Data-Driven Subtyping of Parkinson's Disease Using Longitudinal Clinical Records: A Cohort Study

Parkinson's disease (PD) is associated with diverse clinical manifestations including motor and non-motor signs and symptoms, and emerging biomarkers. We aimed to reveal the heterogeneity of PD to define subtypes and their progression rates using an automated deep learning algorithm on the top of longitudinal clinical records. This study utilizes the data collected from the Parkinson's Progression Markers Initiative (PPMI), which is a longitudinal cohort study of patients with newly diagnosed Parkinson's disease. Clinical information including motor and non-motor assessments, biospecimen examinations, and neuroimaging results were used for identification of PD subtypes. A deep learning algorithm, Long-Short Term Memory (LSTM), was used to represent each patient as a multi-dimensional time series for subtype identification. Both visualization and statistical analysis were performed for analyzing the obtained PD subtypes. As a result, 466 patients with idiopathic PD were investigated and three subtypes were identified. Subtype I (Mild Baseline, Moderate Motor Progression) is comprised of 43.1% of the participants, with average age 58.79 ± 9.53 years, and was characterized by moderate functional decay in motor ability but stable cognitive ability. Subtype II (Moderate Baseline, Mild Progression) is comprised of 22.9% of the participants, with average age 61.93 ± 6.56 years, and was characterized by mild functional decay in both motor and non-motor symptoms. Subtype III (Severe Baseline, Rapid Progression) is comprised 33.9% of the patients, with average age 65.32 ± 8.86 years, and was characterized by rapid progression of both motor and non-motor symptoms. These subtypes suggest that when comprehensive clinical and biomarker data are incorporated into a deep learning algorithm, the disease progression rates do not necessarily associate with baseline severities, and the progression rate of non-motor symptoms is not necessarily correlated with the progression rate of motor symptoms.