Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease

Abstract

Background: C-reactive protein (CRP), a blood inflammatory biomarker, is associated with the development of Alzheimer disease. In animal models of Parkinson disease (PD), systemic inflammatory stimuli can promote neuroinflammation and accelerate dopaminergic neurodegeneration. However, the association between long-term systemic inflammations and neurodegeneration has not been assessed in PD patients.

Objective: To investigate the longitudinal effects of baseline CRP concentrations on motor prognosis in PD.

Design, setting, and participants: Retrospective analysis of 375 patients (mean age, 69.3 years; mean PD duration, 6.6 years). Plasma concentrations of high-sensitivity CRP were measured in the absence of infections, and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores were measured at five follow-up intervals (Days 1-90, 91-270, 271-450, 451-630, and 631-900).

Main outcome measure: Change of UPDRS-III scores from baseline to each of the five follow-up periods.

Results: Change in UPDRS-III scores was significantly greater in PD patients with CRP concentrations ≥0.7 mg/L than in those with CRP concentrations <0.7 mg/L, as determined by a generalized estimation equation model (P = 0.021) for the entire follow-up period and by a generalized regression model (P = 0.030) for the last follow-up interval (Days 631-900). The regression coefficients of baseline CRP for the two periods were 1.41 (95% confidence interval [CI] 0.21-2.61) and 2.62 (95% CI 0.25-4.98), respectively, after adjusting for sex, age, baseline UPDRS-III score, dementia, and incremental L-dopa equivalent dose.

Conclusion: Baseline plasma CRP levels were associated with motor deterioration and predicted motor prognosis in patients with PD. These associations were independent of sex, age, PD severity, dementia, and anti-Parkinsonian agents, suggesting that subclinical systemic inflammations could accelerate neurodegeneration in PD.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Changes in Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores (A) and L-dopa equivalent dose (LED) (B) by tertile of baseline C-reactive protein (CRP) concentrations.

UPDRS-III score and LED (mg/day) were measured at the study enrollment and during the follow-up period. Subjects were sorted by baseline CRP concentration [≤0.2 mg/L (blue), 0.3–0.6 mg/L (green), and ≥0.7 mg/L (red)]. Symbols, and upper and lower error bars represent mean and 95% CI, respectively.

Fig 2. C-reactive protein (CRP) concentrations over time in Parkinson disease (PD) patients sorted by tertile of baseline CRP concentrations.

CRP levels were measured at study enrollment and divided into tertiles [≤0.2 mg/L (blue), 0.3–0.6 mg/L (green), and ≥0.7 mg/L (red)], with CRP concentrations over time measured in each tertile. Symbols and upper and lower error bars represent median and 75th and 25th percentiles, respectively.