Longitudinal evolution of non-motor symptoms according to age at onset in early Parkinson's disease

Abstract

Objective: To investigate the longitudinal change of non-motor symptoms according to the age at onset in Parkinson's disease (PD).

Methods: This cohort study using the Parkinson's Progression Markers Initiative data included 405 patients with early PD. They were classified into late-onset (age at onset ≥ 70 years, n = 63), middle-onset (50 to 69 years, n = 268), and young-onset (<50 years, n = 74) groups. Non-motor symptoms were assessed with well-validated instruments covering neuropsychiatric, sleep-related, and autonomic symptoms yearly over 5 years of follow-up. Dopamine transporter imaging was also performed at baseline and the 1-, 2-, and 4-year follow-up visits.

Results: The late-onset group had a mean decrease of 0.35 more points per year in the Montreal Cognitive Assessment (MoCA) scores (p = 0.008) and increases of 0.32 more points in the 15-item Geriatric Depression Scale scores (p = 0.002) and 0.72 more points in the State-Trait Anxiety Inventory-state scores (p = 0.022) compared to the middle-onset group. The young-onset group had a mean decrease of 0.22 fewer points per year in the MoCA scores (p = 0.002) than the middle-onset group. The other non-motor progression did not differ among the groups. No significant differences were found between the late-onset, middle-onset, and young-onset groups in the changes of striatal DAT binding ratios.

Conclusion: Compared to middle-onset PD, late-onset PD showed a faster progression of cognitive impairment along with depression and anxiety, and young-onset PD showed a slower progression of cognitive impairment in the early phases of the disease. These differences do not appear to be associated with the longitudinal changes in striatal dopaminergic activities.

Keywords: Age at onset; Late-onset; Non-motor symptom; Parkinson's disease; Young-onset.