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Late-stage Parkinson disease

Nature Reviews Neurology volume 8, pages 435–442 (2012)Cite this article

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Abstract

The cardinal symptoms of Parkinson disease (PD) are asymmetrical bradykinesia, rigidity, resting tremor and postural instability. However, the presence and spectrum of, and disability caused by, nonmotor symptoms (NMS) are being increasingly recognized. NMS include dementia, psychosis, depression and apathy, and are a major source of disability in later stages of PD, in association with axial symptoms that are resistant to levodopa therapy. The model of clinical progression of PD should, therefore, incorporate NMS, instead of being restricted to motor signs and levodopa-induced motor complications. Patients with disabling motor complications are classified as having advanced PD, which has been thought to represent the ultimate stage of disease. However, deep brain stimulation to treat motor complications has dramatically changed this scenario, with implications for the definition of advanced-stage disease. As treatment improves and survival times increase, patients are increasingly progressing to a later phase of disease in which they are highly dependent on caregivers, and disability is dominated by motor symptoms and NMS that are resistant to levodopa. In this article, we review the changing landscape of the later stages of PD, and propose a definition of late-stage PD to designate patients who have progressed beyond the advanced stage.

Key Points

  • Advanced-stage Parkinson disease (PD) is widely accepted as a term to denote patients with motor complications, but many patients continue to progress to a less well-defined stage

  • Late stages of PD are of increasing clinical relevance owing to improved treatment and survival

  • Progression of PD is characterized by worsening disability owing to motor complications, nonmotor symptoms (NMS) and motor symptoms that are unresponsive to levodopa

  • Disability in late stages of PD is mostly associated with NMS such as dementia, psychosis and dysautonomia, and motor symptoms that are unresponsive to levodopa, such as dysarthria and falls

  • We propose a definition of late-stage PD in which patients are highly dependent on caregivers for activities of daily living, owing to motor symptoms or NMS that are resistant to levodopa

  • Future research should focus on the pathogenic mechanisms underlying late-stage PD, which could highlight therapeutic targets and potential end points for clinical trials

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Figure 1: Progression of PD in the post-levodopa and deep brain stimulation era.

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  1. Department of Neuroscience, Hospital Santa Maria, Neurological Clinical Research Unit, Instituto de Medicina Molecular, Avenida Professor Egas Moniz, Lisbon, 1649-028, Portugal

    Miguel Coelho & Joaquim J. Ferreira

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Correspondence to Joaquim J. Ferreira.

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Coelho, M., Ferreira, J. Late-stage Parkinson disease. Nat Rev Neurol 8, 435–442 (2012). https://doi.org/10.1038/nrneurol.2012.126

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