Objective: To assess the prognostic relevance of a data-driven PD subtyping system generated in the Longitudinal and Biomarker Studies in Parkinson’s disease study (LABS-PD) in terms of functional ability, quality of life and mortality

Background: Research on Parkinson’s disease heterogeneity and subtyping may inform prognosis by predicting clinical milestones. Prognostic relevance of clinically meaningful outcomes are desirable characteristics of a PD subtyping solution.  Previously defined PD subtypes’ prognostic value has been generally understudied.

Method: To identify PD subtypes, we conducted cluster analyses in the LABS-PD cohort with 461 PD patients enrolled in the randomized controlled trial CEP-1347 (PRECEPT) within two years of diagnosis, followed for at least five years. We determined the association of each subtype with change in the Schwab & England-Activities of Daily Living (SE-ADL) and Parkinson’s Disease Questionnaire -39(PDQ-39)  in a multiple linear regression model. We evaluated the association of each PD subtype with the hazard of death using a multivariable Cox proportional hazard regression model.

Results: We identified three subtypes: Tremor Predominant (n = 253), Motor complications (n = 183), and  Rapid progression (n = 25). A two-year score change of SE-ADL for the ‘Motor complications’ subtype ( -4.26, 95 CI: -6.60, -1.91) was worse compared to the ‘Tremor Predominant’ subtype (2.22, 95 CI: 0.43.-1.35). Only the ‘Motor complications’ subtype had a significant worsening of PDQ-39 score at two years. The adjusted death rate was higher for the ‘Motor Complications’ subtype compared with the ‘Tremor Predominant subtype (HR _{(time to death)}: 0.27, 95 CI:0.14, 0.52, with a significant interaction between age at subtype definition and subtype. In those >65 years of age, cumulative mortality was higher in the ‘Motor Complications’ subtype compared with ‘Tremor Predominant’ subtype.

Conclusion: PD subtypes generated in LABS-PD have some prognostic value for short-term functional ability and long-term survival. Membership to the “Tremor Predominant” subtype at 5 years after PD diagnosis was associated with preserved functional ability and longer survival compared to the “Motor Complications” subtype, particularly for those >65 years. Future work should focus on replicating the results in independent cohorts and validating clinical applicability at individual level.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prognostic-value-of-parkinsons-disease-subtypes-in-the-labs-pd-cohort-functional-ability-quality-of-life-and-mortality/