Impact of age at onset on symptom profiles, treatment characteristics and health-related quality of life in Parkinson's disease

Abstract

Parkinson's disease (PD) is typically considered an age-related disease, but the age at disease onset can vary by decades between patients. Aging and aging-associated diseases can affect the movement system independently of PD, and advanced age has previously been proposed to be associated with a more severe PD phenotype with accelerated progression. In this work, we investigated how interactions between PD progression and aging affect a wide range of outcomes related to PD motor and nonmotor symptoms as well as Health Related Quality of Life (HRQoL) and treatment characteristics. This population-based cohort study is based on 1436 PD patients from southern Sweden followed longitudinally for up to approximately 7.5 years from enrollment (3470 visits covering 2285 patient years, average follow-up time 1.7 years). Higher age at onset was generally associated with faster progression of motor symptoms, with a notable exception of dyskinesia and other levodopa-associated motor fluctuations that had less severe trajectories for patients with higher age at onset. Mixed results were observed for emergence of non-motor symptoms, while higher age at onset was generally associated with worse HRQoL trajectories. Accounting for these identified age-associated differences in disease progression could positively impact patient management and drug development efforts.

Figure 1

Baseline Spearman correlations between time variables (age at Parkinson’s Disease onset, age at Parkinson’s Disease diagnosis, age at baseline, years since Parkinson’s Disease onset, years since Parkinson’s Disease diagnosis), and respectively, symptom-based outcomes, Health related Quality of Life outcomes, and treatment outcomes.

Figure 2

Patient ages at study visits against patient age at onset. The black line represents age at onset, the orange line represents 7.5 years after onset, and the dark red line represents 15 years after onset.

Figure 3

Estimated 15-year mean trajectories of CISI-PD outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 2298 visits. Dotted line represents the estimated mean scores for patients with onset at the given age.

Figure 4

Estimated 15-year mean trajectories of staging and motor fluctuation outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 2307 visits (Hoehn & Yahr) and 2510 visits (motor fluctuation outcomes). Dotted line represents the estimated mean scores for patients with onset at the given age.

Figure 5

Estimated 15-year mean trajectories of Non-Motor Symptom Questionnaire outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 2758 visits. Dotted line represents the estimated mean scores for patients with onset at the given age.

Figure 6

Estimated 15-year mean trajectories of 8-item Parkinson’s Disease Questionnaire outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 2421 visits. Dotted line represents the estimated mean scores for patients with onset at the given age.

Figure 7

Estimated 15-year mean trajectories of EQ5D-3L outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 1800 visits. Dotted line represents the estimated mean scores for patients with onset at the given age.

Figure 8

Estimated 15-year mean trajectories of treatment outcomes from Parkinson’s disease onset at respectively 45, 55, 65, and 75 years of age. Trajectories estimated based on data from 205,463 prescriptions and pick-ups mapped to 3407 visits. Dotted line represents the estimated mean scores for patients with onset at the given age.