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Acta Neuropathologica

, Volume 117, Issue 6, pp 613–634 | Cite as

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

  • Thomas G. Beach
  • Charles H. Adler
  • LihFen Lue
  • Lucia I. Sue
  • Jyothi Bachalakuri
  • Jonette Henry-Watson
  • Jeanne Sasse
  • Sarah Boyer
  • Scophil Shirohi
  • Reed Brooks
  • Jennifer Eschbacher
  • Charles L. WhiteIII
  • Haru Akiyama
  • John Caviness
  • Holly A. Shill
  • Donald J. Connor
  • Marwan N. Sabbagh
  • Douglas G. Walker
  • the Arizona Parkinson’s Disease Consortium
Original Paper

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 α-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 α-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.

Keywords

Parkinson’s disease Parkinsonism Dementia with Lewy bodies Alzheimer’s disease Incidental Lewy bodies α-synuclein Olfactory bulb Amgydala Limbic Brainstem Neocortex 

Notes

Acknowledgments

This research is supported by grants to the Sun Health Research Institute Brain Donation Program and the Arizona Parkinson’s Disease Consortium by the Michael J. Fox Foundation for Parkinson’s Research (The Prescott Family Initiative), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901) and the National Institute on Aging (P30 AG19610).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Thomas G. Beach
    • 1
  • Charles H. Adler
    • 2
  • LihFen Lue
    • 1
  • Lucia I. Sue
    • 1
  • Jyothi Bachalakuri
    • 1
  • Jonette Henry-Watson
    • 1
  • Jeanne Sasse
    • 1
  • Sarah Boyer
    • 1
  • Scophil Shirohi
    • 1
  • Reed Brooks
    • 1
  • Jennifer Eschbacher
    • 3
  • Charles L. WhiteIII
    • 4
  • Haru Akiyama
    • 5
  • John Caviness
    • 2
  • Holly A. Shill
    • 1
  • Donald J. Connor
    • 1
  • Marwan N. Sabbagh
    • 1
  • Douglas G. Walker
    • 1
  • the Arizona Parkinson’s Disease Consortium
  1. 1.Sun Health Research InstituteSun CityUSA
  2. 2.Mayo ClinicScottsdaleUSA
  3. 3.Barrow Neurological InstitutePhoenixUSA
  4. 4.University of Texas Southwestern Medical CenterDallasUSA
  5. 5.Tokyo Institute of PsychiatryTokyoJapan

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