Parkinson's disease and related conditions

Abstract

Parkinson's disease (PD) is a common neurodegenerative condition, affecting 2–3% of individuals >65 years of age. It is characterized by a loss of dopaminergic neurons in the midbrain leading to a movement disorder encompassing bradykinesia, rest tremor, rigidity and postural stability. However patients also experience a range of non-motor symptoms, reflecting more widespread pathology in the peripheral and autonomic nervous systems as well as the brainstem and cortex. Some non-motor symptoms emerge years before motor problems. This prodromal stage of PD can represent the optimal time for intervention with future disease-modifying therapies. Other conditions can cause a similar syndrome of motor parkinsonism in combination with a range of non-motor features, leading to a degree of diagnostic uncertainty in early disease. However, they typically differ in their progression rate and response to treatment. Here, we discuss the natural history of PD and provide an update on its genetic and pathological basis before reviewing motor and non-motor symptomatology. We give an overview of related parkinsonian conditions and consider how they differ clinically from PD. We discuss currently available therapies and their complications, before reviewing new therapeutic developments and the need to target these precisely to particular diseases.