title: 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.
authors.affiliation: Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden; Psychiatry Skåne, Lund, Sweden. Electronic address: Daniel.Lindqvist@med.lu.se.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.forename: Sara
authors.initials: S
authors.lastname: Hall
authors.forename: Yulia
authors.initials: Y
authors.lastname: Surova
authors.forename: Henrietta M
authors.initials: HM
authors.lastname: Nielsen
authors.forename: Shorena
authors.initials: S
authors.lastname: Janelidze
authors.forename: Lena
authors.initials: L
authors.lastname: Brundin
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid; D054413:Chemokine CCL11 / Q000134:cerebrospinal fluid; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid; D054423:Chemokine CCL24 / Q000134:cerebrospinal fluid; D000075906:Chemokine CCL26; D054405:Chemokine CCL3 / Q000134:cerebrospinal fluid; D054407:Chemokine CCL4 / Q000134:cerebrospinal fluid; D019742:Chemokines, CC / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications; D003704:Dementia / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis; D003863:Depression / Q000134:cerebrospinal fluid* / Q000150:complications; D005221:Fatigue / Q000134:cerebrospinal fluid* / Q000150:complications; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid*; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: C515484:CCL24 protein, human; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: C-reactive protein; Cerebrospinal fluid; Cytokines; Dementia; Depression; Fatigue; Neuroinflammation; Parkinson’s disease