Classification of Clinical Subtypes in Parkinson’s Disease Based on Phenotypic Variability in the Motor, Cognitive, and Psychiatric Domains (S19.002)

Objective: To identify clinical subtypes in Parkinson disease based on the pattern of motor, cognitive, and psychiatric symptoms, and to validate these subtypes using independent clinical and demographic features. Background: Parkinson disease (PD) is a heterogeneous disorder characterized by both motor and non-motor Typically, PD clinical subtypes focus on single domain phenotypes, such as motor subtypes of tremor versus non-tremor. Few studies, however, employ more comprehensive data-driven approaches to identify subtypes based on the presentation of symptoms across multiple domains of impairment. Methods: Data were obtained from 157 non-demented PD participants as part of a broad clinical assessment of motor, cognitive, and psychiatric symptoms. Latent class analysis delineated subtypes based on score patterns across the motor, cognitive, and psychiatric domains. Models were fit to individual manifestations from each domain controlling for sex, age, and education level: tremor, bradykinesia, rigidity, postural instability and gait difficulty (motor); attention, memory, language, visuospatial, and executive functions (cognitive); and depression and apathy (psychiatric). The relationship of latent classes with independent clinical and demographic variables was investigated with one-way ANOVAs and chi-square tests. Results: The latent class model identified three distinct clinical subtypes. One class (N=69) was characterized by predominant tremor with normal cognition and psychiatric function; the second class (N=70) was characterized by postural instability and gait difficulty, impaired cognition, and normal psychiatric function; and the third class (N=18) was characterized by elevated psychiatric symptoms with intermediate motor symptoms and normal cognition. Independent analyses indicated later age of onset and shorter disease duration for Class 1. Additionally, Class 3 contained the highest proportion of participants with cognitive impairment on the clinical dementia rating scale (CDR = 0.5), while Class 1 had the lowest. Conclusions: Study results emphasize the importance and contribution of non-motor symptoms to the overall pattern of phenotypic variability in PD. Disclosure: Dr. Campbell has nothing to disclose. Dr. Weigand has nothing to disclose. Dr. Lessov-Schlaggar has nothing to disclose. Dr. Perlmutter has received personal compensation for activities as a medical-legal consultant.