| 1. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 2. |
- Aam, Stina, et al.
(författare)
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The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment : The Nor-COAST Study
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR =12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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