title: Neuropsychiatric symptoms in dementia-a role for neuroinflammation?
abstract: Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.
authors.affiliation: Department of Neurobiology, Care Sciences & Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Holmgren
authors.affiliation: Department of Neurobiology, Care Sciences & Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Hjorth
authors.affiliation: Department of Neurobiology, Care Sciences & Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Schultzberg
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Lärksäter
authors.affiliation: Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ann Christine
authors.initials: AC
authors.lastname: Tysen-Bäckström
authors.affiliation: Department of Neurobiology, Care Sciences & Society (NVS), Division of Alzheimer's Disease Research Centre, Karolinska Institutet, Stockholm, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.affiliation: Department of Neurobiology, Care Sciences & Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: Yvonne.Freund-Levi@ki.se.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund-Levi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000134:cerebrospinal fluid*; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000150:complications*; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000150:complications*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D009483:Neuropsychological Tests; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Alzheimer's disease; BPSD; Behavioural symptoms; Cerebrospinal fluid; Cytokines; NPSD