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Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD

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Abstract

Background

The association of Lewy bodies (LBs) with olfactory dysfunction was investigated in community-dwelling elders without clinical Parkinson’s disease (PD) using the 12-item Brief Smell Identification Test (BSIT), a standard measure of odor identification.

Methods

280 participants in the Rush Memory and Aging Project completed the BSIT annually. Lewy bodies were detected in 13 brain regions by immunohistochemistry and were assigned to the Braak PD stages 1–6.

Results

Of the 280 participants, 101 (36.1%) had LBs which were maximal in the olfactory bulb and tract (85.1%) and least in Heschl’s cortex (21.8%). Due to the small number of cases in Braak PD stages 2, 3 and 5, the distribution of LBs in the 6 Braak PD stages was contracted into 3 main LB stages: (1) LBs in olfactory bulbs and dorsal motor nucleus of vagus, (2) further extension of LBs to limbic and other brainstem regions and (3) additional extension of LBs to neocortical areas. MMSE, global cognition and odor test scores were lower and frequency of dementia was higher at the time of the last valid BSIT, in cases with LBs as compared to those without LBs. Linear regression analyses showed that LBs were associated with impaired olfaction. However, on stratification of LBs into 3 stages, only the stage 3 cases were independently associated with impaired olfaction.

Conclusion

Although LB pathology was detected in olfactory bulbs in the early stage of LB progression (stage 1), the strongest association of LBs with olfactory dysfunction was observed in the late pathological stage (stage 3) when LBs extended to neocortical areas.

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Acknowledgements

We thank all the participants of the Rush Memory and Aging Project and the staff of Rush Alzheimer’s Disease Center including Er-Yun Chen and Alysha Hodges.

Funding

This work was supported by National Institutes of Health, National Institute on Aging (R01AG017917, R01NS078009, R01AG047976) and the Illinois Department of Public Health. The funding organizations had no role in the design or conduct of the study, collection, management, analysis or interpretation of the data; or preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Rush Alzheimer Disease Center, Suite 1000, Rush University Medical Center, 1750 W Harrison Street, Chicago, IL, 60612, USA

    Sukriti Nag, Lei Yu, Julie A. Schneider, David A. Bennett, Aron S. Buchman & Robert S. Wilson

  2. Department of Pathology (Neuropathology), Rush Alzheimer Disease Center and Rush University Medical Center, Chicago, IL, USA

    Sukriti Nag & Julie A. Schneider

  3. Neurological Sciences, Rush Alzheimer Disease Center and Rush University Medical Center, Chicago, IL, USA

    Lei Yu, Julie A. Schneider, David A. Bennett, Aron S. Buchman & Robert S. Wilson

  4. Psychiatry and Behavioral Sciences, Rush Alzheimer Disease Center and Rush University Medical Center, Chicago, IL, USA

    Robert S. Wilson

  5. Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Veronique G. VanderHorst

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  1. Sukriti Nag
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  2. Lei Yu
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Contributions

SN and RSW were involved in conception and design, analysis and interpretation of data. LY made substantial contributions to the design of the statistical analysis of the data. SN and VGV oversaw the acquisition of data and SN drafted the manuscript and revised it following review by all the authors. All the authors gave final approval of the version to be published. SN and RSW are accountable for all aspects of the work and will ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Sukriti Nag.

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The authors declare that they have no competing financial interests.

Ethics approval and consent to participate

Autopsied participants were from a longitudinal clinical–pathological study of aging and dementia, the Rush Memory and Aging Project. A signed, informed consent was obtained from each participant for an annual clinical evaluation and for brain donation. This study was approved by the Institutional Review Board of Rush University Medical Center and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Nag, S., Yu, L., VanderHorst, V.G. et al. Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD. J Neurol 266, 3108–3118 (2019). https://doi.org/10.1007/s00415-019-09540-5

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  • DOI: https://doi.org/10.1007/s00415-019-09540-5

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