Document Type

Article

Publication Date

9-2025

Keywords

dysarthria, dysphagia, genotypes, Parkinson's disease, phenotypes

Abstract

Objectives The objective of this study was to examine baseline and longitudinal differences of self-reported dysarthria and dysphagia in the most common genetic subtypes of Parkinson's disease (PD) using the Parkinson's Progression Marker Initiative (PPMI) dataset. Methods This was a retrospective, longitudinal study utilizing data from the PPMI dataset. Dysarthria- and dysphagia-specific questions from the Unified Parkinson's Disease Rating Scale (UPDRS) and Scales of Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT) were extracted for people with Parkinson's disease (PwPD) with leucine-rich repeat kinase 2 gene (LRRK2), GBA, and SNCA genotypes across up to five research visits. Relevant patient (age, sex, etc.) and disease (severity, phenotype, medication, etc.) data were extracted along with scores from the Montreal Cognitive Assessment (MoCA). Linear mixed models (LMMs) were used to analyse longitudinal data between genotypes, as well as to examine the interaction effects between genotypes and tremor dominant (TD) or postural instability/gait determinant (PIGD) phenotypes. Results A total of 211 PwPD met inclusion criteria at their baseline visit (LRRK2 n = 115, GBA n = 68, SNCA n = 15). LMMs displayed significant differences in genotypes longitudinally, with significant differences between LRRK2, GBA, and SNCA genotypes at multiple time points in dysarthria and dysphagia self-reports. LRRK2-genotyped participants routinely self-reported lower dysarthria (p < 0.001) and dysphagia severity for UPDRS (p < 0.001) and SCOPA-AUT (p = 0.007) questions. SNCA-genotyped participants self-reported the most severe dysarthria (p = 0.002) and dysphagia symptoms for UPDRS (p < 0.001) and SCOPA-AUT (p < 0.05) over time. There were no differences between genotypes at baseline, and no effects of motor phenotype at any time point. Conclusions This was the first study to examine longitudinally how genotypes in PD specifically impact self-reported dysarthria and dysphagia severity. Findings from our study suggest different genotypes of PD affect the degree of self-reporting dysarthria and dysphagia severity. Specifically, LRRK2 genotypes self-reported lower dysarthria and dysphagia severity, while SNCA genotypes self-reported the most severe dysarthria and dysphagia of this sample. Importantly, SNCA genotypes self-report a faster increase in severity over time compared to other genotypes. Substantially more work is needed to investigate the underlying physiological differences manifesting in dysarthria and dysphagia in different genotypes of PD.

Comments

Web of Science

Wiley

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