Refining the clinical diagnosis of Parkinson's disease.

Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical features and neuropathologic signatures can now be supplemented by in-vivo interrogation of genetic and biological substrates of disease, offering great opportunity for further refining the diagnosis of PD. In this mini-review, we discuss the historical perspectives which shaped our thinking surrounding the definition and diagnosis of PD. We highlight the clinical, genetic, pathologic and biologic diversity which underpins the condition, and proceed to discuss how recent developments in our ability to define biologic and pathologic substrates of disease might impact PD definition, diagnosis, individualised prognostication, and personalised clinical care. We argue that Parkinson's 'disease', as currently diagnosed in the clinic, is actually a syndrome. It is the outward manifestation of any array of potential dysfunctional biologic processes, neuropathological changes, and disease aetiologies, which culminate in common outward clinical features which we term PD; each person has their own unique disease, which we can now define with increasing precision. This is an exciting time in PD research and clinical care. Our ability to refine the clinical diagnosis of PD, incorporating in-vivo assessments of disease biology, neuropathology, and neurogenetics may well herald the era of biologically-based, precision medicine approaches PD management. With this however comes a number of challenges, including how to integrate these technologies into clinical practice in a way which is acceptable to patients, promotes meaningful changes to care, and minimises health economic impact.