LAUSR

BACKGROUND Research on Parkinson's disease (PD) heterogeneity may inform clinical prognosis. There is currently no fully validated PD subtype classification system. OBJECTIVES We aimed at assessing the prognostic relevance of a data-driven PD subtype classification system. METHODS To identify PD subtypes, we conducted cluster analyses in the Longitudinal and Biomarker Studies in Parkinson's Disease study (LABS-PD) cohort including 461 PD patients enrolled within 2 years of diagnosis and followed for at least 5 years. We determined the association of each PD subtype with the mean changes in the Schwab & England Activities of Daily Living (SE-ADL) and Parkinson's Disease Questionnaire-39 (PDQ-39). We evaluated the association of each PD subtype with the death rate and time to death, after mortality ascertainment using the National Death Index database and review of records at study sites. RESULTS We identified three subtypes: Tremor Predominant, Motor Complications, and Rapid Progression. Over 2 years, the change of SE-ADL score for the "Motor Complications" subtype (-4.26, 95% CI: -6.60, -1.91) was worse compared to the "Tremor Predominant" subtype (0.43, 95% CI: -1.35, 2.22). The adjusted death rate was lower for the "Tremor Predominant" subtype compared to the "Motor Complications" subtype (HR [time to death]: 0.27, 95% CI: 0.14, 0.52). CONCLUSIONS PD subtypes generated in LABS-PD cohort have prognostic value, for short-term functional ability and long-term survival. Membership in the "Tremor Predominant" subtype 5 years after PD diagnosis was associated with preserved functional ability and longer survival compared to the "Motor Complications" subtype.