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Non-motor Subtypes of Early Parkinson Disease in the Parkinson's Progression Markers Initiative

S. Jain; S Young Park
WFN: San Diego, CA
Download Presentation: Jain-WFN-2013-PPMI-presentation.pdf
Regional North American Meeting of the World Federation of Neurology - Research Group on Neuroepidemiology

Title: Non-motor subtypes of Early Parkinson Disease in the Parkinson?s Progression Markers Initiative

Authors: Samay Jain MD MSc, Seo Young Park PhD

Objective: To explore whether subtypes of Parkinson disease (PD) may be defined by non-motor features in a cohort of recently diagnosed PD patients.

Background: Parkinson disease (PD) is a multi-system, multi-organ disease with varied clinical presentations and pathologic changes in the central nervous system and peripheral end-organs. The clinical period commences with a pre-motor phase characterized by varied non-motor features follow by motor signs that lead to diagnosis. As non-motor features predate motor signs, characterizing patterns of non-motor features in early PD my inform models of pathogenesis and disease surveillance.

Methods: The Parkinson?s Progression Markers Initiative is an observational cohort which currently contains 345 individuals with PD who at enrollment were: at least 30 years old; diagnosed within that last 2 years; and not treated for PD. Baseline assessments of motor, neurobehavioral, cognitive, autonomic, sleep and olfactory features were completed. K-means cluster analysis was performed using baseline non-motor characteristics. The number of clusters was determined by comparing the sum of squared error (SSE) distance between each member of a cluster and the cluster center in actual data versus 250 randomized versions. To plot clusters, principal components analyses were performed. Clusters were validated by ANOVA and Fischer?s exact test on variables not used for clustering.

Results: Four PD subtypes derived from non-motor features emerged (% of PD population): (1) Cognitive and Olfactory Impairment (17%) with the most impaired cognitive and olfactory function; (2) Younger onset, mildest non-motor features, slowest progression (32%); (3) Intermediate burden (38%); and (4) Non-cognitive, non-motor impairment with rapid progression (13%) with the most severe sleep, depressive and autonomic symptoms and highest prevalence of impulsive/compulsive features.

Conclusions: These preliminary results suggest PD subtypes defined by non-motor features exist early in the clinical period. Such patterns of non-motor features may be present prior to diagnostic motor signs in longitudinal cohorts with incident PD cases.