Speech difficulties in early de novo patients with Parkinson's disease

Introduction: Speech difficulties are a common debilitating feature of Parkinson's disease and we aimed to investigate whether speech difficulties are associated with striatal dopaminergic deficits and faster disease progression. Methods: Using the Parkinson's Progression Markers Initiative database, 143 early de novo Parkinson's disease patients with speech difficulties were identified and matched 1:1 with 143 Parkinson's disease patients without speech difficulties for age, disease duration and motor symptom severity. We investigated differences in clinical features and striatal [I-123]FP-CIT single photon emission computed tomography (SPECT) uptake in Parkinson's disease patients with and without speech difficulties. Cox proportional hazards analysis was carried out to investigate whether speech difficulties were predictive of a faster motor progression and cognitive decline. Results: Speech difficulties were more common in patients with an akinetic-rigid motor phenotype compared to those with a tremor-dominant phenotype. Parkinson's disease patients with speech difficulties had lower resting tremor (P = 0.027), higher autonomic dysfunction (P = 0.034), increased daytime sleepiness (ESS; P = 0.048), and a higher prevalence of REM sleep behaviour disorder (RBD) symptoms (P = 0.007) compared to those without speech difficulties. Parkinson's disease patients with speech difficulties had significantly lower [I-123]FP-CIT uptake in the striatum (P < 0.001), caudate (P = 0.003) and putamen (P = 0.003) compared to those without speech difficulties. The presence of speech difficulties was a predictor of cognitive decline [Hazard Ratio (HR): 0.341, 95% Confidence Interval (CD: 0.153-0.759; Wald: 6.945; P = 0.008), whereas it had no influence on motor progression (HR: 0.885, 95% CI: 0.662-1.183; Wald: 0.680; P > 0.10). Conclusion: Speech difficulties are associated with greater autonomic dysfunction, sleep disturbances and striatal dopaminergic deficit, and can serve as a predictor of faster cognitive decline in early Parkinson's disease.