| 1. |
- Eliassen, Ingvild Vøllo, et al.
(författare)
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Regression-Based Cognitive Change Norms Applied in Biochemically Defined Predementia Alzheimer’s Disease
- 2023
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Ingår i: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 37:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aim to develop 2-year cognitive change norms for adults ages 41–84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers. Background: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer’s disease (AD). Method: We developed standardized regression-based change norms from normative samples consisting of healthy controls from the Dementia Disease Initiation study (n = 125), the Trønderbrain study (n = 57), and the Gothenburg mild cognitive impairment (MCI) study (n = 65). Norms were applied in a sample with cognitive symptoms (subjective cognitive decline or MCI) and AD cerebrospinal fluid (CSF) biomarkers (n = 246), classified according to the A/T/N system. Results: The change norms adjusted for pertinent demographics and practice effects. The group with cognitive complaints displayed a trend toward cognitive decline compared to the normative group, with the A+T/N+ subgroup showing the most marked decline. This was observed in tests of episodic memory and cognitive flexibility/divided attention. Conclusions: We present 2-year cognitive change norms for adults between 41 and 84 years, adjusted for practice and demographics. A web-based change norm calculator is provided.
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| 2. |
- Gonzalez-Ortiz, Fernando, 1990, et al.
(författare)
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Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.
- 2024
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Ingår i: Nature communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n=1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
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| 3. |
- Muller, Kay, et al.
(författare)
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Analysis of protein S-100B in serum: a methodological study
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 44:9, s. 1111-1114
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dysfunction and damage of the human central nervous system can be detected with biochemical markers, and protein S-100B is the best-established such marker. The aim of this study was to evaluate whether the protein is stable during longterm storage, to establish reference values for the new Elecsys((R)) S100 test and to compare this new method with the Liaison((R)) Sangtec((R)) 100 test. Methods: We analysed blood samples from 118 blood donors and 196 patients with subarachnoid haemorrhage or head injury. The long-term stability of S-100B in frozen serum samples was evaluated with repeated analysis in 1997 and 2003 using an immunoradiometric assay. Method comparison between the Liaison((R)) Sangtec((R)) 100 and Elecsys((R)) S100 tests was performed using Bland-Altman difference plots. Results: Serum concentrations increased significantly during long-term storage (mean difference 0.15 mu g/L; +/- 2 SD, 0.55 mu g/L). Serum measurements using the Elecsys ((R)) S100 method in 118 healthy blood donors showed S-100B levels between 0.02 and 0.08 mu g/L (mean 0.05). The 95th percentile was 0.07 mu g/L. The Liaison ((R)) Sangtec((R)) 100 test usually measured higher concentrations than the Elecsys((R)) S100 method, and the difference between the two methods increased with increasing concentrations. The mean difference between the methods was 0.14 mu g/L (+/- 2 SD, 0.39 mu g/L). Conclusions: Protein S-100B is not stable during longterm storage and the two analytical methods are not interchangeable.
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| 4. |
- Muller, Kay, et al.
(författare)
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S100B serum level predicts computed tomography findings after minor head injury
- 2007
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Ingår i: Journal of Trauma. - 0022-5282. ; 62:6, s. 1452-1456
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild head injury (MHI) implies a risk for traumatic brain injury and even a small risk for development of an intracranial hematoma. Head computed tomography (CT) is recommended for early detection of such pathologic findings. The present multicenter study was performed to investigate whether determination of protein S100B in serum could contribute to the selection of patients for CT scanning. Methods: We included 226 patients with a history of head injury and a Glasgow Coma Scale (GCS) score of 13 to 15 at admission to hospital. Blood samples for S100B analysis and head CT were obtained within 12 hours after the injury. The diagnostic properties of S100B measurements for prediction of intracranial injury revealed by CT were tested with receiver operating characteristic (ROC) analysis and cross-table analysis at different cut-off levels. We also included analysis of S100B levels normalized to correspond to blood sampling I hour after the injury. Results: CT showed intracranial injury in 21 (9.3%) patients. S100B levels were significantly (p < 0.001) elevated in patients with intracranial injury (mean, 0.36; 95% CI, 0.21-0.50 mu g/L) compared with those in patients without intracranial injury (mean, 0.18; 95% CI, 0.16-0.20 mu g/L). ROC curve analysis showed a significant (p = 0.001) area under the curve (0.73; 95% CI, 0.62-0.84). Cross-table analysis showed that 20 of 21 (sensitivity 0.95) patients with intracranial injury were detected at a cut-off level of 0.10 mu g/L, but 141 of 205 (specificity 0.31) patients with no such injury also had a S100B level above this limit. Exclusion of cases with blood samples collected more than 3 hours after injury or normalization did not improve the diagnostic properties. Conclusion: Determination of serum S100B cannot replace the clinical examination or use of CT for patients with minor head injury, but adding S100B measurement to the clinical evaluation might support selection of patients for CT scanning.
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| 5. |
- Nordengen, Kaja, et al.
(författare)
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Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer's disease.
- 2023
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Ingår i: Journal of neuroinflammation. - 1742-2094. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Brain innate immune activation is associated with Alzheimer's disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles.We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline (n=535) and follow-up (n=213), between 1 and 6years from baseline (mean 2.8years). We measured Aβ42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A-/T-/N-, A+/T-/N-, A+/T+ or N+, or A-/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group.Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p<0.001, A+/T+ or N+ and A-/T+ or N+, compared to A-/T-/N-). No significant group differences were observed for the cytokines CSF MCP-1, IL-6, IL-10, IL18 or IFN-γ. Longitudinally, CSF YKL-40, fractalkine and IFN-γ were all significantly lower in stable A+/T-/N- cases (all p<0.05). CSF sTREM2, YKL-40, clusterin, fractalkine (p<0.001) and MCP-1 (p<0.05) were all higher in T or N+, with or without amyloidosis at baseline, but remained stable over time. High CSF sTREM2 was associated with preserved cognitive function within the A+/T+ or N+ group, relative to the cognitively impaired with the same A/T/N biomarker profile (p<0.01).Immune hypoactivation and reduced neuron-microglia communication are observed in isolated amyloidosis while activation and increased fractalkine accompanies tau pathology in predementia AD. Glial hypo- and hyperactivation through the predementia AD continuum suggests altered glial interaction with Ab and tau pathology, and may necessitate differential treatments, depending on the stage and patient-specific activation patterns.
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| 6. |
- Unden, Johan, et al.
(författare)
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Clinical significance of serum S100B levels in neurointensive care
- 2007
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Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 6:2, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- Objective S100B is viewed as the most promising biomarker for brain damage. It has been proposed that this marker is useful in a Neurointensive Care Unit (NICU) as a monitoring parameter. This study aims to examine the clinical usefulness of daily serum S100B measurements in this setting. Design Prospective consecutive inclusion of patients. Patients A total of 79 patients with confirmed or suspected head injury or cerebrovascular insults (CVIs) (based upon patient history, computed tomography (CT) and/or magnetic resonance imaging (MRI) and neurological examination including coma scoring) who required neurointensive care were included in the study. Interventions Sampling for S100B was performed at admission and daily until patients were discharged from the NICU. S100B measurements were statistically compared to occurrence of secondary complications and outcome according to Glasgow Outcome Scale (GOS), with focus on clinical prediction. Measurements and main results 17 of 79 patients (22%) had secondary neurological complications. Mean S100B levels were found to be an independent parameter associated with these complications (P = 0.03). Mean S100B levels were higher in patients with complications compared to those without on both the complication day (P = 0.033) and the day after (P = 0.015), but not the day prior to the complication (P = 0.62). S100B did not predict secondary neurological complication. Neither mean (P = 0.182) nor peak (P = 0.370) S100B levels were associated with or predicted outcome according to dichotornised GOS. Conclusion Daily S100B measurements are associated with secondary complications but not to outcome. However, daily S100B levels do not predict secondary complications, which limit the usefulness of this brain biomarker in this setting.
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