Parkinson's disease subtypes: literature review

Abstract

Parkinson's disease, like most neurodegenerative diseases, is clinically heterogeneous with a broad spectrum of motor and non-motor features. A number of studies have proposed and described subtypes of Parkinson's disease based on the characteristics of symptoms, which can be grouped. Subtyping makes possible optimization of the research of Parkinson's disease etiology, pathogenesis, prognosis and response to treatment, as subtypes should reflect the main pathomorphological and pathophysiological differences between patients. This review considered subtypes of Parkinson's disease identified so far, grouped common concepts and understanding of the relationship between subtypes and disease progression. A systematic review of articles in PubMed between 2009 and 2020 was performed using the following search terms: "Parkinson's disease subtypes", "Parkinson's disease phenotypes" for the time period of last 10 years (2009-2020). In this review article the most commonly identified subtypes of Parkinson's disease and their distinguishing features were discussed. As a result, 12 articles were identified, among them, 3 were data driven (cluster analysis). The classification based on the motor features of the disease, suggested by Jankovic et al. in 1990, remains the most popular to this day (tremor-dominant, akinetic-rigid or so called postural instability with gait impairment and mixed), but it is not very reliable, because patients tend to switch subtypes as the disease progresses. Cluster data analysis studies lack reproducibility and the method itself is too complex to be routinely used in clinical practice. In addition, it is yet not clear, if we are dealing with subtypes or just different stages of the disease. Thus, it was detected that the existing methods of Parkinson's disease subtyping by cluster data analysis and classification into motor subtypes cannot be considered fully correct and generally accepted, because the disease is not static and patients can change the subtype (especially in the early stages of the disease), although motor phenotypes utilization remains the most prevalent today. It is obvious, that subtyping requires inclusion of other features (genetic, molecular, neuroimaging) into analysis of the disease, in addition to clinical manifestations.