Objective: To evaluate the non-motor symptom(NMS), motor and cognition progression among the Parkinson Disease (PD) clusters derived from data-driven approach.

Background: Data-driven PD subtypes were found to have distinct prognosis. However, the previous longitudinal studies of data-driven PD subtypes did not provide detailed assessments of NMS and cognitive progression, which would be useful to holistically understand the disease course and guide PD management.

Method: In this 5-year prospective study, NMS scale(NMSS), Hospital Anxiety Depression Scale (HADS), Epworth sleepiness scale (ESS) were carried out anually to monitor NMS progression in PD patients from August 2014 to December 2021. H&Y staging scale, MDS-UPDRS part III motor score and postural instability gait difficulty (PIGD) score were assessed annually to evaluate disease severity and motor progression. Five cognitive standardized scores were used to assess detailed cognitive progression. Linear mixed model with random intercept effect was performed to assess the annual progression rates of the longitudinal outcomes.

Results: Two hundred and six early PD patients, consisting of 43 patients in cluster A, 98 patients in cluster B and 65 subjects in cluster C were followed up in this 5-year longitudinal study. Cluster A (severe subtype in motor, NMS and cognition) had significantly faster progression slope in NMSS total score (p<0.01), NMSS Domain 3 (mood/apathy) score (p<0.01), NMSS Domain 4 (perceptual problems ) score (p<.0001), HADS Anxiety Total score (p=0.02) than the other two clusters. Cluster A also progressed significantly in PIGD score (p=0.01). For cognitive outcomes, cluster A deteriorated significantly in visuospatial domain (p=0.0002) while cluster C (mild subtype and young age of onset) deteriorated significantly faster in executive domain (p=0.02) compared to the other two clusters.

Conclusion: The three PD clusters demonstrated different progression patterns. The severe cluster had significantly faster progression, particularly in mood and perceptual NMS domains, visuospatial cognitive performances and postural instability gait scores. Our findings will be helpful for clinicians to stratify and pre-emptively manage PD patients in different subtypes by developing intervention strategies to counter the progression of these domains.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-progression-of-data-driven-subtypes-of-parkinson-disease-pd-5-year-longitudinal-study-from-the-early-parkinsons-disease-longitudinal-singapore-pals-cohort/