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Dementia with Lewy bodies — from scientific knowledge to clinical insights

Abstract

Dementia with Lewy bodies (DLB) is the underlying aetiology of 10–15% of all cases of dementia and as such is a clinically important diagnosis. In the past few years, substantial advances have been made in understanding the genetics and pathology of this condition. For example, research has expanded our knowledge of the proteinaceous inclusions that characterize the disease, has provided an appreciation of the role of disease-associated processes such as inflammation and has revealed an association between DLB and genes such as GBA. These insights might have broader relevance to other neurodegenerative conditions and are beginning to be translated into clinical trials. In this Review, we provide clinical insights for the basic scientist and a basic science foundation for the clinician. We discuss the history of the condition; the definition of DLB; the relationship between DLB and other neurodegenerative conditions; current understanding of the pathology, genetics, clinical presentation and diagnosis of DLB; options for treatment; and potential future directions for research.

Key points

  • Dementia with Lewy bodies (DLB) is a common cause of dementia.

  • Although DLB is hard to diagnose clinically, accurate diagnosis is important as it influences management.

  • Awareness of the disorder and investigative techniques such as 123I-ioflupane single-photon emission CT can enhance diagnostic accuracy.

  • Our understanding of the genetics and pathology of the condition is growing.

  • This increased understanding is feeding through to new therapeutic strategies and clinical trials.

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Fig. 1: Key events in the study of DLB.
Fig. 2: Consensus criteria for diagnosis of DLB.
Fig. 3: 3D structure of α-synuclein and formation of Lewy bodies.
Fig. 4: Characteristic imaging findings in AD and DLB.

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Acknowledgements

The authors thank A. L. Kantsadi (Department of Biochemistry, University of Oxford, UK), for representing α-synuclein monomer as a cartoon. The authors thank E. Mak (Department of Psychiatry, University of Cambridge, UK), for providing the MRI and 123I-ioflupane single-photon emission CT images in figure 4. The authors express appreciation and gratitude to the Windsor Unit and all associated staff for supporting dementia with Lewy bodies (DLB) studies. The authors thank the Cambridgeshire and Peterborough NHS Foundation Trust for funding N.A.A.’s Fellowship. J.T.O. is supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. J.T.O. has acted as a consultant for GE Healthcare, Avid/Lilly, TauRx, Axon, Axovant and Eisai and has received grant income from Avid/Lilly and Alliance Medical. B.R.U. was a principal investigator in the recent trial of intepirdine in DLB.

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Nature Reviews Neurology thanks G. Halliday, L. Bonanni and E. Londos for their contribution to the peer review of this work.

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Correspondence to Benjamin R. Underwood.

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Related links

Lewy Body Dementia Association: https://www.lbda.org

International Psychogeriatric Association: http://www.ipa-online.org

Lewy Body Society: https://www.lewybody.org

Alzheimer’s Research UK: https://www.alzheimersresearchuk.org

Alzheimer’s Society: https://www.alzheimers.org.uk

Windsor Research Unit — NIHR: http://www.cpft.nhs.uk/RandD/windsor-research-unit-2.htm

The Michael J. Fox Foundation for Parkinson’s Research: http://www.michaeljfox.org

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Arnaoutoglou, N.A., O’Brien, J.T. & Underwood, B.R. Dementia with Lewy bodies — from scientific knowledge to clinical insights. Nat Rev Neurol 15, 103–112 (2019). https://doi.org/10.1038/s41582-018-0107-7

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