Parkinson's Disease Subtypes
Like many neurodegenerative disorders, Parkinson's disease (PD) is clinically highly heterogeneous. A number of studies have proposed and defined subtypes of PD based on clinical features that tend to cluster together. These subtypes present an opportunity to refine studies of aetiology, course and treatment responsiveness in PD, as clinical variability must represent underlying biological or pathophysiological differences between individuals. In this paper, we review what subtypes have been identified in PD and the validation they have undergone. We then discuss what the subtypes could tell us about the disease and how they have been incorporated into studies of aetiology, progression and treatment. Finally, with the knowledge that they have been incorporated very little into PD clinical research, we make recommendations for how subtypes should be used and make some practical recommendations to address this lack of knowledge translation.
Parkinson's disease (PD) is a remarkably variable condition, to the extent that 'Parkinson's diseases' has been proposed as a more appropriate term to describe the clinical entities. This variability has prompted a number of studies investigating the existence of PD subtypes, which divide PD patients into groups based on clinical or demographic features. Many different groupings or subtype classification systems have been proposed, which raises questions about which are most useful and their implications for future research. Despite extensive research efforts to subtype PD, and evidence that subtypes are associated with disease progression, subtypes have been integrated into very few clinical research studies. We argue that subtypes are only useful if they have an underlying relationship to aetiology, prognosis or treatment responsiveness. If they do, they can be useful tools to improve research methods and thus find a cure or better treatments, or help us to counsel patients or direct existing therapies. These opportunities can only be seized if subtypes are incorporated into clinical research studies. In this paper, we will discuss the purpose of subtyping, the current state of knowledge of PD subtypes and how subtypes can optimally be used in studies of aetiology, progression and treatment of PD.
Abstract and Introduction
Abstract
Like many neurodegenerative disorders, Parkinson's disease (PD) is clinically highly heterogeneous. A number of studies have proposed and defined subtypes of PD based on clinical features that tend to cluster together. These subtypes present an opportunity to refine studies of aetiology, course and treatment responsiveness in PD, as clinical variability must represent underlying biological or pathophysiological differences between individuals. In this paper, we review what subtypes have been identified in PD and the validation they have undergone. We then discuss what the subtypes could tell us about the disease and how they have been incorporated into studies of aetiology, progression and treatment. Finally, with the knowledge that they have been incorporated very little into PD clinical research, we make recommendations for how subtypes should be used and make some practical recommendations to address this lack of knowledge translation.
Introduction
Parkinson's disease (PD) is a remarkably variable condition, to the extent that 'Parkinson's diseases' has been proposed as a more appropriate term to describe the clinical entities. This variability has prompted a number of studies investigating the existence of PD subtypes, which divide PD patients into groups based on clinical or demographic features. Many different groupings or subtype classification systems have been proposed, which raises questions about which are most useful and their implications for future research. Despite extensive research efforts to subtype PD, and evidence that subtypes are associated with disease progression, subtypes have been integrated into very few clinical research studies. We argue that subtypes are only useful if they have an underlying relationship to aetiology, prognosis or treatment responsiveness. If they do, they can be useful tools to improve research methods and thus find a cure or better treatments, or help us to counsel patients or direct existing therapies. These opportunities can only be seized if subtypes are incorporated into clinical research studies. In this paper, we will discuss the purpose of subtyping, the current state of knowledge of PD subtypes and how subtypes can optimally be used in studies of aetiology, progression and treatment of PD.