Objective: To compare the relative incidence rates, at identical disease duration, of motor and nonmotor clinical milestones in the long-term disease course of Parkinson’s disease (PD) patients subgroups.

Background: Observational cross-sectional studies consistently indicate differences in PD patients’ subtypes with older patients experiencing a more rapid and severe disease course. However, information is missing regarding multi-domain nonmotor symptoms and evolution in a large population. 

Methods: We conducted an observational prospective incident cohort study and systematically assessed 9 outcomes encompassing multiple domains in all consecutive PD outpatients visiting our university hospital from 2003 to 2015. We recorded the date of first occurrence of motor fluctuations (MF), dyskinesia, postural instability, freezing of gait (FOG), nonmotor fluctuations (NMF), impulse control disorders (ICDs), hallucinations, dementia and postural hypotension as we were interested in time-to-event analysis of complications starting after diagnosis. Survival analysis for multiple failures was conducted using an extended multivariable marginal Cox regression model incorporating time-dependent covariates to determine cause-specific hazard for each outcome.

Results: A total of 1333 patients experienced 1815 disease related complications during the 12 years follow-up period. Younger age at diagnosis strongly determined the susceptibility to develop MF (HR 0.974 [0.963-0.984] per year increase), dyskinesias (0.974 [0.962-0.986]) and ICDs (HR 0.964 [0.948-0.980]), as did female gender for MF and dyskinesias, and male gender for ICDs, independently of the medication and disease course. At the opposite, older patients were more prone to develop postural instability (HR 1.058 [1.043-1.072]), FOG (1.034 [1.012-1.056]), hallucinations (HR 1.029 [1.009-1.049]), dementia (HR 1.100 [1.052-1.150]) and postural hypotension (HR 1.062 [1.040-1.085]). Bilateral onset was associated with higher relative incident rate in FOG (HR 2.14 [1.23-3.71]).

Conclusions: Specific clinical markers of the patients’ characteristics at onset, but also along disease course, predict PD-related disabling complications, dominated by age at diagnosis, sex, medication and occurrence of MF, dyskinesias, FOG and hallucinations. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cause-specific-hazard-of-motor-and-nonmotor-long-term-complications-of-idiopathic-parkinsons-disease-in-a-hospital-based-outpatient-clinic-incident-cohort-of-1333-patients/