Subtypes of Parkinson's disease: state of the field and future directions

Purpose of review Previously, outstanding questions have been identified including the relationship of proposed subtypes to etiology, underlying biology, and prognosis. This situation presents an opportunity for major developments in the field. The review summarizes the progress made over the past 1-2 years. Recent findings The etiologic, physiological, and clinical differences between tremor dominant, postural instability gait disorder, and indeterminate phenotypes have been further explored, finding genetic influences, functional imaging and clinical differences. New cluster analyses suggest that nonmotor features are important aspects of Parkinson's disease subtypes, but there was little association found between tremor-dominant /postural instability gait disorder phenotype and nonmotor symptoms. In the cognitive realm, empirically derived subtypes of PD-MCI did not map well onto cognitive subtypes derived using a data-driven approach. In data-driven subtype research, important survival differences between subtypes were identified within the PROPARK database. It will be important to revisit PD-MCI classification to consider subtyping based upon data that relate cognitive phenotype to prognosis. Given the traction that traditional motor subtyping has had in the field it would be of value to consider how nonmotor symptom clusters can be used with or alongside the motor subtypes. Finally, incorporating subtypes into clinical trials remains a significant gap in Parkinson's disease research.