Journal of Geriatric Psychiatry and Neurology

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Free Access - Register Here

SAGETRACK

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aarsland, D.
Right arrow Articles by McKeith, I. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aarsland, D.
Right arrow Articles by McKeith, I. G.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Geriatric Psychiatry and Neurology, Vol. 17, No. 3, 164-171 (2004)
DOI: 10.1177/0891988704267463

Role of Cholinesterase Inhibitors in Parkinson’s Disease and dementia with Lewy Bodies

Dag Aarsland, MD, PhD

Rogaland Central Hospital, Psychiatric Clinic, P.O. Box 1163, Hillevaag, 4095 Stavanger, Norwaydaa{at}sir.no

Urs P. Mosimann, MD

Newcastle General Hospital, Wolfson Research Centre, Newcastle, UK

Ian G. McKeith, MD, F Med Sci

Newcastle General Hospital, Institiute for the Elderly, Newcastle, UK

This article reviews the cholinergic changes in Parkinson’s disease and dementia (PDD) and dementia with Lewy bodies (DLB), their potential clinical implications, and the available evidence for cholinesterase inhibitors in the treatment of PDD and DLB. Marked neuronal loss of cholinergic nuclei, reduced cholinergic markers in the neocortex, hippocampus, and selected thalamic nuclei, and receptor changes have been reported. One large and 2 small placebo-controlled trials and nearly 20 open-label studies suggest that cholinesterase inhibitors have a positive effect on cognition, psychiatric symptoms, and global function in patients with DLB and PDD. The treatment is well tolerated in most patients without any apparent worsening of extrapyramidal motor features. Given the high risk of severe sensitivity reactions and increased risk of cerebrovascular incidents during treatment with neuroleptics, more clinical trials of cholinesterase inhibitors are encouraged to establish their precise role in DLB and PDD. (J Geriatr Psychiatry Neurol 2004; 17:164-171)

Key Words: cholinesterase inhibitors • dementia with Lewy bodies • Parkinson’s disease • treatment

References

  • 1. Whitehouse PJ, Hedreen JC, White CL 3rd, Price DL. Basal fore-brain neurons in the dementia of Parkinson disease. Ann Neurol 1983; 13:243-248.[CrossRef][Medline] [Order article via Infotrieve]
  • 2. Lippa CF, Smith TW, Perry E. Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology. J Neural Transm 1999; 106:525-535.
  • 3. Perry EK, Curtis M, Dick DJ, et al. Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1985; 48:413-421.[Abstract]
  • 4. Samuel W, Alford M, Hofstetter CR, Hansen L. Dementia with Lewy bodies versus pure Alzheimer disease: differences in cognition, neuropathology, cholinergic dysfunction, and synapse density. J Neuropathol Exp Neurol 1997; 56:499-508.[Medline] [Order article via Infotrieve]
  • 5. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996; 47:1113-1124.[Abstract/Free Full Text]
  • 6. Perry EK, Irving D, Kerwin JM, et al. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson’s and distinction from Alzheimer disease. Alzheimer Dis Assoc Disord 1993; 7:69-79.[Medline] [Order article via Infotrieve]
  • 7. Aubert I, Araujo DM, Cecyre D, et al. Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer’s and Parkinson’s diseases. J Neurochem 1992; 58:529-541.[Medline] [Order article via Infotrieve]
  • 8. Tiraboschi P, Hansen LA, Alford M, et al. The decline in synapses and cholinergic activity is asynchronous in Alzheimer’s disease. Neurology 2000; 55:1278-1283.[Abstract/Free Full Text]
  • 9. Tiraboschi P, Hansen LA, Alford M, et al. Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease. Arch Gen Psychiatry 2002; 59:946-951.[Abstract/Free Full Text]
  • 10. Kuhl DE, Minoshima S, Fessler JA, et al. In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 1996; 40:399-410.[CrossRef][Medline] [Order article via Infotrieve]
  • 11. Bohnen NI, Kaufer DI, Ivanco LS, et al. Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol 2003; 60:1745-1748.[Abstract/Free Full Text]
  • 12. Jellinger K. The pedunculopontine nucleus in Parkinson’s dis-ease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1988; 51:540-543.[Abstract]
  • 13. Boeve BF, Silber MH, Parisi JE, et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology 2003; 61:40-45.[Abstract/Free Full Text]
  • 14. Ziabreva I, Ballard CL, Aarsland D, et al. Cortical and thalamic cholinergic activity in Lewy body disease in relation to dementia and parkinsonism. Presented at: MDS-Conference, Rome, Italy, 2004.
  • 15. Perry EK, Marshall E, Kerwin J, et al. Evidence of a monoaminergic-cholinergic imbalance related to visual hallucinations in Lewy body dementia. J Neurochem 1990; 55:1454-1456.[CrossRef][Medline] [Order article via Infotrieve]
  • 16. Ballard C, Piggott M, Johnson M, et al. Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Ann Neurol 2000; 48:868-876.[CrossRef][Medline] [Order article via Infotrieve]
  • 17. Court JA, Piggott MA, Lloyd S, et al. Nicotine binding in human striatum: elevation in schizophrenia and reductions in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s dis-ease and in relation to neuroleptic medication. Neuroscience 2000; 98:79-87.[CrossRef][Medline] [Order article via Infotrieve]
  • 18. Burn DJ, Rowan EN, Minett T, et al. Extrapyramidal features in Parkinson’s disease with and without dementia and dementia with Lewy bodies: a cross-sectional comparative study. Mov Disord 2003; 18:884-889.[CrossRef][Medline] [Order article via Infotrieve]
  • 19. Duda JE. Pathology and neurotransmitter abnormalities of dementia with lewy bodies. Dement Geriatr Cogn Disord 2004; 17(suppl 1):3-14.
  • 20. Ballard CG. Advances in the treatment of Alzheimer’s disease: benefits of dual cholinesterase inhibition. Eur Neurol 2002; 47:64-70.[CrossRef][Medline] [Order article via Infotrieve]
  • 21. O’Brien KK, Saxby BK, Ballard CG, et al. Regulation of attention and response to therapy in dementia by butyryl-cholinesterase. Pharmacogenetics 2003; 13:231-239.[CrossRef][Medline] [Order article via Infotrieve]
  • 22. Perry E, McKeith I, Ballard C. Butyrylcholinesterase and progression of cognitive deficits in dementia with Lewy bodies. Neurology 2003; 60:1852-2853.[Abstract/Free Full Text]
  • 23. Sirvio J, Soininen HS, Kutvonen R, et al. Acetyl-and butyryl-cholinesterase activity in the cerebrospinal fluid of patients with Parkinson’s disease. J Neurol Sci 1987; 81:273-279.[Medline] [Order article via Infotrieve]
  • 24. Weinstock M. Selectivity of cholinesterase inhibition. CNS Drugs 1999; 12:307-323.[CrossRef]
  • 25. Reid RT, Sabbagh MN, Corey-Bloom J, et al. Nicotinic receptor losses in dementia with Lewy bodies: comparisons with Alzheimer’s disease. Neurobiol Aging 2000; 21:741-746.[CrossRef][Medline] [Order article via Infotrieve]
  • 26. Pimlott SL, Piggott M, Owens J, et al. Nicotinic acetylcholine receptor distribution in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and vascular dementia: in vitro binding study using 5-[(125)i]-a-85380. Neuropsychopharmacology 2004; 29:108-116.[CrossRef][Medline] [Order article via Infotrieve]
  • 27. Court JA, Ballard CG, Piggott MA, et al. Visual hallucinations are associated with lower alpha bungarotoxin binding in dementia with Lewy bodies. Pharmacol Biochem Behav 2001; 70:571-579.[CrossRef][Medline] [Order article via Infotrieve]
  • 28. Ballard CG, Court JA, Piggott M, et al. Disturbances of consciousness in dementia with Lewy bodies associated with alteration in nicotinic receptor binding in the temporal cortex. Conscious Cogn 2002; 11:461-474.[CrossRef][Medline] [Order article via Infotrieve]
  • 29. Fagerstrom KO, Pomerleau O, Giordani B, Stelson F. Nicotine may relieve symptoms of Parkinson’s disease. Psychopharmacology (Berl) 1994; 116:117-119.[CrossRef][Medline] [Order article via Infotrieve]
  • 30. Kelton MC, Kahn HJ, Conrath CL, Newhouse PA. The effects of nicotine on Parkinson’s disease. Brain Cogn 2000; 43:274-282.[Medline] [Order article via Infotrieve]
  • 31. Vieregge A, Sieberer M, Jacobs H, et al. Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Neurology 2001; 57:1032-1035.[Abstract/Free Full Text]
  • 32. Hellstrom-Lindahl E, Moore H, Nordberg A. Increased levels of tau protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists. J Neurochem 2000; 74:777-784.[CrossRef][Medline] [Order article via Infotrieve]
  • 33. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000; 356:2031-2036.[CrossRef][Medline] [Order article via Infotrieve]
  • 34. Aarsland D, Laake K, Larsen JP, Janvin C. Donepezil for cognitive impairment in Parkinson’s disease: a randomised controlled study. J Neurol Neurosurg Psychiatry 2002; 72:708-712.[Abstract/Free Full Text]
  • 35. Leroi I, Brandt J, Reich SG, et al. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson’s disease. Int J Geriatr Psychiatry 2004; 19:1-8.[CrossRef][Medline] [Order article via Infotrieve]
  • 36. Herrmann M, Aarsland D, Albanese A, et al. EXPRESS: a prospective, placebo-controlled study of rivastigmine in Parkinson’s disease dementia. Presented at: 6th International AD/PD Conference, Sevilla, Spain, 2003.
  • 37. Fabbrini G, Barbanti P, Aurilia C, et al. Donepezil in the treatment of hallucinations and delusions in Parkinson’s disease. Neurol Sci 2002; 23:41-43.[CrossRef][Medline] [Order article via Infotrieve]
  • 38. Hutchinson M, Fazzini E. Cholinesterase inhibition in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1996; 61:324-325.
  • 39. Aarsland D, Hutchinson M, Larsen JP. Cognitive, psychiatric and motor response to galantamine in Parkinson’s disease with dementia. Int J Geriatr Psychiatry 2003; 18:937-941.[CrossRef][Medline] [Order article via Infotrieve]
  • 40. Grace J, Daniel S, Stevens T, et al. Long-term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial. Int Psychogeriatr 2001; 13:199-205.[CrossRef][Medline] [Order article via Infotrieve]
  • 41. Querfurth HW, Allam GJ, Geffroy MA, et al. Acetylcholinesterase inhibition in dementia with Lewy bodies: results of a prospective pilot trial. Dement Geriatr Cogn Disord 2000; 11:314-321.[Medline] [Order article via Infotrieve]
  • 42. Edwards KR, Hershey L, Wray L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 12-week interim analysis. Dement Geriatr Cogn Disord 2004; 17(suppl 1):40-48.
  • 43. Shea C, MacKnight C, Rockwood K. Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Int Psychogeriatr 1998; 10:229-238.[CrossRef][Medline] [Order article via Infotrieve]
  • 44. McKeith IG, Grace JB, Walker Z, et al. Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. Int J Geriatr Psychiatry 2000; 15:387-392.[CrossRef][Medline] [Order article via Infotrieve]
  • 45. Onofrj M, Thomas A. Severe worsening of parkinsonism in Lewy body dementia due to donepezil. Neurology 2003; 61:1452-1452.[Free Full Text]
  • 46. Burton EJ, McKeith IG, Burn DJ, et al. Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain 2004; 127:791-800.[Abstract/Free Full Text]
  • 47. Piggott MA, Owens J, O’Brien J, et al. Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease. J Chem Neuroanat 2003; 25:161-173.[CrossRef][Medline] [Order article via Infotrieve]
  • 48. Samuel W, Caligiuri M, Galasko D, et al. Better cognitive and psychopathologic response to donepezil in patients prospectively diagnosed as dementia with Lewy bodies: a preliminary study. Int J Geriatr Psychiatry 2000; 15:794-802.[CrossRef][Medline] [Order article via Infotrieve]
  • 49. Levy R, Eagger S, Griffiths M, et al. Lewy bodies and response to tacrine in Alzheimer’s disease. Lancet 1994; 343:176-176.[Medline] [Order article via Infotrieve]
  • 50. Perry EK, Kilford L, Lees AJ, et al. Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol 2003; 54:235-238.[CrossRef][Medline] [Order article via Infotrieve]
  • 51. Minett TS, Thomas A, Wilkinson LM, et al. What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson’s disease with dementia. Int J Geriatr Psychiatry 2003; 18:988-993.[CrossRef][Medline] [Order article via Infotrieve]
  • 52. Kulisevsky J, Garcia-Sanchez C, Berthier ML, et al. Chronic effects of dopaminergic replacement on cognitive function in Parkinson’s disease: a two-year follow-up study of previously untreated patients. Mov Disord 2000; 15:613-626.[Medline] [Order article via Infotrieve]
  • 53. Goetz CG, et al. Management of Parkinson’s disease. Mov Disord 2002; 17(suppl 4).
  • 54. McKeith I, Fairbairn A, Perry R, et al. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. Br Med J 1992; 305:673-678.
  • 55. Aarsland D, Perry R, Larsen JP, et al. High frequency of marked neuroleptic sensitivity in PD, PDD as well as in dementia with Lewy bodies with typical and atypical neuroleptic. Presented at: 3rd International Workshop on Dementia with Lewy Bodies and Parkinson’s Disease Dementia (DLB/PDD), Newcastle upon Tyne, UK, 2003.
  • 56. Kurita A, Ochiai Y, Kono Y, et al. The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson’s disease. J Geriatr Psychiatry Neurol 2003; 16:184-188.[Abstract]
  • 57. Reading PJ, Luce AK, McKeith IG. Rivastigmine in the treatment of parkinsonian psychosis and cognitive impairment: preliminary findings from an open trial. Mov Disord 2001; 16:1171-1174.[CrossRef][Medline] [Order article via Infotrieve]
  • 58. Bergman J, Lerner V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson’s disease. Clin Neuropharmacol 2002; 25:107-110.[CrossRef][Medline] [Order article via Infotrieve]
  • 59. Bullock R, Cameron A. Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson’s disease: a case series. Curr Med Res Opin 2002; 18:258-264.[CrossRef][Medline] [Order article via Infotrieve]
  • 60. Giladi N, Shabtai H, Gurevich T, et al. Rivastigmine (Exelon) for dementia in patients with Parkinson’s disease. Acta Neurol Scand 2003; 108:368-373.[Medline] [Order article via Infotrieve]
  • 61. Werber EA, Rabey JM. The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson’s disease and dementia. J Neural Transm 2001; 108:1319-1325.
  • 62. Wesnes KA, McKeith IG, Ferrara R, et al. 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 2002; 13:183-192.[CrossRef][Medline] [Order article via Infotrieve]
  • 63. Lebert F, Pasquier F, Souliez L, Petit H. Tacrine efficacy in Lewy body dementia. Int J Geriatr Psychiatry 1998; 13:516-519.[CrossRef][Medline] [Order article via Infotrieve]
  • 64. Maclean LE, Collins CC, Byrne EJ. Dementia with Lewy bodies treated with rivastigmine: effects on cognition, neuropsychiatric symptoms, and sleep. Int Psychogeriatr 2001; 13:277-288.[CrossRef][Medline] [Order article via Infotrieve]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Gerontol. A Biol. Sci. Med. Sci.Home page
J. A. H. R. Claassen and R. W. M. M. Jansen
Cholinergically mediated augmentation of cerebral perfusion in Alzheimer's disease and related cognitive disorders: the cholinergic-vascular hypothesis.
J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2006; 61(3): 267 - 271.
[Abstract] [Full Text] [PDF]


Home page
NeurologyHome page
I. G. McKeith, D. W. Dickson, J. Lowe, M. Emre, J. T. O'Brien, H. Feldman, J. Cummings, J. E. Duda, C. Lippa, E. K. Perry, et al.
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
Neurology, December 27, 2005; 65(12): 1863 - 1872.
[Abstract] [Full Text] [PDF]


Home page
AJGPHome page
D. Weintraub and M. B. Stern
Psychiatric Complications in Parkinson Disease
Am J Geriatr Psychiatry, October 1, 2005; 13(10): 844 - 851.
[Abstract] [Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aarsland, D.
Right arrow Articles by McKeith, I. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aarsland, D.
Right arrow Articles by McKeith, I. G.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?