cite this paper

Bosboom, J.L.W., Stoffers, D., Wolters, E.C. (2003). The role of acetylcholine and dopamine in dementia and psychosis in Parkinson’s disease. In: Horowski, R., et al. Advances in Research on Neurodegeneration. Journal of Neural Transmission. Supplementa, vol 65. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0643-3_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0643-3_11

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83907-2

  • Online ISBN: 978-3-7091-0643-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation