Log in / Register
Home arrow Health arrow Cognitive impairment and dementia in Parkinson disease


Dementia is common in PD, especially as the disease progresses and patients get older. In its pure form, dementia in PD occurs when LB pathology spreads to involve cortical and limbic structures. In addition, many PD-D patients have concurrent AD or vascular changes. Clinicians will observe slightly different cognitive features in the different pathological forms that occur across the PD-D spectrum. The regional distribution of pathology will correlate with symptoms. For example, patients with ‘pure PD-D’ solely associated with LB pathology are less likely to experience a primarily amnestic dementia. When amnesia is a prominent feature, concurrent AD pathology is likely, beginning in medial temporal lobe regions that are key for forming new memories. Overall, there is clinical and pathological heterogeneity amongst PD-D patients. With an eye toward aetiologically based treatments, it will become more important to identify the biological factors involved in the development of dementia in each PD patient.


  • 1. Parkinson J. An essay on the shaking palsy. London: Whittingham & Rowland, 1817. [Annotated reprint in Med Classics 1938; 2: 957-98.]
  • 2. Goldmann Gross R, Siderowf A, Hurtig HI. Cognitive impairment in Parkinson’s disease and dementia with Lewy bodies: a spectrum of disease. Neurosignals 2008; 16: 24-34.
  • 3. Aarsland D, Andersen K, Larsen JP, et al. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003; 60: 387-92.
  • 4. Cummings JL. The dementias of Parkinson’s disease: prevalence, characteristics, neurobiology, and comparison with dementia of the Alzheimer type. Eur Neurol 1988; 28(Suppl. 1): 15-23.
  • 5. Emre M. Dementia in Parkinson’s disease: cause and treatment. Curr Opin Neurol 2004; 17: 399-404.
  • 6. Lewy F. Zur pathologischen Anatomie der Paralysis agitans. Dtsch Z Nervenheilk 1914; 1: 50-5.
  • 7. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997; 276: 2045-7.
  • 8. Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-40.
  • 9. Baba M, Nakajo S, Tu PH, et al. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 1998; 152: 879-84.
  • 10. Shults CW. Lewy bodies. Proc Natl Acad Sci USA 2006; 103: 1661-8.
  • 11. Galvin JE, Lee VM, Trojanowski JQ. Synucleinopathies: clinical and pathological implications. Arch Neurol 2001; 58: 186-90.
  • 12. Aarsland D, Perry R, Brown A, et al. Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 2005; 58: 773-6.
  • 13. Hurtig HI, Trojanowski JQ, Galvin J, et al. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 2000; 54: 1916-21.
  • 14. Kovari E, Gold G, Herrmann FR, et al. Lewy body densities in the entorhinal and anterior cingulate cortex predict cognitive deficits in Parkinson’s disease. Acta Neuropathol 2003; 106: 83-8.
  • 15. Iqbal K, Grundke-Iqbal I. Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective. J Alzheimers Dis 2006; 9: 219-42.
  • 16. Boeve BF, Hutton M. Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol 2008; 65: 460-4.
  • 17. Ballard C, Ziabreva I, Perry R, et al. Differences in neuropathologic characteristics across the Lewy body dementia spectrum. Neurology 2006; 67: 1931-4.
  • 18. Sabbagh MN, Adler CH, Lahti TJ, et al. Parkinson disease with dementia: comparing patients with and without Alzheimer pathology. Alzheimer Dis Assoc Disord 2009; 23: 295-7.
  • 19. Colom-Cadena M, Gelpi E, Charif S, et al. Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. J Neuropathol Exp Neurol 2013; 72: 1203-12.
  • 20. Williams-Gray CH, Goris A, Saiki M, et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. J Neurol 2009; 256: 493-8.
  • 21. Polvikoski T, Sulkava R, Haltia M, et al. Apolipoprotein E, dementia, and cortical deposition of beta- amyloid protein. N Engl J Med 1995; 333: 1242-7.
  • 22. Laws SM, Friedrich P, Diehl-Schmid J, et al. Fine mapping of the MAPT locus using quantitative trait analysis identifies possible causal variants in Alzheimer’s disease. Mol Psychiatry 2007; 12: 510-17.
  • 23. Compta Y, Parkkinen L, O’Sullivan SS, et al. Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain 2011; 134: 1493-505.
  • 24. Tretiakoff C. Contribution a letude de l’anatomie pathologique du locus niger de Soemmering avec quelques dedutions relatives a la pathogenie des troubles du tonus musculaire et de la maladie de Parkinson. Thesis. University of Paris, 1919.
  • 25. Jellinger KA. A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol 2008; 116: 1-16.
  • 26. Ma SY, Roytta M, Rinne JO, et al. Correlation between neuromorphometry in the substantia nigra and clinical features in Parkinson’s disease using dissector counts. J Neurol Sci 1997; 151: 83-7.
  • 27. Duda JE, Giasson BI, Mabon ME, et al. Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann Neurol 2002; 52: 205-10.
  • 28. Lippa CF, Duda JE, Grossman M, et al. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007; 68: 812-19.
  • 29. Li JY, Englund E, Holton JL, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14: 501-3.
  • 30. Harding AJ, Halliday GM. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuro- pathol 2001; 102: 355-63.
  • 31. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain 2002; 125: 391-403.
  • 32. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65: 1863-72.
  • 33. Merdes AR, Hansen LA, Jeste DV, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 2003; 60: 1586-90.
  • 34. Fujishiro H, Ferman TJ, Boeve BF, et al. Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases. J Neuropathol Exp Neurol 2008; 67: 649-56.
  • 35. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211.
  • 36. Braak H, Rub U, Jansen Steur EN, et al. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 2005; 64: 1404-10.
  • 37. Colosimo C, Hughes AJ, Kilford L, et al. Lewy body cortical involvement may not always predict dementia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003; 74: 852-6.
  • 38. Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 2007; 33: 599-614.
  • 39. Halliday G, Hely M, Reid W, et al. The progression of pathology in longitudinally followed patients with Parkinson’s disease. Acta Neuropathol 2008; 115: 409-15.
  • 40. Jellinger KA. A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta 2009; 1792: 730-40.
  • 41. Alafuzoff I, Ince PG, Arzberger T, et al. Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol 2009; 117: 635-52.
  • 42. Muller CM, de Vos RA, Maurage CA, et al. Staging of sporadic Parkinson disease-related alpha-synu- clein pathology: inter- and intra-rater reliability. J Neuropathol Exp Neurol 2005; 64: 623-8.
  • 43. Leverenz JB, Hamilton R, Tsuang DW, et al. Empiric refinement of the pathologic assessment of Lewy- related pathology in the dementia patient. Brain Pathol 2008; 18: 220-4.
  • 44. Compta Y, Parkkinen L, Kempster P, et al. The significance of alpha-synuclein, amyloid-beta and tau pathologies in Parkinson’s disease progression and related dementia. Neurodegener Dis 2014; 13: 154-6.
  • 45. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007; 6: 734-46.
  • 46. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010; 9: 1118-27.
  • 47. Buongiorno M, Compta Y, Marti MJ. Amyloid-beta and tau biomarkers in Parkinson’s disease-dementia. J Neurol Sci 2011; 310: 25-30.
  • 48. Brundin P, Li JY, Holton JL, et al. Research in motion: the enigma of Parkinson’s disease pathology spread. Nat Rev Neurosci 2008; 9: 741-5.
Found a mistake? Please highlight the word and press Shift + Enter  
< Prev   CONTENTS   Next >
Business & Finance
Computer Science
Language & Literature
Political science