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- Halaas, Nathalie Bodd, et al.
(författare)
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Cerebrospinal Fluid Concentration of Neurogranin in Hip Fracture Patients with Delirium.
- 2021
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Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 81:2, s. 667-677
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Tidskriftsartikel (refereegranskat)abstract
- 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.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.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.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.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.
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| 2. |
- Sajjad, Muhammad Umar, et al.
(författare)
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Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 73:4, s. 1363-1372
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Tidskriftsartikel (refereegranskat)abstract
- Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known.The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium.In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer's disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay.Hip fracture patients had significantly higher IL-8 levels (p<0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p=0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p=0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p=0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients.Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.
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| 3. |
- Watne, Leiv Otto, et al.
(författare)
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Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients.
- 2023
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 133:2
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Tidskriftsartikel (refereegranskat)abstract
- The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive.We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality.In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p<0.001) to be increased, as well as increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL, β 0.43, p<0.001) and was a strong predictor of one-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, p<0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP, and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.Norwegian Health Association and the South-Eastern Norway Regional Health Authorities.
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