Challenges in the diagnosis of Parkinson's disease

Abstract

Parkinson's disease is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. An accurate diagnosis of Parkinson's disease remains challenging and the characterisation of the earliest stages of the disease is ongoing. Recent developments over the past 5 years include the validation of clinical diagnostic criteria, the introduction and testing of research criteria for prodromal Parkinson's disease, and the identification of genetic subtypes and a growing number of genetic variants associated with risk of Parkinson's disease. Substantial progress has been made in the development of diagnostic biomarkers, and genetic and imaging tests are already part of routine protocols in clinical practice, while novel tissue and fluid markers are under investigation. Parkinson's disease is evolving from a clinical to a biomarker-supported diagnostic entity, for which earlier identification is possible, different subtypes with diverse prognosis are recognised, and novel disease-modifying treatments are in development.

Conflict of interest statement

Declaration of interests ET reports honoraria for consultancy from TEVA, Bial, Prevail, Boehringer Ingelheim, Roche, and BIOGEN, and has received funding for research from the Spanish Network for Research on Neurodegenerative Disorders (CIBERNED)-Instituto Carlos III (ISCIII), and The Michael J Fox Foundation for Parkinson's Research. AG is supported by The Michael J Fox Foundation for Parkinson's Research; and reports honoraria from TEVA Pharma, and travel and meeting expenses from the International Movement Disorders Society. SWS reports funding from the intramural research programme of the National Institutes of Health (National Institute of Neurological Disorders and Stroke; project number, 1ZIANS003154). SWS serves on the Scientific Advisory Council of the Lewy Body Dementia Association and is an editorial board member for the Journal of Parkinson's Disease and JAMA Neurology. WP reports personal fees from AbbVie, Affiris, AstraZeneca, BIAL, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, Neuroderm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Teva, UCB, and Zambon. He reports consultancy and lecture fees in relation to clinical drug development programmes for Parkinson's disease and has received grant support from The Michael J Fox Foundation and the EU FP7 & Horizon 2020 programmes.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Figure.

The natural history of Parkinson’s disease and diagnostic challenges by disease stage RBD=REM sleep behavior disorder. Progressive supranuclear palsy-P=progressive supranuclear palsy with predominant parkinsonism. Multiple system atrophy-P=multiple system atrophy with predominant parkinsonism. The time of diagnosis is represented in the axis as time “0”. The timepoints on the left side of diagnosis represent the number of years before diagnosis, and the timepoints on the right represent the years after diagnosis. These periods of time are orientative. The dotted arrow indicates that the duration of the preclinical phase is unknown, unlike the prodromal phase, which can extend between 10 and 15 years.