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Non-motor features of Parkinson disease

Nature Reviews Neuroscience volume 18, pages 435–450 (2017)Cite this article

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An Erratum to this article was published on 13 July 2017

Key Points

  • Non-motor symptoms are common in Parkinson disease (PD) and can appear before motor features and progress in both severity and diversity as the disease evolves.

  • Both dopaminergic and non-dopaminergic pathology underlie the non-motor features, and this pathology involves the central and autonomic nervous systems.

  • There is no accurate toxin-induced or genetic animal model of PD pathology, and models for the study of non-motor features are limited.

  • A combination of non-motor features with additional biochemical and/or imaging studies may provide a means to identify prodromal, pre-motor PD.

  • There is accumulating evidence that α-synuclein pathology may spread along neuronal pathways and that this may originate in the gastrointestinal tract autonomic plexi.

  • Therapies designed to slow the course of PD will need to address pathology in non-dopaminergic neurons so as to influence non-motor, as well as motor, features of the disease.

Abstract

Many of the motor symptoms of Parkinson disease (PD) can be preceded, sometimes for several years, by non-motor symptoms that include hyposmia, sleep disorders, depression and constipation. These non-motor features appear across the spectrum of patients with PD, including individuals with genetic causes of PD. The neuroanatomical and neuropharmacological bases of non-motor abnormalities in PD remain largely undefined. Here, we discuss recent advances that have helped to establish the presence, severity and effect on the quality of life of non-motor symptoms in PD, and the neuroanatomical and neuropharmacological mechanisms involved. We also discuss the potential for the non-motor features to define a prodrome that may enable the early diagnosis of PD.

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Figure 1: Time courses of the onset of the motor and non-motor features of Parkinson disease.
Figure 2: Potential non-motor features in Parkinson disease.
Figure 3: Lewy bodies in Parkinson disease.
Figure 4: Schema representing the hypothesis of pathology spread via the intestine in Parkinson disease.

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Acknowledgements

A.H.V.S. is supported by a Medical Research Council (MRC) Centre of Excellence in Neurodegeneration grant (MR/L501499/1), a MRC Experimental Medicine programme award (MR/M006646/1) and a grant from Parkinson's UK (G-1403). A.H.V.S. is also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre award to University College London Hospitals.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, University College London (UCL) Institute of Neurology, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK

    Anthony H.V. Schapira

  2. National Parkinson Foundation International Centre of Excellence, King's College Hospital, King's College London, Camberwell Road, London, SE5 9RS, UK

    K. Ray Chaudhuri

  3. Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, Newcomen Street, London, SE1 1UL, UK

    Peter Jenner

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  1. Anthony H.V. Schapira
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  2. K. Ray Chaudhuri
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Correspondence to Anthony H.V. Schapira.

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PowerPoint slides

Glossary

Bradykinesia

Abnormal slowness of movement.

Rigidity

Stiffness and increased tone of muscles.

Levodopa

Orally active dopamine precursor.

Wearing off periods

Re-emergence of dopamine deficiency-related symptoms (for example, stiffness, slowness or tremor).

Off periods

Similar to 'wearing off' but more severe in terms of symptom severity.

On periods

Periods of effective dopamine replacement with restored motor function.

Hyposmia

Reduction in the ability to detect odours.

Rotenone

A mitochondrial complex I inhibitor and common pesticide.

α-Synuclein

A protein that aggregates and forms the major constituent of Lewy bodies in neurons. Mutations in the gene encoding α-synuclein and overexpression of this protein are causes of familial Parkinson disease.

Anosmia

Loss of the sense of smell.

Lewy bodies

Abnormal aggregates of proteinaceous material within neuronal cell bodies, the major constituent of which is α-synuclein.

Lewy neurites

Abnormal aggregates of proteinaceous material within axons, the major constituent of which is α-synuclein.

Incidental Lewy body disease

(ILBD). The presence on pathological examination of Lewy body deposition, but without symptoms of Parkinson disease during life.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

(MPTP). A mitochondrial complex I inhibitor that can cause dopaminergic neuron death and induce parkinsonism in humans.

Paraesthesia

Positive sensory phenomena (for example, pins and needles).

Parkin

A protein that is involved in mitophagy.

Endogenous depression

Depressive symptoms that are not associated with triggers such as bereavement.

Sleep attacks

Sudden onset of sleep.

Akathisia

Motor restlessness.

Nocturia

The need to pass urine during the night.

Micturition

The process of passing urine.

Detrusor

A muscle that controls bladder function.

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Schapira, A., Chaudhuri, K. & Jenner, P. Non-motor features of Parkinson disease. Nat Rev Neurosci 18, 435–450 (2017). https://doi.org/10.1038/nrn.2017.62

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