scholarly journals Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium

2018 ◽  
Vol 46 (5-6) ◽  
pp. 346-357 ◽  
Author(s):  
Nathalie Bodd Halaas ◽  
Kaj Blennow ◽  
Ane-Victoria Idland ◽  
Torgeir Bruun Wyller ◽  
Johan Ræder ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Hip Fracture ◽  
Elective Surgery ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Neurofilament Light ◽  
Cognitively Normal ◽  
Preoperative Serum ◽  
Median Serum ◽  
Postoperative Serum

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.

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.

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 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.

Prevalence and Characteristics of Pre-Operative Delirium in Hip Fracture Patients

Gerontology ◽  
2015 ◽  
Vol 62 (4) ◽  
pp. 396-400 ◽  
Author(s):  
Susan Freter ◽  
Michael Dunbar ◽  
Katalin Koller ◽  
Chris MacKnight ◽  
Kenneth Rockwood
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Hip Fracture ◽  
Wait Time ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Negative Outcomes ◽  
Time To Surgery ◽  
Hip Fracture Surgery ◽  
Post Surgery

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.

Preoperative Factors Associated with Postoperative Change in Confusion Assessment Method Score in Hip Fracture Patients

2002 ◽  
Vol 94 (6) ◽  
pp. 1628-1632 ◽  
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Ross Anderson ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Factors Associated ◽  
Postoperative Change ◽  
Confusion Assessment ◽  
Preoperative Factors

Postoperative Change in Confusion Assessment Method (CAM) Score in Hip Fracture Patients Does Not Affect Outcome at 3 Months

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A41
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Frederick E. Sieber
Keyword(s):  
Hip Fracture ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Postoperative Change ◽  
Confusion Assessment

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.

scholarly journals Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
C. Delaby ◽  
D. Alcolea ◽  
M. Carmona-Iragui ◽  
I. Illán-Gala ◽  
E. Morenas-Rodríguez ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Lewy Bodies ◽  
Csf Biomarkers ◽  
Neurofilament Light ◽  
Cognitively Normal ◽  
Wide Range ◽  
Lateral Sclerosis ◽  
Neuroaxonal Degeneration

Abstract Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Preoperative Factors Associated with Postoperative Change in Confusion Assessment Method Score in Hip Fracture Patients

2002 ◽  
Vol 94 (6) ◽  
pp. 1628-1632 ◽  
Author(s):  
Khwaja J. Zakriya ◽  
Colleen Christmas ◽  
James F. Wenz ◽  
Shawn Franckowiak ◽  
Ross Anderson ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Factors Associated ◽  
Postoperative Change ◽  
Confusion Assessment ◽  
Preoperative Factors

scholarly journals Fatty Acid-Binding Protein 3 in Cerebrospinal Fluid of Hip Fracture Patients with Delirium

2020 ◽  
Vol 77 (1) ◽  
pp. 183-190
Author(s):  
Bjørn Erik Neerland ◽  
Nathalie Bodd Halaas ◽  
Ane Victoria Idland ◽  
Kristi Henjum ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fatty Acid ◽  
Hip Fracture ◽  
Fatty Acid Binding Protein ◽  
Neuronal Damage ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Cognitively Normal ◽  
Acid Binding Protein ◽  
Normal Controls

Background: Delirium is associated with dementia and thus biomarkers reflecting neurodegeneration are of interest. Fatty acid-binding protein 3 (FABP3) is a cytoplasmic neuronal protein that has been isolated from the brain. It is released following brain injury and concentrations in cerebrospinal fluid (CSF) are also higher in neurodegenerative disorders such as Alzheimer’s disease (AD). Objective: To examine the relationship between CSF FABP3 concentration and delirium in hip fracture patients compared to a group of cognitively normal controls. Methods: CFS FABP3 concentration was measured in 128 hip fracture patients with (n = 71) and without (n = 57) delirium, and in cognitively unimpaired adults ≥64 years (n = 124) undergoing elective surgery. Results: CSF FABP3 (pg/ml) concentration (median (IQR)) was higher in hip-fracture patients compared to cognitively normal controls (5.7 (4.2–7.7) versus 4.5 (3.4–6.1), p < 0.001). There was a significant weak correlation between age and CSF FABP3 (ρ= 0.3, p < 0.001). After adjustment for age, the association between CSF FABP3 and hip-fracture was no longer statistically significant (β= 0.05, p = 0.5). There were no significant differences in CSF FABP3 concentration between hip fracture patients with (5.4 (4.1–8.2)) and without (5.8 (4.2–7.2)) delirium. CSF FABP3 concentration correlated positively with CSF AD biomarkers p-tau (ρ= 0.7, p < 0.01) and t-tau (ρ= 0.7, p < 0.01). Conclusion: CSF FABP3 concentrations were higher in hip fracture patients compared with cognitively normal older adults, indicating ongoing age-related neurodegeneration in these patients. There were no differences of CSF FABP3 concentrations across delirium groups, suggesting that neuronal damage or degeneration reflected by FABP3 may not be directly linked to delirium pathophysiology.

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