Unified Staging System for Lewy Body Disorders: Correlation with Nigrostriatal Degeneration, Cognitive Impairment and Motor Dysfunction

By T. Beach, C. Adler, L. Lue, L. Sue, Jyothi Bachalakuri, Jonette Henry-Watson, J. Sasse, Sarah E. Boyer, Scophil Shirohi, Reed G Brooks and 8 more. Acta Neuropathologica, 2009

658 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Complementary and alternative medicine, Neurology

View Paper: https://www.semanticscholar.org/paper/bf9fd1333d45a1d92c614fe54b813db85baef1bc

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Citations in the corpus

Parkinson's disease and parkinsonism: neuropathology. (2012, background): “Some elderly individuals have Lewy bodies confined to the olfactory bulb (Fujishiro et al. 2008a; Beach et al. 2009) or the amygdala, the latter particularly true if associated with concurrent Alzheimer type pathology (Uchikado et al. 2006).”
Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study. (2020, background): “It seems probable that the first a-synuclein pathology arises in the amygdala or sometimes enters via the olfactory route, since post-mortem studies show that the amygdala and olfactory bulb are the two most common sites of ‘single-location’ a-synuclein pathology in incidental Lewy body disease (Par”
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease (2012, neutral): “Refinements of these criteria have been proposed [53,106].”
National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2011, neutral): “For cases with incomplete clinical history, we note that ‘‘Neocortical LBD’’ is correlated with greater likelihood of cognitive impairment [1, 11–13, 22, 31–33, 38, 46, 49, 52].”
Parkinson Disease Epidemiology, Pathology, Genetics and Pathophysiology (2019, result): “Indeed, some subsequent reports indicate that the anatomical pattern of Lewy pathology in some people clinically diagnosed with PD is not consistent with the Braak staging(62).”
Pathology of Neurodegenerative Diseases. (2017, background): “PD may have initial a-synuclein aggregates in the brainstem, or even within the peripheral autonomic nervous system, whereas initial a-synuclein aggregates in AD and DLB may be in olfactory and limbic areas (Uchikado et al. 2006b; Beach et al. 2009).”
Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction (2023, background): “While α-syn-related damage to mitochondrial activity is a common mechanism for virtually all cell body types, α-syn aggregates are not found randomly in the central nervous system (CNS) of PD patients [51], implying an increased susceptibility of specific brain areas to LB formation.”
Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders (2010, positive): “A sensitive immunohistochemical method for phosphorylated a-synuclein [8, 10] Electronic supplementary material The online version of this article (doi:10.”
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014, background): “…et al., 2002; Guillozet et al., 2003; Bennett et al., 2004; Kraybill et al., 2005; Holtzer et al., 2006; Markesbery et al., 2006; Koepsell et al., 2008; Whitwell et al., 2008; Beach et al., 2009; Brayne et al., 2009; Giannakopoulos et al., 2009; Sabbagh et al., 2010; Robinson et al., 2011).”
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012, neutral): “Numerous CPC studies have assessed the association between NFTs and cognitive status (38, 98, 154, 158, 162, 185, 188, 189, 191, 223 Y 232, 235 Y 240, 244, 250 Y 252, 258, 261, 264, 287 Y 296).”