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 ◽  
...  

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.

2018 ◽  
Vol 46 (5-6) ◽  
pp. 346-357 ◽  
Author(s):  
Nathalie Bodd Halaas ◽  
Kaj Blennow ◽  
Ane-Victoria Idland ◽  
Torgeir Bruun Wyller ◽  
Johan Ræder ◽  
...  

Background: Delirium is associated with new-onset dementia, suggesting that delirium pathophysiology involves neuronal injury. Neurofilament light (NFL) is a sensitive biomarker for neuroaxonal injury. Methods: NFL was measured in cerebrospinal fluid (CSF) (n = 130), preoperative serum (n = 192), and postoperative serum (n = 280) in hip fracture patients, and in CSF (n = 123) and preoperative serum (n = 134) in cognitively normal older adults undergoing elective surgery. Delirium was diagnosed with the Confusion Assessment Method. Results: Median serum NFL (pg/mL) was elevated in delirium in hip fracture patients (94 vs. 54 pre- and 135 vs. 92 postoperatively, both p < 0.001). Median CSF NFL tended to be higher in hip fracture patients with delirium (1,804 vs. 1,636, p = 0.074). Serum and CSF NFL were positively correlated (ρ = 0.56, p < 0.001). Conclusion: Our findings support an association between neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.


2017 ◽  
Vol 7 (3) ◽  
pp. 374-385 ◽  
Author(s):  
Karen Roksund Hov ◽  
Nils Bolstad ◽  
Ane-Victoria Idland ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
...  

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.


2020 ◽  
Vol 49 (6) ◽  
pp. 604-610
Author(s):  
Joost Witlox ◽  
Dimitrios Adamis ◽  
Leo Koenderman ◽  
Kees Kalisvaart ◽  
Jos F.M. de Jonghe ◽  
...  

<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.


Gerontology ◽  
2015 ◽  
Vol 62 (4) ◽  
pp. 396-400 ◽  
Author(s):  
Susan Freter ◽  
Michael Dunbar ◽  
Katalin Koller ◽  
Chris MacKnight ◽  
Kenneth Rockwood

Background: Delirium is a common complication of hip fracture and is associated with negative outcomes. Previous studies document risk factors for post-operative delirium but have frequently excluded patients with pre-operative delirium. Objective: This study endeavours to document prevalence and risk factors for pre-operative delirium in hip fracture patients and compares risk factor profiles and outcomes between pre- and post-operative delirium. Methods: 283 hip fracture patients were assessed pre-operatively with the Delirium Elderly At Risk (DEAR) instrument, Mini-Mental State Examination (MMSE), and Confusion Assessment Method (CAM). They were followed on post-operative days 1, 3, and 5 for the presence of delirium. Doses of opioids were recorded. Wait time to surgery, length of stay, and discharge site were noted. Results: Delirium was present in 57.6% patients pre-operatively and 41.7% post-surgery. Not all patients (62%) with pre-operative delirium also had post-operative delirium. There was a considerable overlap in risk factors, with some differences. Wait time to surgery, number of comorbidities, and total pre-operative opioid and lorazepam doses were associated with pre- but not post-operative delirium. Negative outcomes were more closely associated with post-operative delirium. Conclusion: Delirium is common in pre-hip fracture surgery patients, and not all patients with pre-operative delirium go on to have post-operative delirium. Risk factor profiles are not identical, raising the possibility of identifying and intervening in patients at high risk of delirium pre-operatively.


2002 ◽  
Vol 94 (6) ◽  
pp. 1628-1632 ◽  
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Ross Anderson ◽  
...  

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A41
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Frederick E. Sieber

Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1322-1329
Author(s):  
Ivã Taiuan Fialho Silva ◽  
Pedro Assis Lopes ◽  
Tiago Timotio Almeida ◽  
Saint Clair Ramos ◽  
Ana Teresa Caliman Fontes ◽  
...  

Background and Purpose: Delirium is an acute and fluctuating impairment of attention, cognition, and behavior. Although common in stroke, studies that associate the clinical subtypes of delirium with functional outcome and death are lacking. We aimed to evaluate the influence of delirium occurrence and its different motor subtypes over stroke patients’ prognosis. Methods: Prospective cohort of stroke patients with symptom onset within 72 hours before research admission. Delirium was diagnosed by Confusion Assessment Method for the Intensive Care Unit, and its motor subtypes were defined according to the Richmond Agitation-Sedation Scale. The main outcome was functional dependence or death (modified Rankin Scale>2) at 90 days comparing: delirium versus no delirium patients; and between motor subtypes. Secondary outcomes included modified Rankin Scale score >2 at 30 days and 90-day-mortality. Results: Two hundred twenty-seven patients were enrolled. Delirium occurred in 71 patients (31.3%), with the hypoactive subtype as the most frequent, in 41 subjects (57.8%). Delirium was associated with increased risk of death and functional dependence at 30 and 90 days and higher 90-day mortality. Multivariate analysis showed delirium (odds ratio, 3.28 [95% CI, 1.17–9.22]) as independent predictor of modified Rankin Scale >2 at 90 days. Conclusions: Delirium is frequent in stroke patients in the acute phase. Its occurrence—specifically in mixed and hypoactive subtypes—seems to predict worse outcomes in this population. To our knowledge, this is the first study to prospectively investigate differences between delirium motor subtypes over functional outcome three months poststroke. Larger studies are needed to elucidate the relationship between motor subtypes of delirium and functional outcomes in the context of acute stroke.


2017 ◽  
Vol 7 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Gideon A. Caplan ◽  
JIan Tai ◽  
Fazrul Mohd Hanizan ◽  
Catherine L. McVeigh ◽  
Mark A. Hill ◽  
...  

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.


2020 ◽  
Vol 34 (5) ◽  
pp. 675-687
Author(s):  
Yan Zhang ◽  
Shu-Ting He ◽  
Bin Nie ◽  
Xue-Ying Li ◽  
Dong-Xin Wang

Abstract Background The clinical significance of emergence delirium remains unclear. The purpose of this study was to investigate the association between emergence delirium and postoperative delirium in elderly after general anesthesia and surgery. Methods This prospective observational study was done in a tertiary hospital in Beijing, China. Elderly patients (65–90 years) who underwent major noncardiac surgery under general anesthesia and admitted to the postanesthesia care unit (PACU) after surgery were enrolled. Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. Postoperative delirium was assessed with the Confusion Assessment Method during the first 5 postoperative days. The association between emergence delirium and postoperative delirium was analyzed with a multivariable logistic regression model. Results A total of 942 patients were enrolled and 915 completed the study. Emergence delirium developed in 37.0% (339/915) of patients during PACU stay; and postoperative delirium developed in 11.4% (104/915) of patients within the first 5 postoperative days. After adjusted confounding factors, the occurrence of emergence delirium is independently associated with an increased risk of postoperative delirium (OR 1.717, 95% CI 1.078–2.735, P = 0.023). Patients with emergence delirium stayed longer in PACU and hospital after surgery, and developed more non-delirium complications within 30 days. Conclusions Emergence delirium in elderly admitted to the PACU after general anesthesia and major surgery is independently associated with an increased risk of postoperative delirium. Patients with emergence delirium had worse perioperative outcomes. Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR-OOC-17012734


2002 ◽  
Vol 94 (6) ◽  
pp. 1628-1632 ◽  
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Ross Anderson ◽  
...  

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