Blood-Cerebrospinal Fluid Barrier Integrity in Delirium Determined by Q-Albumin

2016 ◽  
Vol 41 (3-4) ◽  
pp. 192-198 ◽  
Author(s):  
Karen Roksund Hov ◽  
Jens Petter Berg ◽  
Frede Frihagen ◽  
Johan Ræder ◽  
Roanna Hall ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Serum Albumin ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
University Hospital ◽  
Barrier Dysfunction ◽  
Barrier Integrity ◽  
Subsyndromal Delirium ◽  
Hospitalised Patients ◽  
Low Prevalence

Background/Aims: Delirium is a common and serious complication in hospitalised patients and its pathophysiology is incompletely understood. We aimed to examine whether blood-cerebrospinal fluid barrier dysfunction, as measured by Q-albumin (the ratio of cerebrospinal fluid albumin to serum albumin), was associated with delirium. Methods: In this prospective cohort study of hip fracture patients from Oslo University Hospital, Norway, serum was collected preoperatively and cerebrospinal fluid just before the onset of spinal anaesthesia. Albumin levels in serum and cerebrospinal fluid were analysed consecutively, and Q-albumin was calculated using the formula [cerebrospinal fluid albumin (mg/dl) × 1,000]/[serum albumin (mg/dl)]. Q-albumin >10.2 was used as the cut-off for blood-cerebrospinal fluid barrier dysfunction. Patients were assessed daily for delirium using the Confusion Assessment Method. Results: Out of 120 patients, 69 had delirium, 22 had subsyndromal delirium, and 29 were free from delirium. The majority of patients, i.e. 106 (88%), had intact blood-cerebrospinal fluid barrier integrity, but all 14 patients with blood-cerebrospinal barrier dysfunction had delirium (n = 11) or subsyndromal delirium (n = 3). Conclusions: The results suggest that blood-cerebrospinal fluid barrier dysfunction may be relevant for delirium pathophysiology when it occurs. However, the low prevalence (16% of delirium patients) indicates that this is not a prerequisite for the development of delirium.

scholarly journals Cerebrospinal Fluid S100B and Alzheimer’s Disease Biomarkers in Hip Fracture Patients with Delirium

2017 ◽  
Vol 7 (3) ◽  
pp. 374-385 ◽  
Author(s):  
Karen Roksund Hov ◽  
Nils Bolstad ◽  
Ane-Victoria Idland ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Hip Fracture ◽  
Elective Surgery ◽  
Hospital Setting ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
University Hospital ◽  
Significant Difference ◽  
Fracture Population ◽  
Available Information

Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electrochemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 μg/L [0.91–1.29]) and patients who never developed delirium (n = 46, 1.08 μg/L [0.92–1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 μg/L [1.08–1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (≥60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology.

scholarly journals Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

2015 ◽  
Vol 36 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Sara Shams ◽  
Tobias Granberg ◽  
Juha Martola ◽  
Xiaozhen Li ◽  
Mana Shams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Serum Albumin ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Csf Biomarkers ◽  
Barrier Dysfunction ◽  
T Tau

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment ( p < 0.05). CSF/serum albumin ratios were high with multiple CMBs ( p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease ( p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

scholarly journals Twelve-Month Mortality Among Delirium Subtypes

2011 ◽  
Vol 20 (4) ◽  
pp. 404-421 ◽  
Author(s):  
Susan K. DeCrane ◽  
Kennith R. Culp ◽  
Bonnie Wakefield
Keyword(s):  
Statistical Significance ◽  
The Elderly ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Term Care ◽  
International Classification Of Disease ◽  
Subsyndromal Delirium ◽  
Icd 10 ◽  
Underlying Cause Of Death ◽  
State Examination

This study used data from the Delirium Among the Elderly in Rural Long-Term Care Facilities Study and data from the National Death Index (NDI) to examine mortality among 320 individuals. Individuals were grouped into noncases, subsyndromal cases, hypoactive delirium, hyperactive delirium, and mixed delirium on the basis of scoring using the Confusion Assessment Method (CAM), NEECHAM Scale, Mini-Mental State Examination (MMSE), Clinical Assessment of Confusion-A (CAC-A), and Vigilance A instruments. Risk ratios of mortality using “days of survival” did not reach statistical significance (α = .05) for any subgroup. Underlying cause of death (UCD) using International Classification of Disease, 10th version (ICD-10), showed typical UCD among older adults. There appeared to be clinical differences in UCD between delirium subgroups. Findings supported the conclusion that careful monitoring of patients with delirium and subsyndromal delirium is needed to avoid complications and injuries that could increase mortality.

scholarly journals Cerebrospinal Fluid Apolipoprotein E Levels in Delirium

2017 ◽  
Vol 7 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Gideon A. Caplan ◽  
JIan Tai ◽  
Fazrul Mohd Hanizan ◽  
Catherine L. McVeigh ◽  
Mark A. Hill ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cerebrospinal Fluid ◽  
Apolipoprotein E ◽  
Late Onset ◽  
The Elderly ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Apolipoprotein A1 ◽  
Ε4 Allele ◽  
State Examination

Background/Aims: Delirium and the apolipoprotein E ε4 allele are risk factors for late-onset Alzheimer disease (LOAD), but the connection is unclear. We looked for an association. Methods: Inpatients with delirium (n = 18) were compared with LOAD outpatients (n = 19), assaying blood and cerebrospinal fluid (CSF) using multiplex ELISA. Results: The patients with delirium had a higher Confusion Assessment Method (CAM) score (5.6 ± 1.2 vs. 0.0 ± 0.0; p < 0.001) and Delirium Index (13.1 ± 4.0 vs. 2.9 ± 1.2; p = 0.001) but a lower Mini-Mental State Examination (MMSE) score (14.3 ± 6.8 vs. 20.8 ± 4.6; p = 0.003). There was a reduction in absolute CSF apolipoprotein E level during delirium (median [interquartile range]: 9.55 μg/mL [5.65–15.05] vs. 16.86 μg/mL [14.82–20.88]; p = 0.016) but no differences in apolipoprotein A1, B, C3, H, and J. There were no differences in blood apolipoprotein levels, and no correlations between blood and CSF apolipoprotein levels. CSF apolipoprotein E correlated negatively with the CAM score (r = –0.354; p = 0.034) and Delirium Index (r = –0.341; p = 0.042) but not with the Acute Physiology and Chronic Health Evaluation (APACHE) index, or the MMSE or Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Conclusion: Reduced CSF apolipoprotein E levels during delirium may be a mechanistic link between two important risk factors for LOAD.

Early detection of delirium – using the CAM score

2019 ◽  
Vol 2 (3) ◽  
pp. 50
Author(s):  
Lise Rekvad
Keyword(s):  
Emergency Department ◽  
Health Care Providers ◽  
Research Team ◽  
Clinical Importance ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
University Hospital ◽  
Care Providers ◽  
Old Patients ◽  
Hospital Acquired

Background: Delirium is common in elderly patients and has been identified as an independent marker for increased mortality and hospital-acquired complications, yet it is poorly recognized by health care providers. The aim of this study was to investigate whether systematic use of the validated screening tool Confusion Assessment Method (CAM) would result in a higher recognizing of delirium in patients ≥ 65 years old admitted at Odense Emergency Department (FAM). Methods: All caregivers in the Emergency department (ED) at Odense University Hospital received 2 hours of education in delirium and how to use the CAM score. They were asked to systematically perform CAM score in all patients ≥ 65 years at arrival to the ED and at least every 8 hours.  During 2 periods of 5 days - one before the caregivers was educated (pre-CAM) and one 4 weeks after CAM scoring was started (during-CAM). A research team interviewed all ≥ 65 year old patients and their caregivers at the first and second day of admission. In relation to the interviews all patients underwent a cognitive assessment using the CAM by a trained investigator. These results were blinded to the clinical personal. After discharge patient files were screened with the aim to identify any delirium registered by the clinical personal. Results: Out of 276 screened patients 192 where included in the project. 100 patients and were included in the pre-CAM group and 92 patients in the during-CAM group. According to the registrations by the research team 24 of 100 (24% 95%CI 16%-34%) patients experience delirium in the pre-CAM group and 18 of 92 (20% 95%CI 12%-29%) in the during-CAM group. Increasing age and comorbidity was related to delirium.  Prevalence of the diagnoses delirium registered in the patient file increased from 1 of 24 (4% 95%CI  0%-21%) to 9 of 18 (50% 95%CI 26%-74%). Conclusion: One out of four elderly acute patients has deliria symptoms during the first 2 days at hospital. Systematic CAM scoring does not change the prevalence but increase the awareness significantly. The high prevalence underlines the clinical importance of the problem.

scholarly journals Assessment of Delirium Using the Confusion Assessment Method in Older Adult Inpatients in Malaysia

Geriatrics ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. 52
Author(s):  
Khor ◽  
Ong ◽  
Tan ◽  
Low ◽  
Saedon ◽  
...  
Keyword(s):  
Older Patients ◽  
Altered Mental Status ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Assessment Tools ◽  
University Hospital ◽  
Cognitive Screening ◽  
Cross Sectional ◽  
Confusion Assessment ◽  
Severity Scores

The detection of delirium in acutely ill older patients is challenging with the lack of informants and the necessity to identify subtle and fluctuating signs. We conducted a cross-sectional study among older patients admitted to a university hospital in Malaysia to determine the presence, characteristics, and mortality outcomes of delirium. Consecutive patients aged ≥65years admitted to acute medical wards were recruited from August to September 2016. Cognitive screening was performed using the mini-mental test examination (MMSE) and the Confusion Assessment Method (CAM). The CAM-Severity (CAM-S) score was also performed in all patients. Of 161 patients recruited, 43 (26.7%) had delirium. At least one feature of delirium from the CAM-S short and long severity scores were present in 48.4% and 67.1%, respectively. Older age (OR: 1.07, 95% CI: 1.01–1.14), immobility (OR: 3.16, 95% CI: 1.18–8.50), cognitive impairment (OR: 5.04, 95% CI: 2.07–12.24), and malnutrition (OR: 3.37; 95% CI: 1.15–9.85) were significantly associated with delirium. Older patients with delirium had a higher risk of mortality (OR: 7.87, 95% CI: 2.42–25.57). Delirium is common among older patients in our setting. A large proportion of patients had altered mental status on admission to hospital although they did not fulfill the CAM criteria of delirium. This should prompt further studies on strategies to identify delirium and the use of newer, more appropriate assessment tools in this group of vulnerable individuals.

scholarly journals Cerebrospinal Fluid Concentration of Neurogranin in Hip Fracture Patients with Delirium

2021 ◽  
pp. 1-11
Author(s):  
Nathalie Bodd Halaas ◽  
Henrik Zetterberg ◽  
Ane-Victoria Idland ◽  
Anne-Brita Knapskog ◽  
Leiv Otto Watne ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Hip Fracture ◽  
Elective Surgery ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Sensitivity Analyses ◽  
Synaptic Dysfunction ◽  
Increased Risk ◽  
Fluid Concentration ◽  
Early Alzheimer’S Disease

Background: Delirium is associated with an increased risk of incident dementia and accelerated progression of existing cognitive symptoms. Reciprocally, dementia increases the risk of delirium. Cerebrospinal fluid (CSF) concentration of the dendritic protein neurogranin has been shown to increase in early Alzheimer’s disease (AD), likely reflecting synaptic dysfunction and/or degeneration. Objective: To elucidate the involvement of synaptic dysfunction in delirium pathophysiology, we tested the association between CSF neurogranin concentration and delirium in hip fracture patients with different AD-biomarker profiles, while comparing them to cognitively unimpaired older adults (CUA) and AD patients. Methods: The cohort included hip fracture patients with (n = 70) and without delirium (n = 58), CUA undergoing elective surgery (n = 127), and AD patients (n = 46). CSF was collected preoperatively and diagnostically in surgery and AD patients respectively. CSF neurogranin concentrations were analyzed in all samples with an in-house ELISA. Delirium was assessed pre-and postoperatively in hip fracture patients by trained investigators using the Confusion Assessment Method. Hip fracture patients were further stratified based on pre-fracture dementia status, delirium subtype, and AD fluid biomarkers. Results: No association was found between delirium and CSF neurogranin concentration (main analysis: delirium versus no delirium, p = 0.68). Hip fracture patients had lower CSF neurogranin concentration than AD patients (p = 0.001) and CUA (p = 0.035) in age-adjusted sensitivity analyses. Conclusion: The findings suggest that delirium is not associated with increased CSF neurogranin concentration in hip fracture patients, possibly due to advanced neurodegenerative disease and age and/or because synaptic degeneration is not an important pathophysiological process in delirium.

Delirium in elderly patients: association with educational attainment

2016 ◽  
Vol 29 (2) ◽  
pp. 95-101 ◽  
Author(s):  
Sónia Martins ◽  
José Artur Paiva ◽  
Mário R. Simões ◽  
Lia Fernandes
Keyword(s):  
Elderly Patients ◽  
Educational Attainment ◽  
Cognitive Reserve ◽  
Statistical Significance ◽  
Strong Association ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Final Sample ◽  
Hospitalised Patients ◽  
Definition Of

ObjectiveAmong cognitive reserve markers, educational attainment is the most widely studied, with several studies establishing a strong association with risk of dementia. However, it has not yet been fully examined in delirium. This study aims to analyse the relationship between educational attainment and delirium.MethodsThe study included elderly hospitalised patients admitted (≥48 h) into an intermediate care unit (IMCU) of Intensive Care Medicine Service. Exclusion criteria were as follows: Glasgow Coma Scale (total≤11), blindness/deafness, inability to communicate or to speak Portuguese. The European Portuguese Version of the Confusion Assessment Method (CAM) was used for delirium assessment.ResultsThe final sample (n=157) had a mean age of 78.8 (SD=7.6) the majority being female (52.2%), married (51.5%) and with low educational level (49%). According to CAM, 21% of the patients had delirium. The delirium group presented the fewest years of education (median 1 vs. 4), with statistical significance (p=0.003). Delirium was more frequent among male patients [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.12–0.86; p=0.023], as well as those patients with lower education (OR 0.76; 95% CI 0.62–0.95; p=0.016), and with respiratory disease (OR 3.35; 95% CI 1.20–9.33; p=0.020), after controlling for age and medication.ConclusionSimilar to previous studies, these findings point to a negative correlation between education and delirium. This study appears as an attempt to contribute to the knowledge about the role of cognitive reserve in risk of delirium, particularly because is the first one that has been carried out in an IMCU, with lower educated elderly patients. Further studies are needed to clarify this relationship considering other markers (e.g. cognitive activities), which can contribute to the definition of preventive strategies.

scholarly journals Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients

2020 ◽  
Vol 49 (6) ◽  
pp. 604-610
Author(s):  
Joost Witlox ◽  
Dimitrios Adamis ◽  
Leo Koenderman ◽  
Kees Kalisvaart ◽  
Jos F.M. de Jonghe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cerebrospinal Fluid ◽  
Hip Fracture ◽  
Postoperative Delirium ◽  
Rating Scale ◽  
The Elderly ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Cortisol Levels ◽  
A Prospective Study

<b><i>Background:</i></b> Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. <b><i>Objectives:</i></b> We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. <b><i>Methods:</i></b> In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. <b><i>Results:</i></b> Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. <b><i>Conclusions:</i></b> These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients.

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