Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression, fatigue, and cognitive impairment

Abstract

Neuroinflammation may be involved in the pathophysiology of Parkinson's disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation. We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N=87) and the reference group (N=33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively. There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p=0.032) and the reference group (p=0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p=0.010) and fatigue (p=0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p=0.032). Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.

Parkinsonism in Patients With Chronic Hepatitis C Treated With Interferons

“…22,23,30,34 A recent clinical study examining cerebrospinal fluid revealed that C-reactive protein and monocyte chemotactic protein-1 were elevated in patients with PD and correlated with more severe symptoms of depression, a nonmotor complication of PD. 35 Of note, there were no meaningful changes in IL-6, TNF-α, or interferon gamma-induced protein-10. Clinically, positron emission tomography brain imaging with a benzodiazepine ligand reveals microglial activation in the basal ganglia and frontal and temporal cortices in patients with PD.…”

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

“…56 Measures of CSF markers, including C-reactive protein, interleukin 6, TNF-α, interferon 10, monocyte chemotactic protein 1, and macrophage inflammatory protein 1-β, in individuals with PD found inflammatory markers to be significantly associated with more severe depression, anxiety, fatigue, and cognition. 57 These independent lines of evidence therefore support inflammation as an important pathway in PD, in which perturbations might serve as biomarkers with different purposes.…”

Recognition and treatment of neuropsychiatric disturbances in Parkinson’s disease

“…Early in the development of dopamine transporter scan use in PD, a report linking low binding to anxiety was published [84]. Cerebrospinal fluid cytokine levels have more recently been shown to correlate with anxiety as well as depression and fatigue [85]. These results must be considered tentative.…”