Pathological diagnostic criteria for dementia associated with cortical Lewy bodies: review and proposal for a descriptive approach

  • J. Lowe
  • D. Dickson
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 51)


In recent years dementia histologically characterised by the presence of cortical Lewy bodies has been increasingly recognised. There is now need for a scheme for an internationally acceptable scheme for pathological diagnosis and classification so that clinical, pathological and molecular features of disease can be correlated. Recent observations made by different groups in large patient series have used slightly different pathological criteria resulting in at least seven different diagnostic terms. In some patients the only cortical pathology is the presence of Lewy bodies, while in the majority of patients there are coexisting pathological changes which either overlap with those seen in Alzheimer’s disease (AD). Cortical Lewy bodies can also be present in patients who do not have any obvious cognitive abnormality. A problem with equating studies from different groups is that different criteria have been used to define AD, so that establishing the relevance of cortical Lewy bodies themselves to cognitive decline and separating this from the contribution which may be related to the AD pathology is problematic. The lesions which appear to be of most relevance to potential cognitive decline in DLB are cortical Lewy bodies, Lewy-related neurites, senile plaques, neurofibrillary tangles, neuronal and synaptic loss, spongiform change, and cortical cholinergic deficits. It is possible to operationally classify patients with cognitive decline and cortical Lewy bodies into three main groups, Cortical Lewy body disease, Cortical Lewy body disease with plaques, and Cortical Lewy body disease with plaques and tangles. There are frequent cases which overlap these groups making operational classification difficult in practice. A descriptive classification, in which the severity of different pathological changes is rated, is easy to use in practice. As new molecular risk factors for AD or DLB are revealed they will need to be related to morphological and clinical features. A descriptive diagnostic assessment for DLB will facilitate such studies and makes no judgements as to what these relationships will be.


Lewy Body Senile Dementia Lewy Body Disease Lewy Body Dementia Lewy Body Pathology 
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  1. Armstrong TP, Hansen LA, Salmon DP, Masliah E, et al. (1991) Rapidly progressive dementia in a patient with the Lewy body variant of Alzheimer’s disease. Neurology 41(8): 1178–1180.PubMedCrossRefGoogle Scholar
  2. Bancher C, Braak H, Fischer P, Jellinger KA (1993) Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer’s and Parkinson’s disease patients. Neurosci Lett 162(1–2): 179–182.PubMedCrossRefGoogle Scholar
  3. Benjamin R, Leake A, Edwardson JA, McKeith IG, et al. (1994) Apolipoprotein E genes in Lewy body and Parkinson’s disease. Lancet 343(8912): 1565.PubMedCrossRefGoogle Scholar
  4. Betard C, Robitaille Y, Gee M, Tiberghien D, et al. (1994) Apo E allele frequencies in Alzheimer’s disease, Lewy body dementia, Alzheimer’s disease with cerebrovascular disease and vascular dementia. Neuroreport 5(15): 1893–1896.PubMedCrossRefGoogle Scholar
  5. Bodhireddy S, Dickson DW, Mattiace L, Weidenheim KM (1994) A case of Down’s syndrome with diffuse Lewy body disease and Alzheimer’s disease. Neurology 44(1): 159–161.PubMedCrossRefGoogle Scholar
  6. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Beri) 82(4): 239–259.CrossRefGoogle Scholar
  7. Braak H, Braak E, Yilmazer D, de Vos RA, et al. (1994) Amygdala pathology in Parkinson’s disease. Acta Neuropathol (Beri) 88(6): 493–500.CrossRefGoogle Scholar
  8. Burkhardt CR, Filley CM, Kleinschmidt-De Masters BK, de la Monte S, et al. (1988) Diffuse Lewy body disease and progressive dementia. Neurology 38(10): 1520–1528.PubMedCrossRefGoogle Scholar
  9. Byrne EJ, Lowe J, Godwin-Austen RB, Arie T, et al. (1987) Dementia and Parkinson’s disease associated with diffuse cortical Lewy bodies. Lancet i (8531): 501.CrossRefGoogle Scholar
  10. Byrne EJ, Lennox G, Lowe J, Godwin-Austen RB (1989) Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry 52(6): 709–717.PubMedCrossRefGoogle Scholar
  11. Byrne E, Lennox G, Godwin-Austen R, Mayer R, et al. (1991) Diagnostic criteria for dementia associated with cortical Lewy bodies. Dementia 2: 283–284.Google Scholar
  12. Clark AW, White CLd, Manz HJ, Parhad IM, et al. (1986) Primary degenerative dementia without Alzheimer pathology. Can J Neurol Sci 13 [4 Suppl]: 462–470.PubMedGoogle Scholar
  13. Crystal HA, Dickson DW, Lizardi JE, Davies P, et al. (1990) Antemortem diagnosis of diffuse Lewy body disease. Neurology 40(10): 1523–1528.PubMedCrossRefGoogle Scholar
  14. de Bruin VM, Lees AJ, Daniel SE (1992) Diffuse Lewy body disease presenting with supranuclear gaze palsy, parkinsonism, and dementia: a case report. Mov Disord 7(4): 355–358.PubMedCrossRefGoogle Scholar
  15. de Vos RA, Jansen EN, Stam FC, Ravid R, et al. (1995) “Lewy body disease”: clinico-pathological correlations in 18 consecutive cases of Parkinson’s disease with and without dementia. Clin Neurol Neurosurg 97(1): 13–22.PubMedCrossRefGoogle Scholar
  16. Dickson DW, Davies P, Mayeux R, Crystal H, et al. (1987) Diffuse Lewy body disease. Neuropathological and biochemical studies of six patients. Acta Neuropathol (Berl) 75(1): 8–15.CrossRefGoogle Scholar
  17. Dickson DW, Crystal H, Mattiace LA, Kress Y, et al. (1989) Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques. Acta Neuropathol (Beri) 78(6): 572–584.CrossRefGoogle Scholar
  18. Dickson DW, Ruan D, Crystal H, Mark MH, et al. (1991) Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer’s disease: light and electron microscopic immunocytochemistry of CA2–3 neurites specific to DLBD. Neurology 41(9): 1402–1409.PubMedCrossRefGoogle Scholar
  19. Dickson DW, Schmidt ML, Lee VM, Zhao ML, et al. (1994) Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. Acta Neuropathol (Berl) 87(3): 269–276.CrossRefGoogle Scholar
  20. Duvoisin RC, Johnson WG (1992) Hereditary Lewy-body parkinsonism and evidence for a genetic etiology of Parkinson’s disease. Brain Pathol 2(4): 309–320.PubMedCrossRefGoogle Scholar
  21. Eggertson DE, Sima AA (1986) Dementia with cerebral Lewy bodies. A mesocortical dopaminergic defect? Arch Neurol 43(5): 524–527.PubMedCrossRefGoogle Scholar
  22. Fearnley JM, Revesz T, Brooks DJ, Frackowiak RS, et al. (1991) Diffuse Lewy body disease presenting with a supranuclear gaze palsy. J Neurol Neurosurg Psychiatry 54(2): 159–161.PubMedCrossRefGoogle Scholar
  23. Gai WP, Blessing WW, Blumbergs PC (1995) Ubiquitin-positive degenerating neurites in the brainstem in Parkinson’s disease. Brain 118(6): 1447–1459.PubMedCrossRefGoogle Scholar
  24. Galasko D, Saitoh T, Xia Y, Thal LJ, et al. (1994) The apolipoprotein E allele epsilon 4 is over-represented in patients with the Lewy body variant of Alzheimer’s disease. Neurology 44(10): 1950–1951.PubMedCrossRefGoogle Scholar
  25. Gearing M, Mirra SS, Hedreen JC, Sumi SM, et al. (1995) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer’s disease. Neurology 45(3 Pt 1): 461–466.Google Scholar
  26. Gentleman SM, Williams B, Royston MC, Jagoe R, et al. (1992) Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer’s disease and senile dementia of the Lewy body type. Neurosci Lett 142(1): 9–12.PubMedCrossRefGoogle Scholar
  27. Gibb WR, Esiri MM, Lees AJ (1987) Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain 110(Pt 5): 1131–1153.PubMedCrossRefGoogle Scholar
  28. Gibb WR, Luthert PJ, Janota I, Lantos PL (1989) Cortical Lewy body dementia: clinical features and classification. J Neurol Neurosurg Psychiatry 52(2): 185–192.PubMedCrossRefGoogle Scholar
  29. Golbe LI (1993) The genetics of Parkinson’s disease. Rev Neurosci 4(1): 1–16.PubMedCrossRefGoogle Scholar
  30. Hainfellner JA, Pilz P, Lassmann H, Ladurner G, et al. (1995) Diffuse Lewy body disease as substrate of primary lateral sclerosis. J Neurol 242(2): 59–63.PubMedCrossRefGoogle Scholar
  31. Hansen LA, Masliah E, Terry RD, Mirra SS (1989) A neuropathological subset of Alzheimer’s disease with concomitant Lewy body disease and spongiform change. Acta Neuropathol (Berl) 78(2): 194–201.CrossRefGoogle Scholar
  32. Hansen L, Salmon D, Galasko D, Masliah E, et al. (1990) The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 40(1): 1–8.PubMedCrossRefGoogle Scholar
  33. Hansen LA, Masliah E, Quijada-Fawcett S, Rexin D (1991) Entorhinal neurofibrillary tangles in Alzheimer disease with Lewy bodies. Neurosci Lett 129(2): 269–272.PubMedCrossRefGoogle Scholar
  34. Hansen LA, Masliah E, Galasko D, Terry RD (1993) Plaque-only Alzheimer disease is usually the lewy body variant, and vice versa. J Neuropathol Exp Neurol 52(6): 648–654.PubMedCrossRefGoogle Scholar
  35. Hansen LA, Galasko D, Samuel W, Xia Y, et al. (1994) Apolipoprotein-E epsilon-4 is associated with increased neurofibrillary pathology in the Lewy body variant of Alzheimer’s disease. Neurosci Lett 182(1): 63–65.PubMedCrossRefGoogle Scholar
  36. Hardy J (1994) Lewy bodies in Alzheimer’s disease in which the primary lesion is a mutation in the amyloid precursor protein. Neurosci Lett 180 (2): 290–291.PubMedCrossRefGoogle Scholar
  37. Hardy J, Crook R, Prihar G, Roberts G, et al. (1994) Senile dementia of the Lewy body type has an apolipoprotein E epsilon 4 allele frequency intermediate between controls and Alzheimer’s disease. Neurosci Lett 182(1): 1–2.PubMedCrossRefGoogle Scholar
  38. Harrington CR, Louwagie J, Rossau R, Vanmechelen E, et al. (1994a) Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer’s disease. Am J Pathol 145(6): 1472–1484.Google Scholar
  39. Harrington CR, Perry RH, Perry EK, Hurt J, et al. (1994b) Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein. Dementia 5(5): 215–228.PubMedGoogle Scholar
  40. Hughes AJ, Daniel SE, Blankson S, Lees AJ (1993) A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 50(2): 140–148.PubMedCrossRefGoogle Scholar
  41. Ince P, Irving D, MacArthur F, Perry RH (1991) Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson’s disease and non-demented elderly control patients. J Neurol Sci 106(2): 142–152.PubMedCrossRefGoogle Scholar
  42. Jackson M, Lennox G, Balsitis M, Lowe J (1995) Lewy body dysphagia. J Neurol Neurosurg Psychiatry 58(6): 756–758.PubMedCrossRefGoogle Scholar
  43. Kim H, Gearing M, Mirra SS (1995) Ubiquitin-positive CA2/3 neurites in hippocampus coexist with cortical Lewy bodies. Neurology 45(9): 1768–1770.PubMedCrossRefGoogle Scholar
  44. Kosaka K (1990) Diffuse Lewy body disease in Japan. J Neurol 237(3): 197–204.PubMedCrossRefGoogle Scholar
  45. Kosaka K (1993) Dementia and neuropathology in Lewy body disease. Adv Neurol 60: 456–463.PubMedGoogle Scholar
  46. Kosaka K, Yoshimura M, Ikeda K, Budka H (1984) Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree — A new disease? Clin Neuropathol 3(5): 185–192.PubMedGoogle Scholar
  47. Kosaka K, Iseki E, Odawara T (1994) Cerebral type of Lewy body disease — a case report. Neuropathology 16: 72–75.Google Scholar
  48. Kulisevsky J, Marti MJ, Ferrer I, Tolosa E (1988) Meige syndrome: neuropathology of a case. Mov Disord 3(2): 170–175.PubMedCrossRefGoogle Scholar
  49. Lantos PL, Ovenstone IM, Johnson J, Clelland CA, et al. (1994) Lewy bodies in the brain of two members of a family with the 717 (Val to Ile) mutation of the amyloid precursor protein gene. Neurosci Lett 172(1–2): 77–79.PubMedCrossRefGoogle Scholar
  50. Lennox G (1992) Lewy body dementia. Baillières Clin Neurol 1(3): 653–676.PubMedGoogle Scholar
  51. Lennox G, Lowe J, Landon M, Byrne EJ, et al. (1989a) Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry. J Neurol Neurosurg Psychiatry 52(11): 1236–1247.PubMedCrossRefGoogle Scholar
  52. Lennox G, Lowe J, Morrell K, Landon M, et al. (1989b) Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease. J Neurol Neurosurg Psychiatry 52(1): 67–71.PubMedCrossRefGoogle Scholar
  53. Lippa CF, Smith TW, Swearer JM (1994) Alzheimer’s disease and Lewy body disease: a comparative clinicopathological study [published erratum appears in Ann Neurol (1994) 35(3):380]. Ann Neurol 35(1): 81–88.PubMedCrossRefGoogle Scholar
  54. Lippa CF, Smith TW, Saunders AM, Crook R, et al. (1995) Apolipoprotein E genotype and Lewy body disease. Neurology 45(1): 97–103.PubMedCrossRefGoogle Scholar
  55. Lowe J (1994) Lewy bodies. In: Calne D (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 51–69.Google Scholar
  56. Mark MH, Sage JI, Dickson DW, Heikkila RE, et al. (1994) Meige syndrome in the spectrum of Lewy body disease. Neurology 44(8): 1432–1436.PubMedCrossRefGoogle Scholar
  57. Mark M, Dickson D, Sage J, Duvoisin R (1996) The clinicopathologic spectrum of Lewy body disease. Adv Neurol 69: 315–318.PubMedGoogle Scholar
  58. McKeith IG, Perry RH, Fairbairn AF, Jabeen S, et al. (1992) Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med 22(4): 911–922.PubMedCrossRefGoogle Scholar
  59. McKeith IG, Fairbairn AF, Bothwell RA, Moore PB, et al. (1994) An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type. Neurology 44(5): 872–877.PubMedCrossRefGoogle Scholar
  60. Mirra SS, Heyman A, McKeel D, Sumi SM, et al. (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41(4): 479–486.Google Scholar
  61. Mori H, Yoshimura M, Tomonaga M, Yamanouchi H (1986) Progressive supranuclear palsy with Lewy bodies. Acta Neuropathol (Beri) 71(3–4): 344–346.CrossRefGoogle Scholar
  62. Olsson JE, Brunk U, Lindvall B, Eeg-Olofsson O (1992) Dopa-responsive dystonia with depigmentation of the substantia nigra and formation of Lewy bodies. J Neurol Sci 112(1–2): 90–95.PubMedCrossRefGoogle Scholar
  63. Pellise A, Roig C, BarraquerBordas L, Ferrer I (1996) Abnormal, ubiquitinated cortical neurites in patients with diffuse Lewy body disease. Neurosci Lett 206(2–3): 85–88.PubMedCrossRefGoogle Scholar
  64. Perry RH, Irving D, Blessed G, Fairbairn A, et al. (1990) Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 95(2): 119–139.Google Scholar
  65. Perry EK, Haroutunian V, Davis KL, Levy R, et al. (1994) Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer’s disease. Neuroreport 5(7): 747–749.PubMedCrossRefGoogle Scholar
  66. Pollanen MS, Dickson DW, Bergeron C (1993) Pathology and biology of the Lewy body. J Neuropathol Exp Neurol 52(3): 183–191.PubMedCrossRefGoogle Scholar
  67. Saitoh T, Xia Y, Chen X, Masliah E, et al. (1995) The CYP2D6B mutant allele is over represented in the Lewy body variant of Alzheimer’s disease. Ann Neurol 37(1): 110–112.PubMedCrossRefGoogle Scholar
  68. Samuel W, Galasko D, Masliah E, Hansen LA (1996) Neocortical Lewy body counts correlate with dementia in the Lewy body variant of Alzheimer’s disease. J Neuropathol Exp Neurol 55(1): 44–52.PubMedCrossRefGoogle Scholar
  69. Sima AA, Clark AW, Sternberger NA, Sternberger LA (1986) Lewy body dementia without Alzheimer changes. Can J Neurol Sci 13 [4 Suppl]: 490–497.PubMedGoogle Scholar
  70. St Clair D, Norman J, Perry R, Yates C, et al. (1994) Apolipoprotein E epsilon 4 allele frequency in patients with Lewy body dementia, Alzheimer’s disease and age matched controls. Neurosci Lett 176(1): 45–46.PubMedCrossRefGoogle Scholar
  71. Wakabayashi K, Honer WG, Masliah E (1994) Synapse alterations in the hippocampal- entorhinal formation in Alzheimer’s disease with and without Lewy body disease. Brain Res 667(1): 24–32.PubMedCrossRefGoogle Scholar
  72. Wu E, Lipton RB, Dickson DW (1992) Amyloid angiopathy in diffuse Lewy body disease. Neurology 42(11): 2131–2135.PubMedCrossRefGoogle Scholar
  73. Yoshimura N, Yoshimura I, Asada M, Hayashi S, et al. (1988) Juvenile Parkinson’s disease with widespread Lewy bodies in the brain. Acta Neuropathol (Berl) 77(2): 213–218.Google Scholar
  74. Zhan SS, Beyreuther K, Schmitt HP (1993) Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. Dementia 4(2): 66–74.PubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1997

Authors and Affiliations

  • J. Lowe
    • 1
  • D. Dickson
    • 2
  1. 1.Department of Clinical Laboratory Sciences, Division of PathologyUniversity of Nottingham Medical School, Queen’s Medical CentreNottinghamUK
  2. 2.Neuropathology, Albert Einstein College of MedicineNew YorkUSA

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