Lewy body dementia and Parkinson’s disease with dementia

Abstract

Parkinson’s disease (PD) is characterized by its motor impairment. However, non-motor symptoms such as psychiatric disorders, autonomic disturbances and sleep disorders frequently complicate the course of the disease. In particular, psychiatric disturbances including cognitive impairment, depression and psychosis impact these patients considerably. Approximately 31 % of PD patients suffer from cognitive impairment and dementia. Currently, two different clinical presentations are distinguished in PD patients, who present with dementia: Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB), which are two different presentations of a single underlying disease process leading to the deposition of α-synuclein. Clinically, PDD is distinguished from DLB alone by the different temporal manifestations of extrapyramidal motor symptoms. Dementia is characterized by a subtle onset and progressive cognitive decline with a predominant dysexecutive syndrome, which can be accompanied by different behavioral symptoms such as hallucinations, depression, anxiety and sleep disorders. Dysregulation of different neurotransmitters has been associated with cognitive decline, but reduced cholinergic transmission is currently thought to be the pivotal mechanism in the development of cognitive dysfunction. Therefore, cholinesterase inhibitors are used in the treatment of dementia and accompanying behavioral symptoms in PDD and DLB. The occurrence of dementia impacts not only the patients themselves but also their care-givers and family.

This article focuses on the clinical issues related to both disorders and is based on a meeting of experts which took place in April 2008 in Dresden.

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

References

  1. 1.

    Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P (2003) Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 60:387–392

    PubMed  Article  Google Scholar 

  2. 2.

    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 

  3. 3.

    Aarsland D, Zaccai J, Brayne C (2005) A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 20:1255–1263

    PubMed  Article  Google Scholar 

  4. 4.

    Bostrom F, Jonsson L, Minthon L, Londos E (2007) Patients with dementia with lewy bodies have more impaired quality of life than patients with Alzheimer disease. Alzheimer Dis Assoc Disord 21:150–154

    PubMed  Article  Google Scholar 

  5. 5.

    Boström F, Jönsson L, Minthon L, Londos E (2007) Patients with dementia with lewy bodies have more impaired quality of life than patients with Alzheimer disease. Alzheimer Dis Assoc Disord 21:150–154

    PubMed  Article  Google Scholar 

  6. 6.

    Brand S, Dodel R, Hautzinger M, Grunder G, Althaus A, Schneider F (2007) Depression in Parkinson’s disease. Assessment and treatment. Nervenarzt 78:715–727; quiz 728

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Briel RC, McKeith IG, Barker WA, Hewitt Y, Perry RH, Ince PG, Fairbairn AF (1999) EEG findings in dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 66:401–403

    PubMed  CAS  Google Scholar 

  8. 8.

    Caballol N, Marti MJ, Tolosa E (2007) Cognitive dysfunction and dementia in Parkinson disease. Mov Disord 22(Suppl 17):S358–S366

    Article  Google Scholar 

  9. 9.

    Del-Ser T, Munoz DG, Hachinski V (1996) Temporal pattern of cognitive decline and incontinence is different in Alzheimer’s disease and diffuse Lewy body disease. Neurology 46:682–686

    PubMed  CAS  Google Scholar 

  10. 10.

    Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R (2004) Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 351:2509–2518

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707; quiz 1837

    PubMed  Article  Google Scholar 

  12. 12.

    Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J (2006) Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 5:424–432

    PubMed  Article  Google Scholar 

  13. 13.

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

    PubMed  CAS  Google Scholar 

  14. 14.

    Goldmann Gross R, Siderowf A, Hurtig HI (2008) Cognitive impairment in Parkinson’s disease and dementia with lewy bodies: a spectrum of disease. Neurosignals 16:24–34

    Article  CAS  Google Scholar 

  15. 15.

    Hickey C, Chisholm T, Passmore MJ, O’Brien JD, Johnston J (2008) Differentiating the dementias. Revisiting synucleinopathies and tauopathies. Current Alzheimer Research 5:52–60

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Hu XS, Okamura N, Arai H, Higuchi M, Matsui T, Tashiro M, Shinkawa M, Itoh M, Ido T, Sasaki H (2000) 18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies. Neurology 55:1575–1577

    PubMed  CAS  Google Scholar 

  17. 17.

    Jellinger KA (2006) Neuropathology of dementia in Parkinson’s disease. Ann Neurol 59:727

    PubMed  Article  Google Scholar 

  18. 18.

    Kalbe E, Calabrese P, Kohn N, Hilker R, Riedel O, Wittchen HU, Dodel R, Otto J, Ebersbach G, Kessler J (2008) Screening for cognitive deficits in Parkinson’s disease with the Parkinson neuropsychometric dementia assessment (PANDA) instrument. Parkinsonism Relat Disord 14:93–101

    PubMed  Article  Google Scholar 

  19. 19.

    Lemke MR (2008) Depressive symptoms in Parkinson’s disease. Eur J Neurol 15(Suppl 1):21–25

    PubMed  Article  Google Scholar 

  20. 20.

    Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF, Brooks DJ, Dickson DW, Dubois B, Emre M, Fahn S, Farmer JM, Galasko D, Galvin JE, Goetz CG, Growdon JH, Gwinn-Hardy KA, Hardy J, Heutink P, Iwatsubo T, Kosaka K, Lee VM, Leverenz JB, Masliah E, McKeith IG, Nussbaum RL, Olanow CW, Ravina BM, Singleton AB, Tanner CM, Trojanowski JQ, Wszolek ZK (2007) DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68:812–819

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Lobotesis K, Fenwick JD, Phipps A, Ryman A, Swann A, Ballard C, McKeith IG, O’Brien JT (2001) Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 56:643–649

    PubMed  CAS  Google Scholar 

  22. 22.

    Lopez OL, Wisniewski S, Hamilton RL, Becker JT, Kaufer DI, DeKosky ST (2000) Predictors of progression in patients with AD and Lewy bodies. Neurology 54:1774–1779

    PubMed  CAS  Google Scholar 

  23. 23.

    Maetzler W, Reimold M, Liepelt I, Solbach C, Leyhe T, Schweitzer K, Eschweiler GW, Mittelbronn M, Gaenslen A, Uebele M, Reischl G, Gasser T, Machulla HJ, Bares R, Berg D (2008) [11C]PIB binding in Parkinson’s disease dementia. NeuroImage 39:1027–1033

    PubMed  Article  Google Scholar 

  24. 24.

    Maidment I, Fox C, Boustani M (2006) Cholinesterase inhibitors for Parkinson’s disease dementia. Cochrane database of systematic reviews (Online):CD004747

  25. 25.

    McKeith I (2007) Dementia with Lewy bodies and Parkinson’s disease with dementia: where two worlds collide. Practical Neurology 7:374–382

    PubMed  Article  CAS  Google Scholar 

  26. 26.

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

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    McKeith I, Fairbairn A, Perry R, Thompson P, Perry E (1992) Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ (Clinical research ed) 305:673–678

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O’Brien J, Playfer J, Reid W (2004) Dementia with Lewy bodies. Lancet Neurology 3:19–28

    PubMed  Article  Google Scholar 

  29. 29.

    McKeith IG, Dickson DW, Lowe J, Emre M, O‘Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Mollenhauer B, Bibl M, Wiltfang J, Steinacker P, Ciesielczyk B, Neubert K, Trenkwalder C, Otto M (2006) Total tau protein, phosphorylated tau (181p) protein, beta-amyloid(1–42), and betaamyloid(1–40) in cerebrospinal fluid of patients with dementia with Lewy bodies. Clin Chem Lab Med 44:192–195

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Morgante L, Epifanio A, Spina E, Zappia M, Di Rosa AE, Marconi R, Basile G, Di Raimondo G, La Spina P, Quattrone A (2004) Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol 27:153–156

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Mosimann UP, Mather G, Wesnes KA, O‘Brien JT, Burn DJ, McKeith IG (2004) Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology 63:2091–2096

    PubMed  CAS  Google Scholar 

  33. 33.

    Olichney JM, Galasko D, Salmon DP, Hofstetter CR, Hansen LA, Katzman R, Thal LJ (1998) Cognitive decline is faster in Lewy body variant than in Alzheimer’s disease. Neurology 51:351–357

    PubMed  CAS  Google Scholar 

  34. 34.

    Otto M, Lewczuk P, Wiltfang J (2008) Neurochemical approaches of cerebrospinal fluid diagnostics in neurodegenerative diseases. Methods (San Diego, CA) 44:289–298

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Poewe W (2007) Dysautonomia and cognitive dysfunction in Parkinson’s disease. Mov Disord 22(Suppl 17):S374–S378

    Article  Google Scholar 

  36. 36.

    Riedel O, Klotsche J, Spottke A, Deuschl G, Forstl H, Henn F, Heuser I, Oertel W, Reichmann H, Riederer P, Trenkwalder C, Dodel R, Wittchen HU (2008) Cognitive impairment in 873 patients with idiopathic Parkinson’s disease. Results from the German Study on Epidemiology of Parkinson’s Disease with Dementia (GEPAD). J Neurol 255:255–264

    PubMed  Article  Google Scholar 

  37. 37.

    Shabnam GN, Th C, Kho D, H R, Ce C (2003) Therapies for depression in Parkinson’s disease. Cochrane database of systematic reviews (Online):CD003465

  38. 38.

    Tokuda T, Salem SA, Allsop D, Mizuno T, Nakagawa M, Qureshi MM, Locascio JJ, Schlossmacher MG, El-Agnaf OM (2006) Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’ disease. Biochem Biophys Res Commun 349:162–166

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, Livingston G, Ince P, McKeith IG, Katona CL (2002) Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 73:134-140

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Weintraub D, Morales KH, Moberg PJ, Bilker WB, Balderston C, Duda JE, Katz IR, Stern MB (2005) Antidepressant studies in Parkinson’s disease: a review and meta-analysis. Mov Disord 20:1161–1169

    PubMed  Article  Google Scholar 

  41. 41.

    Zaccai J, McCracken C, Brayne C (2005) A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 34:561–566

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Richard Dodel.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Dodel, R., Csoti, I., Ebersbach, G. et al. Lewy body dementia and Parkinson’s disease with dementia. J Neurol 255, 39 (2008). https://doi.org/10.1007/s00415-008-5007-0

Download citation

Key words

  • Parkinson’s disease
  • dementia with Lewy bodies
  • dementia
  • α-synuclein
  • cholinesterase inhibitors