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

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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 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.

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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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Authors and Affiliations

  1. Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Thomas G. Beach, LihFen Lue, Lucia I. Sue, Jyothi Bachalakuri, Jonette Henry-Watson, Jeanne Sasse, Sarah Boyer, Scophil Shirohi, Reed Brooks, Holly A. Shill, Donald J. Connor, Marwan N. Sabbagh & Douglas G. Walker

  2. Mayo Clinic, Scottsdale, AZ, USA

    Charles H. Adler & John Caviness

  3. Barrow Neurological Institute, Phoenix, AZ, USA

    Jennifer Eschbacher

  4. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Charles L. White III

  5. Tokyo Institute of Psychiatry, Tokyo, Japan

    Haru Akiyama

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  1. Thomas G. Beach
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  2. Charles H. Adler
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  3. LihFen Lue
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  15. Holly A. Shill
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  16. Donald J. Connor
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  18. Douglas G. Walker
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the Arizona Parkinson’s Disease Consortium

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Correspondence to Thomas G. Beach.

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Beach, T.G., Adler, C.H., Lue, L. et al. Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 117, 613–634 (2009). https://doi.org/10.1007/s00401-009-0538-8

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  • DOI: https://doi.org/10.1007/s00401-009-0538-8

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