Advances in markers of prodromal Parkinson disease

Key Points

  • Diagnosis of Parkinson disease (PD) requires motor symptoms, but it is now clear that the typical motor signs are preceded by preclinical and prodromal phases of the disease

  • The utility of a marker of prodromal PD depends on the strength of evidence that it is a relevant marker, its specificity, its lead time, and the practicalities of assessment

  • Identification of reliable markers requires prospective studies; studies in high-risk populations are susceptible to selection bias and limited generalizability

  • The strongest marker of prodromal PD is rapid eye movement (REM) sleep behaviour disorder; other markers supported by strong evidence include subtle motor dysfunction, olfactory loss, autonomic dysfunction and affective disorders

  • Markers of prodromal PD have been combined to predict the probability of prodromal PD, most notably in the International Parkinson Disease Movement Disorders Society task force diagnostic guidelines

Abstract

Efforts to develop neuroprotective therapy for Parkinson disease (PD) are focusing on the early stages of disease, which offer the best opportunity to intervene. Early PD can be divided into preclinical, prodromal and clinical stages; in this Review, we focus on the prodromal stage and markers that can be used to identify prodromal PD. We consider the necessary properties of a marker, before providing an overview of the proven and potential markers of prodromal PD, including clinical nonmotor markers, clinical motor markers, neuroimaging markers and tissue biomarkers. Markers for which the ability to predict conversion to PD is supported by the strongest evidence include olfactory loss, REM sleep behaviour disorder and constipation. Markers with the highest diagnostic strength include REM sleep behaviour disorder, dopaminergic imaging and subtle motor parkinsonism. The lead time — the period between the appearance of a marker and conversion to PD — is highly variable between markers, ranging from 5 years for impaired motor performance to >20 years for autonomic symptoms. The cost of screening for these markers also varies dramatically: some require just questionnaires, whereas others require sophisticated scanning techniques. Finally, we summarize how prodromal and risk markers can be combined to estimate the probability that an individual has prodromal PD, with a focus on the International Parkinson Disease and Movement Disorders Society (MDS) Prodromal Parkinson Criteria.

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Figure 1: Phases and markers in Parkinson disease (PD).
Figure 2: Estimated lead times and diagnostic strengths of prodromal PD markers.

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Acknowledgements

R.B.P. has received grants from the Fonds de la Recherche en Sante Quebec, the Canadian Institute of Health Research, the Parkinson Society of Canada, the Weston-Garfield Foundation, the Michael J. Fox foundation, and the Webster Foundation. D.B. has received research grants from the European Union, the German Parkinson's Disease Association, the Michael J. Fox Foundation and Parkinson Fonds Deutschland.

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Correspondence to Ronald B. Postuma or Daniela Berg.

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R.B.P. has received funding for consultancy from Biotie, Biogen and Roche, and speaker fees from Novartis Canada and Teva Neurosciences. D.B. has received funds for consultancy and/or speaking from Lundbeck, Novartis, Teva and UCB, and research grants from Janssen Pharmaceuticals, Teva and UCB.

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Postuma, R., Berg, D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol 12, 622–634 (2016). https://doi.org/10.1038/nrneurol.2016.152

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