Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2003 Jul;74(7):852–856. doi: 10.1136/jnnp.74.7.852

Lewy body cortical involvement may not always predict dementia in Parkinson's disease

C Colosimo 1, A Hughes 1, L Kilford 1, A Lees 1
PMCID: PMC1738521  PMID: 12810766

Abstract

Background: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB).

Methods: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records.

Results: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD.

Conclusions: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.

Full Text

The Full Text of this article is available as a PDF (107.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aarsland D., Ballard C., McKeith I., Perry R. H., Larsen J. P. Comparison of extrapyramidal signs in dementia with Lewy bodies and Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2001 Summer;13(3):374–379. doi: 10.1176/jnp.13.3.374. [DOI] [PubMed] [Google Scholar]
  2. Apaydin Hulya, Ahlskog J. Eric, Parisi Joseph E., Boeve Bradley F., Dickson Dennis W. Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response. Arch Neurol. 2002 Jan;59(1):102–112. doi: 10.1001/archneur.59.1.102. [DOI] [PubMed] [Google Scholar]
  3. Ballard C., O'Brien J., Swann A., Neill D., Lantos P., Holmes C., Burn D., Ince P., Perry R., McKeith I. One year follow-up of parkinsonism in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2000 Jul-Aug;11(4):219–222. doi: 10.1159/000017240. [DOI] [PubMed] [Google Scholar]
  4. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259. doi: 10.1007/BF00308809. [DOI] [PubMed] [Google Scholar]
  5. Brown R. G., Marsden C. D. Cognitive function in Parkinson's disease: from description to theory. Trends Neurosci. 1990 Jan;13(1):21–29. doi: 10.1016/0166-2236(90)90058-i. [DOI] [PubMed] [Google Scholar]
  6. Burkhardt C. R., Filley C. M., Kleinschmidt-DeMasters B. K., de la Monte S., Norenberg M. D., Schneck S. A. Diffuse Lewy body disease and progressive dementia. Neurology. 1988 Oct;38(10):1520–1528. doi: 10.1212/wnl.38.10.1520. [DOI] [PubMed] [Google Scholar]
  7. Byrne E. J., Lennox G., Lowe J., Godwin-Austen R. B. Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry. 1989 Jun;52(6):709–717. doi: 10.1136/jnnp.52.6.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Churchyard A., Lees A. J. The relationship between dementia and direct involvement of the hippocampus and amygdala in Parkinson's disease. Neurology. 1997 Dec;49(6):1570–1576. doi: 10.1212/wnl.49.6.1570. [DOI] [PubMed] [Google Scholar]
  9. Crystal H. A., Dickson D. W., Lizardi J. E., Davies P., Wolfson L. I. Antemortem diagnosis of diffuse Lewy body disease. Neurology. 1990 Oct;40(10):1523–1528. doi: 10.1212/wnl.40.10.1523. [DOI] [PubMed] [Google Scholar]
  10. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  11. Fénelon G., Mahieux F., Huon R., Ziégler M. Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors. Brain. 2000 Apr;123(Pt 4):733–745. doi: 10.1093/brain/123.4.733. [DOI] [PubMed] [Google Scholar]
  12. Galasko D., Katzman R., Salmon D. P., Hansen L. Clinical and neuropathological findings in Lewy body dementias. Brain Cogn. 1996 Jul;31(2):166–175. doi: 10.1006/brcg.1996.0040. [DOI] [PubMed] [Google Scholar]
  13. Gibb W. R., Esiri M. M., Lees A. J. Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain. 1987 Oct;110(Pt 5):1131–1153. doi: 10.1093/brain/110.5.1131. [DOI] [PubMed] [Google Scholar]
  14. Gibb W. R., Lees A. J. The significance of the Lewy body in the diagnosis of idiopathic Parkinson's disease. Neuropathol Appl Neurobiol. 1989 Jan-Feb;15(1):27–44. doi: 10.1111/j.1365-2990.1989.tb01147.x. [DOI] [PubMed] [Google Scholar]
  15. Gnanalingham K. K., Byrne E. J., Thornton A., Sambrook M. A., Bannister P. Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's diseases. J Neurol Neurosurg Psychiatry. 1997 Mar;62(3):243–252. doi: 10.1136/jnnp.62.3.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gómez-Isla T., Growdon W. B., McNamara M., Newell K., Gómez-Tortosa E., Hedley-Whyte E. T., Hyman B. T. Clinicopathologic correlates in temporal cortex in dementia with Lewy bodies. Neurology. 1999 Dec 10;53(9):2003–2009. doi: 10.1212/wnl.53.9.2003. [DOI] [PubMed] [Google Scholar]
  17. Gómez-Tortosa E., Newell K., Irizarry M. C., Albert M., Growdon J. H., Hyman B. T. Clinical and quantitative pathologic correlates of dementia with Lewy bodies. Neurology. 1999 Oct 12;53(6):1284–1291. doi: 10.1212/wnl.53.6.1284. [DOI] [PubMed] [Google Scholar]
  18. Gómez-Tortosa E., Newell K., Irizarry M. C., Sanders J. L., Hyman B. T. alpha-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining. Acta Neuropathol. 2000 Apr;99(4):352–357. doi: 10.1007/s004010051135. [DOI] [PubMed] [Google Scholar]
  19. Harding A. J., Halliday G. M. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol. 2001 Oct;102(4):355–363. doi: 10.1007/s004010100390. [DOI] [PubMed] [Google Scholar]
  20. Harding A. J., Halliday G. M. Simplified neuropathological diagnosis of dementia with Lewy bodies. Neuropathol Appl Neurobiol. 1998 Jun;24(3):195–201. doi: 10.1046/j.1365-2990.1998.00115.x. [DOI] [PubMed] [Google Scholar]
  21. Hughes A. J., Daniel S. E., Blankson S., Lees A. J. A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol. 1993 Feb;50(2):140–148. doi: 10.1001/archneur.1993.00540020018011. [DOI] [PubMed] [Google Scholar]
  22. Hurtig H. I., Trojanowski J. Q., Galvin J., Ewbank D., Schmidt M. L., Lee V. M., Clark C. M., Glosser G., Stern M. B., Gollomp S. M. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease. Neurology. 2000 May 23;54(10):1916–1921. doi: 10.1212/wnl.54.10.1916. [DOI] [PubMed] [Google Scholar]
  23. Irizarry M. C., Growdon W., Gomez-Isla T., Newell K., George J. M., Clayton D. F., Hyman B. T. Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. J Neuropathol Exp Neurol. 1998 Apr;57(4):334–337. doi: 10.1097/00005072-199804000-00005. [DOI] [PubMed] [Google Scholar]
  24. Kaufer D. I., Catt K. E., Lopez O. L., DeKosky S. T. Dementia with Lewy bodies: response of delirium-like features to donepezil. Neurology. 1998 Nov;51(5):1512–1512. doi: 10.1212/wnl.51.5.1512. [DOI] [PubMed] [Google Scholar]
  25. Klatka L. A., Louis E. D., Schiffer R. B. Psychiatric features in diffuse Lewy body disease: a clinicopathologic study using Alzheimer's disease and Parkinson's disease comparison groups. Neurology. 1996 Nov;47(5):1148–1152. doi: 10.1212/wnl.47.5.1148. [DOI] [PubMed] [Google Scholar]
  26. Kosaka K., Tsuchiya K., Yoshimura M. Lewy body disease with and without dementia: a clinicopathological study of 35 cases. Clin Neuropathol. 1988 Nov-Dec;7(6):299–305. [PubMed] [Google Scholar]
  27. Lang A. E., Lozano A. M. Parkinson's disease. First of two parts. N Engl J Med. 1998 Oct 8;339(15):1044–1053. doi: 10.1056/NEJM199810083391506. [DOI] [PubMed] [Google Scholar]
  28. Lennox G., Lowe J., Landon M., Byrne E. J., Mayer R. J., Godwin-Austen R. B. Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry. J Neurol Neurosurg Psychiatry. 1989 Nov;52(11):1236–1247. doi: 10.1136/jnnp.52.11.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lippa C. F., Smith T. W., Perry E. Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology. J Neural Transm (Vienna) 1999;106(5-6):525–535. doi: 10.1007/s007020050176. [DOI] [PubMed] [Google Scholar]
  30. Lippa C. F., Smith T. W., Swearer J. M. Alzheimer's disease and Lewy body disease: a comparative clinicopathological study. Ann Neurol. 1994 Jan;35(1):81–88. doi: 10.1002/ana.410350113. [DOI] [PubMed] [Google Scholar]
  31. Louis E. D., Klatka L. A., Liu Y., Fahn S. Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's disease. Neurology. 1997 Feb;48(2):376–380. doi: 10.1212/wnl.48.2.376. [DOI] [PubMed] [Google Scholar]
  32. Mackenzie I. R. Activated microglia in dementia with Lewy bodies. Neurology. 2000 Jul 12;55(1):132–134. doi: 10.1212/wnl.55.1.132. [DOI] [PubMed] [Google Scholar]
  33. Mattila P. M., Röyttä M., Torikka H., Dickson D. W., Rinne J. O. Cortical Lewy bodies and Alzheimer-type changes in patients with Parkinson's disease. Acta Neuropathol. 1998 Jun;95(6):576–582. doi: 10.1007/s004010050843. [DOI] [PubMed] [Google Scholar]
  34. McKeith I. G., Fairbairn A. F., Perry R. H., Thompson P. The clinical diagnosis and misdiagnosis of senile dementia of Lewy body type (SDLT). Br J Psychiatry. 1994 Sep;165(3):324–332. doi: 10.1192/bjp.165.3.324. [DOI] [PubMed] [Google Scholar]
  35. McKeith I. G., Galasko D., Kosaka K., Perry E. K., Dickson D. W., Hansen L. A., Salmon D. P., Lowe J., Mirra S. S., Byrne E. J. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124. doi: 10.1212/wnl.47.5.1113. [DOI] [PubMed] [Google Scholar]
  36. McKeith I. G., Perry E. K., Perry R. H. Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on Dementia with Lewy Bodies. Neurology. 1999 Sep 22;53(5):902–905. doi: 10.1212/wnl.53.5.902. [DOI] [PubMed] [Google Scholar]
  37. McKeith I., Del Ser T., Spano P., Emre M., Wesnes K., Anand R., Cicin-Sain A., Ferrara R., Spiegel R. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000 Dec 16;356(9247):2031–2036. doi: 10.1016/S0140-6736(00)03399-7. [DOI] [PubMed] [Google Scholar]
  38. Mirra S. S., Heyman A., McKeel D., Sumi S. M., Crain B. J., Brownlee L. M., Vogel F. S., Hughes J. P., van Belle G., Berg L. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991 Apr;41(4):479–486. doi: 10.1212/wnl.41.4.479. [DOI] [PubMed] [Google Scholar]
  39. Perry R. H., Irving D., Blessed G., Fairbairn A., Perry E. K. Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci. 1990 Feb;95(2):119–139. doi: 10.1016/0022-510x(90)90236-g. [DOI] [PubMed] [Google Scholar]
  40. Pompeu Fernando, Growdon John H. Diagnosing dementia with Lewy bodies. Arch Neurol. 2002 Jan;59(1):29–30. doi: 10.1001/archneur.59.1.29. [DOI] [PubMed] [Google Scholar]
  41. Richard Irene Hegeman, Papka Michelle, Rubio Ana, Kurlan Roger. Parkinson's disease and dementia with Lewy bodies: one disease or two? Mov Disord. 2002 Nov;17(6):1161–1165. doi: 10.1002/mds.10274. [DOI] [PubMed] [Google Scholar]
  42. Rozemuller A. J., Eikelenboom P., Theeuwes J. W., Jansen Steur E. N., de Vos R. A. Activated microglial cells and complement factors are unrelated to cortical Lewy bodies. Acta Neuropathol. 2000 Dec;100(6):701–708. doi: 10.1007/s004010000225. [DOI] [PubMed] [Google Scholar]
  43. Salmon D. P., Galasko D., Hansen L. A., Masliah E., Butters N., Thal L. J., Katzman R. Neuropsychological deficits associated with diffuse Lewy body disease. Brain Cogn. 1996 Jul;31(2):148–165. doi: 10.1006/brcg.1996.0039. [DOI] [PubMed] [Google Scholar]
  44. Samuel W., Galasko D., Masliah E., Hansen L. A. Neocortical lewy body counts correlate with dementia in the Lewy body variant of Alzheimer's disease. J Neuropathol Exp Neurol. 1996 Jan;55(1):44–52. doi: 10.1097/00005072-199601000-00005. [DOI] [PubMed] [Google Scholar]
  45. Shepherd C. E., Thiel E., McCann H., Harding A. J., Halliday G. M. Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies. Arch Neurol. 2000 Jun;57(6):817–822. doi: 10.1001/archneur.57.6.817. [DOI] [PubMed] [Google Scholar]
  46. Spillantini M. G., Schmidt M. L., Lee V. M., Trojanowski J. Q., Jakes R., Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997 Aug 28;388(6645):839–840. doi: 10.1038/42166. [DOI] [PubMed] [Google Scholar]
  47. Takeda A., Mallory M., Sundsmo M., Honer W., Hansen L., Masliah E. Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. Am J Pathol. 1998 Feb;152(2):367–372. [PMC free article] [PubMed] [Google Scholar]
  48. Tompkins M. M., Hill W. D. Contribution of somal Lewy bodies to neuronal death. Brain Res. 1997 Nov 14;775(1-2):24–29. doi: 10.1016/s0006-8993(97)00874-3. [DOI] [PubMed] [Google Scholar]
  49. Trojanowski J. Q., Lee V. M. Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for the pathogenesis of Parkinson disease and Lewy body dementia. Arch Neurol. 1998 Feb;55(2):151–152. doi: 10.1001/archneur.55.2.151. [DOI] [PubMed] [Google Scholar]
  50. Vermersch P., Delacourte A., Javoy-Agid F., Hauw J. J., Agid Y. Dementia in Parkinson's disease: biochemical evidence for cortical involvement using the immunodetection of abnormal Tau proteins. Ann Neurol. 1993 May;33(5):445–450. doi: 10.1002/ana.410330506. [DOI] [PubMed] [Google Scholar]
  51. Wakabayashi K., Hansen L. A., Masliah E. Cortical Lewy body-containing neurons are pyramidal cells: laser confocal imaging of double-immunolabeled sections with anti-ubiquitin and SMI32. Acta Neuropathol. 1995;89(5):404–408. doi: 10.1007/BF00307643. [DOI] [PubMed] [Google Scholar]
  52. Zweig R. M., Cardillo J. E., Cohen M., Giere S., Hedreen J. C. The locus ceruleus and dementia in Parkinson's disease. Neurology. 1993 May;43(5):986–991. doi: 10.1212/wnl.43.5.986. [DOI] [PubMed] [Google Scholar]
  53. de Vos R. A., Jansen E. N., Stam F. C., Ravid R., Swaab D. F. 'Lewy body disease': clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia. Clin Neurol Neurosurg. 1995 Feb;97(1):13–22. doi: 10.1016/0303-8467(94)00060-j. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES