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Abstract

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD).The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.
NEUROLOGY 1996;47: 1113-1124

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REFERENCES

1.
Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci 1970;11:205-242.
2.
McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939-944.
3.
Roman GC, Tatemich ITK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop. Neurology 1993;43:240-260.
4.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington DC: American Psychiatric Association, 1994.
5.
World Health Organisation. The ICD-10 classification of mental and behavioural disorders. Geneva: WHO, 1992.
6.
Kosaka K, Yoshimura M, Ikeda K, et al. Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree-a new disease? Clin Neuropathol 1984;3:185-192.
7.
Perry RH, Irving D, Blessed G, et al. Senile dementia of Lewy body type. A clinically and neuropathologically distinct type of Lewy body dementia in the elderly. J Neurol Sci 95:119-139.
8.
Lennox G, Lowe J, Morrell R, et al. Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease. J Neurol Neurosurg Psychiatry 1989;52:67-71.
9.
Hansen LA, Salmon D, Galasko D, et al. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology 1990;40:1-8.
10.
Dickson DW, Ruan D, Crystal H, et al. 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 1991;41:1402-1409.
11.
Kosaka K. Diffuse Lewy body disease in Japan. J Neurol 1990;237:197-204.
12.
Ince PG, Irving D, McArthur F, et al. 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 1991;106:142-152.
13.
Harrington CR, Wischik CM, Hurt J, et al. Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau proteins. Dementia 1994;5:215-228.
14.
Ditter SM, Mirra SS. Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients. Neurology 1987;37:754-760.
15.
Byrne EJ, Lennox G, Godwin Austen RB, et al. (Nottingham Group for the study of Neurodegenerative Disorders). Diagnostic criteria for dementia associated with cortical Lewy bodies. Dementia 1991;2:283-284.
16.
McKeith IG, Perry RH, Fairbairn AF, et al. Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med 1992;22:911-922.
17.
McKeith IG, Fairbairn AF, Perry RH, et al. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. B Med J 1992;305:673-678.
18.
Perry EK, Haroutunian V, Davis KL, et al. Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer's disease. Neuro Report 1994;5:747-749.
19.
Sahgal A, Galloway PH, McKeith IG, et al. A comparative study of attentional deficits in senile dementias of Alzheimer and Lewy body types. Dementia 1992;3:350-354.
20.
Salmon DP, Galasko D. Neuropsychological aspects of Lewy body dementia. In: Perry RH, McKeith IG, Perry EK, Dementia with Lewy bodies. New York: eds. Cambridge University Press, 1996:99-113.
21.
Byrne EJ, Lennox G, Lowe J, et al. Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry 1989;52:709-717.
22.
Klatka LA, Louis ED, Schiffer RB. Psychiatric features in diffuse Lewy body disease. Neurology 1996;47:1148-1152.
23.
Ballard C, Harrison RWS, Lowery K, McKeith IG. Noncognitive symptoms in Lewy body dementia. In: Perry RH, McKeith IG, Perry EK, eds. Dementia with Lewy bodies. New York: Cambridge University Press, 1996:67-84.
24.
McShane R, Gedling K, Reading M, et al. Prospective study of relations between cortical Lewy bodies, poor eyesight and hallucinations in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1995;59:185-188.
25.
McKeith IG, Fairbairn AF, Harrison RS. The management of the non-cognitive symptoms of Lewy body dementia. In: Perry RH, McKeith IG, Perry EK, eds. Dementia with Lewy bodies. New York: Cambridge University Press, 1996:381-396.
26.
Galasko D, Hansen LA. Lewy body disease. Curr Opin Neurol Neurosurg 1992;5:889-894.
27.
McKeith IG, Fairbairn AF, Bothwell RA, et al. An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type. Neurology 1994;44:872-877.
28.
Forstl H, Burns A, Levy R, et al. The Lewy-Body variant of Alzheimer's disease. Clinical and pathological findings. BJ Psychiatry 1993;162:385-392.
29.
McKeith IG. Lewy body disease. Curr Opin Psychiatry 1995;8:252-257.
30.
Galasko D, Saitoh T, Xia T, et al. The apolipoprotein E allele epsilon 4 is over-represented in patients with the Lewy body variant of Alzheimer's disease. Neurology 1995;44:1950-1951.
31.
Saitoh T, Xia Y, Chen X, et al. The CYP2D6B mutant allele is over-represented in the Lewy body variant of Alzheimer's disease. Ann Neurol 1995;37:110-112.
32.
Marder K, Maestre G, Cote L, et al. The apoliprotein epsilon 4 allele in Parkinson's disease with and without dementia. Neurology 1996;44:1330-1331.
33.
Armstrong M, Daly AK, Cholerton S, et al. Mutant debrisoquine hydroxylation genes in Parkinson's disease. Lancet 1992;339:1017-1018.
34.
Dale GE, Probst A, Luthert P, et al. Relationships between Lewy bodies and pale bodies in Parkinson's disease. Acta Neuropathol (Berl) 1992;83:525-529.
35.
Pollanen MS, Dickson DW, Bergeron C. Pathology and biology of the Lewy body. J Neuropathol Exp Neurol 1993;52:183-191.
36.
Braak H, Braak E, Yilmazer D, et al. Nigral and extranigral pathology in Parkinson's disease. J Neural Transm 1995;46(suppl):15-31.
37.
Kim H, Gearing M, Mirra SS. Ubiquitin positive CA2/3 neurites in hippocampus coexist with cortical Lewy bodies. Neurology 1995;45:1765-1770.
38.
Gai WP, Blessing WS, Blumberger PC. Ubiquitin-positive degenerating neurites in the brainstem in Parkinson's disease. Brain 1995;118:1447-1460.
39.
Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardisation of the neuropathologic assessment for Alzheimer's disease. Neurology 1991;41:479-486.
40.
Hansen LA, Masliah E, Galasko D, et al. Plaque only Alzheimer disease is usually the Lewy body variant, and vice versa. J Neuropathol Exp Neurol 1993;52:648-654.
41.
Braak H, Braak E. Neuropathological staging of Alzheimer related changes. Acta Neuropathol (Berl) 1991;82:239-259.
42.
Hansen LA, Masliah E, Terry RD, et al. A neuropathological subset of Alzheimer's disease with concomitant Lewy body disease and spongiform change. Acta Neuropathol 1989;78:194-201.
43.
Perry RH. Coronal map of Brodmann areas in the human brain. In: Roberts GW, Leigh PN, eds. Neuropsychiatric disorders. London: Wolfe, 1993:1-10.
44.
Kosaka K, Iseki E, Odawara T, et al. Cerebral type of Lewy body disease - a case report. Neuropathology 1994;16:72-75.
45.
Dickson DW, Davies P, Mayeux R, et al. Diffuse Lewy body disease. Acta Neuropathol 1987;75:8-15.
46.
Langlais PJ, Thal L, Hansen LA. Neurotransmitters in basal ganglia and cortex of Alzheimer's disease with and without Lewy bodies. Neurology 1993;43:1927-1934.
47.
Perry EK, Irving D, Kerwin JM, et al. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinctions from Alzheimer's disease. Alzheimer Dis Assoc Disord 1993;7:69-79.
48.
Perry EK, Marshall EF, Perry RH, et al. Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alzheimer Dis Assoc Disord 1990;4:87-95.
49.
Piggott M, Perry EK, Marshall EF, et al. Nigrostriatal dopaminergic activities in Lewy body dementia in relation to neuroleptic sensitivity: comparison with Parkinson's disease. Biol Psychiatry 1996 (in press).

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Published In

Neurology®
Volume 47Number 5November 1996
Pages: 1113-1124
PubMed: 8909416

Publication History

Published online: November 1, 1996
Published in print: November 1996

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Affiliations & Disclosures

S. Lovestone, MRC Psych
For the Consortium on Dementia with Lewy Bodies; *See pages 1122 and 1123 for the Consortium of Dementia with Lewy Bodies participants.
Presented at the Proceedings of the First International Workshop of the Consortium on DLB, Newcastle upon Tyne, UK, October 1995.
Supported by Parke Davis and Company, The French Foundation for Alzheimer Research, Janssen-Cilag Ltd, Sandoz Pharma Ltd, Bayer AG, F Hoffmann-La Roche AG, The Wellcome Trust, Eli Lilly and Company, Astra Arcus AB, Lederle Laboratories, Merck Sharp & Dohme Ltd, Institute for the Health of the Elderly, University of Newcastle upon Tyne, Medical Research Council (UK), Newcastle upon Tyne City Health NHS Trust, Royal Victoria Infirmary and Associated Hospitals NHS Trust.
Received April 1, 1996. Accepted in final form May 16, 1996.
Address correspondence and reprint requests to Dr McKeith, MD, BS, FRCPsych, Department of Old Age Psychiatry, Institute for the Health of the Elderly, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, U.K.

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