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Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction

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the Arizona Parkinson’s Disease Consortium, Beach, Thomas G., Adler, Charles H., Lue, LihFen, Sue, Lucia I., Bachalakuri, Jyothi, Henry-Watson, Jonette, Sasse, Jeanne +11 more·2009·Acta Neuropathologica
DOI 10.1007/s00401-009-0538-8PMC PMC2757320
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Abstract

The two current major staging systems in use for Lewy body disorders fail to classify up to 50% of subjects. Both systems do not allow for large numbers of subjects who have Lewy-type alpha-synucleinopathy (LTS) confined to the olfactory bulb or who pass through a limbic-predominant pathway that at least initially bypasses the brainstem. The results of the current study, based on examination of a standard set of ten brain regions from 417 subjects stained immunohistochemically for alpha-synuclein, suggest a new staging system that, in this study, allows for the classification of all subjects with Lewy body disorders. The autopsied subjects included elderly subjects with Parkinson's disease, dementia with Lewy bodies, incidental Lewy body disease and Alzheimer's disease with Lewy bodies, as well as comparison groups without Lewy bodies. All subjects were classifiable into one of the following stages: I. Olfactory Bulb Only; IIa Brainstem Predominant; IIb Limbic Predominant; III Brainstem and Limbic; IV Neocortical. Progression of subjects through these stages was accompanied by a generally stepwise worsening in terms of striatal tyrosine hydroxylase concentration, substantia nigra pigmented neuron loss score, Mini Mental State Examination score and score on the Unified Parkinson's Disease Rating Scale Part 3. Additionally, there were significant correlations between these measures and LTS density scores. It is suggested that the proposed staging system would improve on its predecessors by allowing classification of a much greater proportion of cases.

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Authors
the Arizona Parkinson’s Disease Consortium, Beach, T. G., Adler, C. H., Lue, L., Sue, L. I., Bachalakuri, J., Henry-Watson, J., Sasse, J., Boyer, S., Shirohi, S., Brooks, R., Eschbacher, J., White, C. L., Akiyama, H., Caviness, J., Shill, H. A., Connor, D. J., Sabbagh, M. N., & Walker, D. G.
Affiliations
  • Banner Sun Health Research Institute (US)
  • Mayo Clinic (US)
  • Barrow Neurological Institute (US)
  • The University of Texas Southwestern Medical Center (US)
  • Tokyo Institute of Psychiatry (JP)
Corresponding author
Beach, Thomas G.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2009-04-28
Volume
117
Issue
6
Pages
613-634
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-009-0538-8
PMC
PMC2757320
OpenAlex
W1969541118
Cited by
698
References
4
Citations by year
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FWCI
18.35
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Society for the Promotion of Science (21591536)
  • National Institute on Aging (P30-AG-19610, P30AG019610)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
Lewy body disease, disease staging, alpha-synuclein, olfactory bulb, brainstem, nigrostriatal degeneration, cognitive impairment, motor impairment, Parkinson's disease, dementia with Lewy bodies, incidental Lewy body disease
MeSH terms
Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Brain, Cognition Disorders, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Male, Movement Disorders, Nerve Degeneration, Parkinson Disease, Severity of Illness Index, Neurodegenerative Diseases, Lewy Body Disease, alpha-Synuclein

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