Parkinson's disease.

Parkinson's disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson's disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3-5% of Parkinson's disease is explained by genetic causes linked to known Parkinson's disease genes, thus representing monogenic Parkinson's disease, whereas 90 genetic risk variants collectively explain 16-36% of the heritable risk of non-monogenic Parkinson's disease. Additional causal associations include having a relative with Parkinson's disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson's disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson's disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson's disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson's disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson's disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson's disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson's disease can be optimised.

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Declaration of interests BRB serves as the coeditor in chief for the Journal of Parkinson's Disease, serves on the editorial board of Practical Neurology and Digital Biomarkers, has received fees from serving on the scientific advisory board for Biogen and UCB (paid to the institute), has received fees for speaking at conferences from AbbVie, Biogen, UCB, Zambon, Roche, GE Healthcare, and Bial (paid to the institute), and has received research support from the Netherlands Organization for Health Research and Development, Michael J Fox Foundation, UCB, AbbVie, Stichting Parkinson Fonds, Hersenstichting Nederland, Parkinson's Foundation, Verily Life Sciences, Horizon 2020, Topsector Life Sciences and Health, and the Parkinson Vereniging, outside the submitted work. BRB does not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of the topics in this paper. MSO serves as a consultant for the Parkinson's Foundation, and has received research grants from US National Institutes of Health (NIH), Parkinson's Foundation, the Michael J Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MSO's DBS research is supported by NIH R01NR014852 and R01NS096008. MSO is the principal investigator of the NIH R25NS108939 Training Grant. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford, and Cambridge (movement disorders books). MSO is an associate editor for JAMA Neurology and for New England Journal of Medicine Journal Watch Neurology. MSO has participated in continuous medical education and educational activities on movement disorders funded by the Academy for Healthcare Learning, PeerView, Prime, QuantiaMD, WebMD and Medscape, Medicus, MedNet, Einstein, MedNet, Henry Stewart, American Academy of Neurology, Movement Disorders Society, and by Vanderbilt University. The institution (not MSO) receives grants from Medtronic, AbbVie, Boston Scientific, Abbottv, and Allergan and the principal investigator has no financial interest in these grants. MSO has participated as a site principal investigator, or coinvestigator, or both for several NIH, foundation, and industry funded trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. MSO does not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of the topics in this paper. CK is deputy editor of Movement Disorders and associate editor of Annals of Neurology. CK serves as a medical adviser to Centogene for genetic testing reports in the fields of movement disorders and dementia, excluding Parkinson's disease and does not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of the topics in this paper.