Background: Cognitive impairment strikingly reduces the quality of life of Parkinson's disease (PD) patients. Studies find that pathological proteins, neuroinflammatory factors and free radicals may involve in the pathogenesis of cognitive impairment of PD, however, results are inconclusive. Methods: We recruited 62 PD patients and 31 healthy controls. PD patients were identified with cognitive impairment, including PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD) according to the diagnostic criteria for PD-MCI and PDD issued by Movement Disorder Society Task Force. The levels of pathological proteins, including beta-amyloid 1-42 (A beta 1-42), Total-tau (T-tau) and phosphorelated tau (P-tau), neuroinflammatory factors, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interferon-gamma (INF-gamma) and prostaglandin E-2 (PGE(2)), free radicals, including hydroxyl radical (center dot OH), hydrogen peroxide (H2O2) and nitric oxide (NO) in cerebrospinal fluid (CSF) were detected. The levels of above factors in CSF were compared among healthy controls and patients with and without cognitive impairment. Correlation analyses were performed between Montreal Cognitive Assessment (MoCA) score and the levels of above factors in CSF. Results: T-tau level in CSF from PD-CI patients are significantly elevated comparing with those without cognitive impairment and controls (P=0.016 and 0.004, respectively). The levels of P-tau (S396) and center dot OH in PD-CI patients are significantly higher than controls (P=0.001 and 0.014, respectively). IL-6 levels in PD-CI patients are strikingly enhanced comparing with those without cognitive impairment (P=0.005). MoCA score is negatively correlated with the levels of T-tau (r=-0.340), P-tau (S396) (r=-0.448), IL-6 (r=-0.489) and center dot OH (r=-0.504) in PD-CI patients. Conclusions: Elevated levels of T-tau, P-tau (S396), IL-6 and center dot OH in CSF are significantly correlated with cognitive impairment in PD patients. This investigation may suggest the potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment.