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The psychosis spectrum in Parkinson disease

Key Points

  • Parkinson disease (PD) psychosis refers to a spectrum of illusions, hallucinations and delusions that occur throughout the disease course

  • Evolving literature highlights the importance of recognizing and treating PD psychosis, and understanding its role as a clinical biomarker of disease stage, distribution and future progression

  • Current evidence points to PD psychosis as a set of symptoms with distinct pathophysiological mechanisms, as opposed to a single pathophysiological symptom with a spectrum of severity

  • The relationship between neuropathology in PD psychosis and in vivo measures of reduced metabolism, functional MRI alterations and cortical volume loss remains unclear

  • Further studies are needed to explore the role of PD medication in unmasking psychosis symptoms, why psychosis symptoms predict worse cognitive outcome, comparisons of psychosis symptoms and mechanisms in different clinical conditions, and development of novel treatments

Abstract

In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors — for example, autonomic dysfunction — that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.

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Figure 1: Regions of cortical atrophy in PD psychosis.

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Acknowledgements

The authors thank Dr Michael Haworth for help in preparing the final manuscript, Dr Rowena Carter for help preparing Figure 1, and the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre and Dementia Unit and NIHR Programme Grants for Applied Research (SHAPED RP-PG-0610-10100) for supporting their involvement in this work. K.R.C. acknowledges support from the European Union, Parkinson's UK, the NIHR and the Parkinson's Disease Non Motor group. D.A. is a Royal Society Wolfson Research Merit Award Holder and thanks the Wolfson Foundation and the Royal Society for their support. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.

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Correspondence to Dominic H. ffytche.

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K.R.C. has consulted and served on advisory boards for Britannia, AbbVie, Neuronova, Mundipharma and UCB, and has also served on advisory boards for Synapsus and Medtronic. He has received honoraria from Boehringer Ingelheim, GlaxoSmithKline, AbbVie, Britannia, UCB, Mundipharma, Otsuka and Zambon, and grants from Boehringer Ingelheim, GlaxoSmithKline, Britannia, AbbVie, UCB and Neuronova. He holds intellectual property rights for the KPP scale and the PDSS, and receives royalties for the books Non-Motor Symptoms of Parkinson's Disease and Fastfacts: Parkinson's Disease. C.B. declares grants and personal fees from Lundbeck and Acadia, and personal fees from Roche, Orion, GlaxoSmithKline, Otusaka, Heptares and Lilly. D.A. has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and serves as a paid consultant for H. Lundbeck and Axovant. The other authors declare no competing interests.

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ffytche, D., Creese, B., Politis, M. et al. The psychosis spectrum in Parkinson disease. Nat Rev Neurol 13, 81–95 (2017). https://doi.org/10.1038/nrneurol.2016.200

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