Neuropsychiatric Burden Is a Predictor of Early Freezing and Motor Progression in Drug-Naïve Parkinson's Disease

J Parkinsons Dis. 2021;11(4):1947-1956. doi: 10.3233/JPD-212660.

Abstract

Background: Neuropsychiatric symptoms (NPS) are the most common non-motor symptom in Parkinson's disease (PD).

Objective: To investigate the association between the burden of NPS and motor prognosis in patients with PD.

Methods: We enrolled 329 drug-naïve patients with PD, who was non-demented and followed-up≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging and neuropsychiatric inventory (NPI) scores. We performed a survival analysis and a linear mixed model analysis to assess longitudinal motor outcomes according to the NPI total score.

Results: The Kaplan-Meier analysis showed no difference in the development of levodopa-induced dyskinesia and wearing-off according to the NPI total score. However, higher burden of NPI total score was associated with earlier freezing of gait (FOG) development in the time-dependent Cox regression models after adjusting for age at symptom onset, sex, disease duration, Unified PD Rating Scale motor score, baseline Mini-Mental State Examination score, DAT activity in the posterior putamen and levodopa-equivalent daily dose (LEDD) (Hazard ratio 1.047, p = 0.002). A linear mixed model analysis revealed that patients with a higher NPI total score had a more rapid LEDD increment (NPI×time, p = 0.003). Among 52 patients with PD who eventually developed FOG during the follow-up period, there was a significant correlation between the NPI total score and time with FOG development (γ= -0.472; p = 0.001) after adjusting for confounding factors.

Conclusion: The present study demonstrated that the severity of NPS is a predictor of early freezing and motor progression in patients with PD.

Keywords: Parkinson’s disease; motor prognosis; neuropsychiatric symptoms.

MeSH terms

  • Disease Progression
  • Dyskinesia, Drug-Induced
  • Gait Disorders, Neurologic* / etiology
  • Humans
  • Levodopa / adverse effects
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / pathology

Substances

  • Levodopa