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      Cerebrospinal fluid levels of neopterin are elevated in delirium after hip fracture

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          Abstract

          Background

          The inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium.

          Methods

          In this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography.

          Results

          Sixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27.1 nmol/mL, p = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery ( p = 0.02 for CSF and p = 0.03 for serum).

          Conclusions

          This study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes.

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          Most cited references30

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          Diagnostic and statistical manual of mental disorders.

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            The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a review.

            The IQCODE is widely used as a screening test for dementia, particularly where the subject is unable to undergo direct cognitive testing or for screening in populations with low levels of education and literacy. This review draws together research on the psychometric properties and validity of the IQCODE. A systematic search of the literature was carried out using three databases. The review shows that the questionnaire has high reliability and measures a single general factor of cognitive decline. It validly reflects past cognitive decline, performs at least as well at screening as conventional cognitive screening tests, predicts incident dementia, and correlates with a wide range of cognitive tests. A particular strength is that the IQCODE is relatively unaffected by education and pre-morbid ability or by proficiency in the culture's dominant language. The disadvantage of the IQCODE is that it is affected by informant characteristics such as depression and anxiety in the informant and the quality of the relationship between the informant and the subject. Because the IQCODE provides information complementary to brief cognitive tests, harnessing them together can improve screening accuracy.
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              Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium.

              The DRS-R-98, a 16-item clinician-rated scale with 13 severity items and 3 diagnostic items, was validated against the Cognitive Test for Delirium (CTD), Clinical Global Impression scale (CGI), and Delirium Rating Scale (DRS) among five diagnostic groups (N=68): delirium, dementia, depression, schizophrenia, and other. Mean and median DRS-R-98 scores significantly (P<0.001) distinguished delirium from each other group. DRS-R-98 total scores correlated highly with DRS, CTD, and CGI scores. Interrater reliability and internal consistency were very high. Cutoff scores for delirium are recommended based on ROC analyses (sensitivity and specificity ranges: total, 91%-100% and 85%-100%; severity, 86%-100% and 77%-93%, respectively, depending on the cutoffs or comparison groups chosen). The DRS-R-98 is a valid measure of delirium severity over a broad range of symptoms and is a useful diagnostic and assessment tool. The DRS-R-98 is ideal for longitudinal studies.
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                Author and article information

                Contributors
                roanna.hall@gmail.com
                +47 40203712 , l.o.watne@gmail.com
                a.v.idland@medisin.uio.no
                johan.rader@medisin.uio.no
                ffrihagen@gmail.com
                a.maclullich@ed.ac.uk
                UXNNAF@ous-hf.no
                t.b.wyller@medisin.uio.no
                d.fekkes@erasmusmc.nl
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central (London )
                1742-2094
                29 June 2016
                29 June 2016
                2016
                : 13
                : 170
                Affiliations
                [ ]Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, Scotland
                [ ]Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland
                [ ]Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, PB 4950 Nydalen, N-0424 Oslo, Norway
                [ ]Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
                [ ]Institute of Clinical Medicine, University of Oslo, Oslo, Norway
                [ ]Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
                [ ]Department of Orthopedic Surgery, Oslo University Hospital, Oslo, Norway
                [ ]Department of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway
                [ ]Department of Anaesthesiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                Author information
                http://orcid.org/0000-0003-0441-6700
                Article
                636
                10.1186/s12974-016-0636-1
                4928278
                27357281
                51396e8b-4fff-41a2-96ed-9eee2899bfcf
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 February 2016
                : 21 June 2016
                Funding
                Funded by: Research Council of Norway
                Funded by: The Norwegian Association for Public Health
                Funded by: The Sophies Minde Foundation
                Funded by: Civitan Reseach Foundation
                Funded by: Research into Ageing
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100000550, British Geriatrics Society;
                Funded by: UK Medical Research Council
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Neurosciences
                delirium,dementia,csf,cellular immunity,oxidative stress
                Neurosciences
                delirium, dementia, csf, cellular immunity, oxidative stress

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