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Sökning: WFRF:(Blennow Fredrik)

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1.
  • Andersson, Annika, et al. (författare)
  • Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease
  • 2019
  • Ingår i: Clinica Chimica Acta. - : Elsevier B.V.. - 0009-8981 .- 1873-3492. ; 494, s. 79-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.
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3.
  • Austeng, Dordi, et al. (författare)
  • Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
  • 2010
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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4.
  • Blennow, Kristina, et al. (författare)
  • Implementing storm damage in a dynamic vegetation model for regional applications in Sweden
  • 2012
  • Ingår i: Ecological Modelling. - : Elsevier BV. - 0304-3800 .- 1872-7026. ; 247, s. 71-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Wind is the dominant agent of damage in forests in Western Europe. Traditional wind-damage models calculate a probability for damage or a critical wind speed at which damage occurs. However, in a dynamic vegetation model actual damage to stands and individual trees is needed to get a dynamical progression of the vegetation. We present a prototype for a new approach to modelling forest wind damage at the regional scale, which we incorporate within a dynamic vegetation model. The approach is based on knowledge from both empirical and mechanical models and calculates the damaged fraction of a cohort based on wind load and a sensitivity that depends on the current physical state and history of the cohort in relation to the ecosystem. The modelling concept has been developed, calibrated and evaluated for Swedish conditions but can be applicable to other similar areas with minor modification. Because of the stochastic nature of local wind load and the difficulty of describing the stand-level exposure, the ability to explain observed damage at stand level was low. Regional level variation in damage, which more depends on the wind load, was however explained reasonably well (R-2 = 0.43). We suggest that this is a useful concept for evaluating alternatives of forest management under different climate scenarios in the process of adaptation to future storm-damage risks. (C) 2012 Elsevier B.V. All rights reserved.
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5.
  • Boström, Fredrik, et al. (författare)
  • Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.
  • 2009
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 314-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.
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  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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8.
  • Constantinescu, Radu, 1966, et al. (författare)
  • Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.
  • 2017
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 306, s. 25-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.
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9.
  • Constantinescu, Radu, 1966, et al. (författare)
  • Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis
  • 2016
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101. ; 23:4, s. 796-806
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purposeClinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. MethodsDemographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. ResultsThe acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. ConclusionIn autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.
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10.
  • Danielsson, Mattias, et al. (författare)
  • Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
  • 2021
  • Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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12.
  • Fellman, Vineta, et al. (författare)
  • One-year survival of extremely preterm infants after active perinatal care in Sweden.
  • 2009
  • Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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13.
  • Gustavsson, Jaana, 1974, et al. (författare)
  • Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women.
  • 2012
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 220:2, s. 486-492
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk. METHODS: Combining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates. RESULTS: Smoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00-2.10) in ɛ2 carriers, 2.25 (95% CI 1.90-2.68) in ɛ3 homozygotes and 2.37 (95% CI 1.85-3.04) in ɛ4 carriers. Female ɛ4 carriers had OR 3.62 (95% CI 2.32-5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73-1.61), 1.34 (95% CI 1.12-1.61), and 1.79 (95% CI 1.38-2.30) in ɛ2, ɛ3ɛ3 and ɛ4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels. CONCLUSION: The APOE ɛ2 allele counteracted CHD risk from smoking in both genders, while the ɛ4 allele was seen to potentiate this risk mainly in women. Similar ɛ2 protection and ɛ4 potentiation was suggested for CHD risk from physical inactivity.
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15.
  • Khalil, Michael, et al. (författare)
  • Neurofilaments as biomarkers in neurological disorders - towards clinical application.
  • 2024
  • Ingår i: Nature Reviews Neurology. - 1759-4758 .- 1759-4766. ; 20:5, s. 269-287
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.
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16.
  • Kläppe, Ulf, et al. (författare)
  • Neurodegenerative biomarkers outperform neuroinflammatory biomarkers in amyotrophic lateral sclerosis.
  • 2023
  • Ingår i: Amyotrophic lateral sclerosis & frontotemporal degeneration. - 2167-9223. ; 25:1-2, s. 150-61
  • Tidskriftsartikel (refereegranskat)abstract
    • To describe the diagnostic and prognostic performance, and longitudinal trajectories, of potential biomarkers of neuroaxonal degeneration and neuroinflammation in amyotrophic lateral sclerosis (ALS).This case-control study included 192 incident ALS patients, 42 ALS mimics, 114 neurological controls, and 117 healthy controls from Stockholm, Sweden. Forty-four ALS patients provided repeated measurements. We assessed biomarkers of (1)neuroaxonal degeneration: neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF) and NfL in serum, and (2)neuroinflammation: chitotriosidase-1 (CHIT1) and monocyte chemoattractant protein 1 (MCP-1) in CSF. To evaluate diagnostic performance, we calculated the area under the curve (AUC). To estimate prognostic performance, we applied quantile regression and Cox regression. We used linear regression models with robust standard errors to assess temporal changes over time.Neurofilaments performed better at differentiating ALS patients from mimics (AUC: pNfH 0.92, CSF NfL 0.86, serum NfL 0.91) than neuroinflammatory biomarkers (AUC: CHIT1 0.71, MCP-1 0.56). Combining biomarkers did not improve diagnostic performance. Similarly, neurofilaments performed better than neuroinflammatory biomarkers at predicting functional decline and survival. The stratified analysis revealed differences according to the site of onset: in bulbar patients, neurofilaments and CHIT1 performed worse at predicting survival and correlations were lower between biomarkers. Finally, in bulbar patients, neurofilaments and CHIT1 increased longitudinally but were stable in spinal patients.Biomarkers of neuroaxonal degeneration displayed better diagnostic and prognostic value compared with neuroinflammatory biomarkers. However, in contrast to spinal patients, in bulbar patients neurofilaments and CHIT1 performed worse at predicting survival and seemed to increase over time.
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17.
  • Krifors, Anders, et al. (författare)
  • Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden : a prospective multicentre cohort study
  • 2024
  • Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 56:2, s. 110-115
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.
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18.
  • Lövheim, Hugo, et al. (författare)
  • Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease
  • 2017
  • Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:7, s. 778-782
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)—central in the pathogenesis of AD—is a logical candidate, but studies to date have produced conflicting results on its utility.Methods: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNO-BIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42.Results: Plasma concentrations of free Aβ40 and Aβ42 did not differ between preclinical AD cases and dementia-free controls, in the full sample or in subgroups defined according to sex and age group (<60 and ≥ 60 years). The interval between sampling and AD diagnosis did not affect the results. Aβ concentrations did not change in the years preceding AD diagnosis among individuals for whom longitudinal samples were available.Discussion: Plasma concentrations of free Aβ could not predict the development of clinical AD, and Aβ concentrations did not change in the years preceding AD diagnosis in this sample. These results indicate that free plasma Aβ is not a useful biomarker for the identification of individuals at risk of developing clinical AD.
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19.
  • Marklund, Niklas, et al. (författare)
  • Tau aggregation and increased neuroinflammation in athletes after sports-related concussions and in traumatic brain injury patients – A PET/MR study
  • 2021
  • Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 30
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) and repeated sports-related concussions (rSRCs) are associated with an increased risk for neurodegeneration. Autopsy findings of selected cohorts of long-term TBI survivors and rSRC athletes reveal increased tau aggregation and a persistent neuroinflammation. To assess in vivo tau aggregation and neuroinflammation in young adult TBI and rSRC cohorts, we evaluated 9 healthy controls (mean age 26 ± 5 years; 4 males, 5 females), 12 symptomatic athletes (26 ± 7 years; 6 males, 6 females) attaining ≥3 previous SRCs, and 6 moderate-to severe TBI patients (27 ± 7 years; 4 males, 2 females) in a combined positron emission tomography (PET)/magnetic resonance (MR) scanner ≥6 months post-injury. Dual PET tracers, [18F]THK5317 for tau aggregation and [11C]PK11195 for neuroinflammation/microglial activation, were investigated on the same day. The Repeated Battery Assessment of Neurological Status (RBANS) scores, used for cognitive evaluation, were lower in both the rSRC and TBI groups (p < 0.05). Neurofilament-light (NF-L) levels were increased in plasma and cerebrospinal fluid (CSF; p < 0.05), and serum tau levels lower, in TBI although not in rSRC. In rSRC athletes, PET imaging showed increased neuroinflammation in the hippocampus and tau aggregation in the corpus callosum. In TBI patients, tau aggregation was observed in thalami, temporal white matter and midbrain; widespread neuroinflammation was found e.g. in temporal white matter, hippocampus and corpus callosum. In mixed-sex cohorts of young adult athletes with persistent post-concussion symptoms and in TBI patients, increased tau aggregation and neuroinflammation are observed at ≥6 months post-injury using PET. Studies with extended clinical follow-up, biomarker examinations and renewed PET imaging are needed to evaluate whether these findings progress to a neurodegenerative disorder or if spontaneous resolution is possible.
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20.
  • Mattsson, Niklas, 1979, et al. (författare)
  • BACE1 inhibition induces a specific cerebrospinal fluid β-amyloid pattern that identifies drug effects in the central nervous system.
  • 2012
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACE1 is a key enzyme for amyloid-β (Aβ) production, and an attractive therapeutic target in Alzheimer's disease (AD). Here we report that BACE1 inhibitors have distinct effects on neuronal Aβ metabolism, inducing a unique pattern of secreted Aβ peptides, analyzed in cell media from amyloid precursor protein (APP) transfected cells and in cerebrospinal fluid (CSF) from dogs by immunoprecipitation-mass spectrometry, using several different BACE1 inhibitors. Besides the expected reductions in Aβ1-40 and Aβ1-42, treatment also changed the relative levels of several other Aβ isoforms. In particular Aβ1-34 decreased, while Aβ5-40 increased, and these changes were more sensitive to BACE1 inhibition than the changes in Aβ1-40 and Aβ1-42. The effects on Aβ5-40 indicate the presence of a BACE1 independent pathway of APP degradation. The described CSF Aβ pattern may be used as a pharmacodynamic fingerprint to detect biochemical effects of BACE1-therapies in clinical trials, which might accelerate development of novel therapies.
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21.
  • Mehlig, Kirsten, 1964, et al. (författare)
  • The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
  • 2013
  • Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 99:23, s. 1761-1765
  • Tidskriftsartikel (refereegranskat)abstract
    • An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
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22.
  • Minta, Karolina, et al. (författare)
  • Cerebrospinal fluid brevican and neurocan fragment patterns in human traumatic brain injury.
  • 2021
  • Ingår i: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492 .- 0009-8981. ; 512, s. 74-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Altered levels of two extracellular matrix (ECM) proteoglycans, brevican and neurocan, have been found in brain injury models; however, their proteolytic processing in traumatic brain injury (TBI) remains unexplored. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a possible contributor to ECM remodelling following TBI. The aims of this study were to evaluate proteolytic brevican/neurocan patterns and ADAMTS-like activity in cerebrospinal fluid (CSF) in the context of TBI.Forty-two acute TBI patients and 37 idiopathic normal pressure hydrocephalus (iNPH) patients were included in the analysis of tryptic brevican and neurocan peptides in CSF using parallel reaction monitoring mass spectrometry. Twenty-nine TBI and 36 iNPH patients were analysed for ADAMTS-like activity in CSF using a quenched fluorescent substrate.The majority of CSF concentrations of brevican peptides significantly decreased in TBI patients compared with the iNPH group (p≤0.002), while ADAMTS-like activity increased (p<0.0001). Two C-terminal brevican peptides strongly correlated with unfavourable outcome of TBI patients (rho=0.85-0.93, p≤0.001).The decreased CSF concentrations of brevican peptides in TBI are associated with their increased degradation by ADAMTS enzymes. Furthermore, the N- and C- terminal parts of brevican are differentially regulated following TBI and may serve as outcome markers.
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23.
  • Needham, Edward J, et al. (författare)
  • Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury.
  • 2021
  • Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 207:1, s. 90-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognized prognostic factors. Neuroinflammation may account for some of this difference. We hypothesized that TBI generated variable autoantibody responses between individuals that would contribute to outcome. We developed a custom protein microarray to detect autoantibodies to both CNS and systemic Ags in serum from the acute-phase (the first 7 d), late (6-12 mo), and long-term (6-13 y) intervals after TBI in human patients. We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of Ags tested, predominantly IgM mediated in the acute phase, then IgG dominant at late and long-term time points. The second was responses to specific Ags, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved. Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year postinjury. Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses means that conventional approaches based on measuring responses to single antigenic targets may be misleading.
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24.
  • Neselius, Sanna, et al. (författare)
  • Monitoring concussion in a knocked-out boxer by CSF biomarker analysis.
  • 2015
  • Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 23:9, s. 2536-2539
  • Tidskriftsartikel (refereegranskat)abstract
    • Concussion is common in many sports, and the incidence is increasing. The medical consequences after a sport-related concussion have received increased attention in recent years since it is known that concussions cause axonal and glial damage, which disturbs the cerebral physiology and makes the brain more vulnerable for additional concussions. This study reports on a knocked-out amateur boxer in whom cerebrospinal fluid (CSF) neurofilament light (NFL) protein, reflecting axonal damage, was used to identify and monitor brain damage. CSF NFL was markedly increased during 36weeks, suggesting that neuronal injury persists longer than expected after a concussion. CSF biomarker analysis may be valuable in the medical counselling of concussed athletes and in return-to-play considerations. Level of evidence IV.
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25.
  • Nilsson, Jonas, 1970, et al. (författare)
  • Synthetic standard aided quantification and structural characterization of amyloid-beta glycopeptides enriched from cerebrospinal fluid of Alzheimer's disease patients
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An early pathological hallmark of Alzheimer's disease (AD) is amyloid-beta (A beta) deposits in the brain, which largely consist of up to 43 amino acids long A beta peptides derived from the amyloid precursor protein (APP). We previously identified a series of sialylated Tyr-10 O-glycosylated A beta peptides, 15-20 residues long, from human cerebrospinal fluid (CSF) and observed a relative increase of those in AD vs non-AD patients. We report here on the synthesis and use of an isotopically double-labeled A beta 1-15 glycopeptide, carrying the core 1Gal beta 3GalNAc alpha 1-O-Tyr-10 structure, to (1) identify by HCD LC-MS/MS the definite glycan core 1 structure of immunopurified and desialylated A beta glycopeptides in human CSF and to (2) establish a LC-MS/MS quantification method for desialylated A beta 1-15 (and A beta-17) glycopeptides and to (3) compare the concentrations of these A beta glycopeptides in CSF from 20 AD patients and 20 healthy controls. Although we unambiguously identified the core 1 structures and Tyr-10 attachment sites of the glycopeptides, we did not observe any quantitative differences, determined through both peptide and oxonium ion fragments, of the desialylated A beta 1-15 or A beta 1-17 glycopeptides between the AD and non-AD group. The new quantitative glycoproteomic approach described, using double-labeled glycopeptide standards, will undoubtedly facilitate future studies of glycopeptides as clinical biomarkers but should also embrace sialylated A beta standards to reveal specific sialylation patterns of individual A beta glycopeptides in AD patients and controls.
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26.
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27.
  • Novakova, Lenka, 1984, et al. (författare)
  • Monitoring disease activity in multiple sclerosis using serum neurofilament light protein.
  • 2017
  • Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 89:22, s. 2230-2237
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.In MS, the correlation between serum and CSF NFL was r = 0.62 (p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6-32.7) ng/L to 15.7 (IQR 9.6-22.7) ng/L (p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p < 0.001) or those without new lesions on MRI (p < 0.001).Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.
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28.
  • Nováková Nyrén, Lenka, et al. (författare)
  • Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis.
  • 2017
  • Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 141:2, s. 296-304
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p<0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p=0.008, p=0.001 and p=0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.
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29.
  • Piehl, Fredrik, et al. (författare)
  • Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod
  • 2018
  • Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 24:8, s. 1046-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017, The Author(s), 2017. Background: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). Objective: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. Methods: A first cohort consisted of MS patients (n = 39) and neurological disease controls (n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort (n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). Results: Mean NFL pg/mL (standard deviation (SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated (n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod (n = 243), mean NFL pg/mL (SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10 −6 ), and levels remained stable at 24 months (13.2 (6.2)). Conclusion: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.
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30.
  • Reynolds, Chandra A, et al. (författare)
  • A survey of ABCA1 sequence variation confirms association with dementia.
  • 2009
  • Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 30:9, s. 1348-54
  • Tidskriftsartikel (refereegranskat)abstract
    • We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23-1.57, p=7.7x10(-8)). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of beta-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease.
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31.
  • Reynolds, Chandra A, et al. (författare)
  • Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.
  • 2010
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 19:10, s. 2068-2078
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted dense linkage disequilibrium mapping of a series of 25 genes putatively involved in lipid metabolism in 1567 dementia cases (including 1270 with Alzheimer disease) and 2203 Swedish controls. Across a total of 448 tested genetic markers, the strongest evidence of association was as anticipated for APOE (rs429358 at p approximately 10(-72)) followed by a previously reported association of ABCA1 (rs2230805 at p approximately 10(-8)). In the present study we report two additional markers near the SREBF1 locus on chromosome 17p that were also significant after multiple testing correction (best p=3.1 x 10(-6) for marker rs3183702). There was no convincing evidence of association for remaining genes, including candidates highlighted from recent genome-wide association studies of plasma lipids (CELSR2/PSRC1/SORT1, MLXIPL, PCSK9, GALNT2, and GCKR). The associated markers near SREBF1 reside in a large linkage disequilibrium block, extending more than 400kb across 7 candidate genes. Secondary analyses of gene expression levels of candidates spanning the LD region together with an investigation of gene network context highlighted two possible susceptibility genes including ATPAF2 and TOM1L2. Several markers in strong LD (r(2)>0.7) with rs3183702 were found to be significantly associated with AD risk in recent genome-wide association studies with similar effect sizes, providing independent support of the current findings.
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32.
  • Serenius, Fredrik, et al. (författare)
  • EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden
  • 2014
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 103:1, s. 27-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aim of this study was to investigate differences in mortality up to 1year of age in extremely preterm infants (before 27weeks) born in seven Swedish healthcare regions.Methods: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated.Results: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24weeks. Among 707 infants born alive, regional differences were found both in mortality before 12h and in the 365-day mortality rate for the subgroup (22-24weeks) and for the total group (22-26weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12h or for infants born at 25weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions.Conclusion: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.
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33.
  • Serenius, Fredrik, et al. (författare)
  • Intensity of Perinatal Care for Extremely Preterm Infants : Outcomes at 2.5 Years
  • 2015
  • Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 135:5, s. E1163-E1172
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To examine the association between intensity of perinatal care and outcome at 2.5 years' corrected age (CA) in extremely preterm (EPT) infants (<27 weeks) born in Sweden during 2004-2007. METHODS: A national prospective study in 844 fetuses who were alive at the mother's admission for delivery: 707 were live born, 137 were stillborn. Infants were assigned a perinatal activity score on the basis of the intensity of care (rates of key perinatal interventions) in the infant's region of birth. Scores were calculated separately for each gestational week (gestational age [GA]-specific scores) and for the aggregated cohort (aggregated activity scores). Primary outcomes were 1-year mortality and death or neurodevelopmental disability (NDI) at 2.5 years' CA in fetuses who were alive at the mother's admission. RESULTS: Each 5-point increment in GA-specific activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.83-0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI: 0.78-0.91) in the primary population and the 1-year mortality risk in live-born infants (aOR: 0.86; 95% CI: 0.79-0.93). In health care regions with higher aggregated activity scores, the risk of death or NDI at 2.5 years' CA was reduced in the primary population (aOR: 0.69; 95% CI: 0.50-0.96) and in live-born infants (aOR: 0.68; 95% CI: 0.48-0.95). Risk reductions were confined to the 22- to 24-week group. There was no difference in NDI risk between survivors at 2.5 years' CA. CONCLUSIONS: Proactive perinatal care decreased mortality without increasing the risk of NDI at 2.5 years' CA in EPT infants. A proactive approach based on optimistic expectations of a favorable outcome is justified.
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34.
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35.
  • Serenius, Fredrik, 1939-, et al. (författare)
  • Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.
  • 2013
  • Ingår i: Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:17, s. 1810-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. Objective To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). Design, Setting, and Participants Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. Main Outcomes and Measures Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. Results At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-III assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). Conclusions and Relevance Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth. JAMA. 2013;309(17):1810-1820
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36.
  • Serenius, Fredrik, et al. (författare)
  • Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden
  • 2013
  • Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 68:12, s. 781-783
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    •  A proactive approach to the care of extremely preterm infants has increased survival and lowered the gestational age of viability, but these improvements may be associated with later neurodevelopmental disability. EXPRESS is a national population-based prospective study of all infants born alive or stillborn at less than 27 weeks’ gestation between 2004 and 2007 in Sweden. This prospective follow-up study was undertaken to assess neurologic and developmental outcome of the EXPRESS cohort at 2.5 years corrected age compared with a matched control group born at term.Of 707 live-born infants, 497 (70%) survived to corrected age 2.5 years; the final cohort included 491 children. Each preterm child was matched with 2 control subjects at 2.5 years chronological age. Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development (Bayley III). Cerebral palsy (CP), visual and hearing disability, and a composite outcome of overall disabilities were assessed. The overall outcome was characterized as no, mild, moderate, and severe disability.Of 415 infants assessed with clinical examinations, 399, 393, and 382, respectively, completed the Bayley III cognitive, language, and motor scales; 366 control children were assessed with Bayley III. The mean composite cognitive, language, and motor scores for children in the preterm and control groups were 94 ± 12 and 104 ± 11, respectively (P < 0.001), 98 ± 17 and 109 ± 12 (P < 0.001), respectively, and 94 ± 16 and 107 ± 14 (P < 0.001), respectively. Normal cognitive development or mild cognitive disability was found in 354 preterm children (88.8%) and 364 control children (99.5%). Moderate or severe cognitive disability was present in 20 preterm children (5.0%) and 1 control child (0.3%) (P < 0.001) and in 25 (6.3%) and 1 (0.3%), respectively (P < 0.001). Normal language development or mild language disability was found in 330 children (83.9%) in the preterm group and with 351 (97.5%) in the control group (all group comparisons, P < 0.001). Normal motor development or mild motor disability occurred in 324 (84.8%) and 348 (98.6%) of children in the preterm and control groups, respectively. Moderate or severe mental developmental delay was seen in 88 and 10 children (20% and 2.8%), respectively (P < 0.001).In the preterm group, Bayley III cognitive, language, and motor scores increased with advancing gestational age at birth by 2.5 points (99% confidence interval [CI], 1.0–4.0) per week (P < 0.001), by 3.6 points (99% CI, 1.6–5.6) per week (P < 0.001), and by 2.5 points (99% CI, 0.5–4.5) per week scores (P = 0.001), respectively. Cerebral palsy was present in 32 preterm children (7.0%; 99% CI, 3.9–10.1%). Of 456 preterm children, 42.1% were classified as normal, 30.7% as having mild disabilities, and 27.2% as having moderate or severe disabilities (vs 78.1%, 18.6%, 3.3% of control subjects, respectively; P < 0.001 for all comparisons). The proportion of children with mild or no disabilities increased from 40% at 22 weeks to 83% at 26 weeks (P < 0.001 for trend). Moderate or severe disabilities decreased from 60% at 22 weeks to 17% at 26 weeks (P < 0.001 for trend).The impact of prematurity on neurodevelopmental outcome indicates that further improvements in neonatal care are necessary. Although preterm children had poorer neurodevelopmental outcomes than those born at term, 73% had no or mild disability, and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling couples facing extremely preterm birth of their infant
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37.
  • Singh Walia, Mandeep, 1987, et al. (författare)
  • Temperatures and wear at railway tread braking: Field experiments and simulations
  • 2019
  • Ingår i: Wear. - : Elsevier BV. - 0043-1648. ; 440-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Field tests were carried out for a commuter train in revenue service equipped with cast iron and organic composite brake blocks. Temperatures for wheel tread, wheel web and brake blocks and wear of wheel treads and brake blocks were recorded. The measured temperatures are used for calibrating a thermal model for assessment of wheel and block temperatures. The wear of cast iron and organic composite brake blocks is estimated using simulated temperatures and temperature-dependent wear models based on pin-on-disc experiments. It is found that a wear rate adaption factor, tentatively motivated by the presence of thermoelastic instabilities at full-scale braking that cannot be found at small-scale testing, is required for producing a simulated wear that is in agreement with results from field tests. Wheel tread wear is assessed as change in flange height for both powered and trailing wheels and for the studied train it is found that the levels of annual total wear of these types of wheels are similar in magnitude. Modelling of the tread wear originating from block–wheel contact and wheel−rail contact, combined with a comparison with measured wear magnitudes, makes it possible to quantify the wear from these two tread contacts. It is found for the powered wheels that wear induced by the wheel-rail contact and the block-wheel contact have equal importance, whereas for the trailer wheels the wear emanating from the block-wheel contact is dominating.
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38.
  • Skillbäck, Tobias, et al. (författare)
  • Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease: Results From the Swedish Mortality Registry.
  • 2014
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:4, s. 476-483
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Identifying a clinical distinction between the invariably lethal prion disease Creutzfeldt-Jakob disease (CJD) and nonprion rapidly progressive dementias is important and sometimes difficult; thus, reliable tools for diagnosis are in great demand. OBJECTIVE To test the diagnostic performance of dementia cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and the T-tau to P-tau ratio for CJD by analyzing the results from a large database of routine clinical samples in combination with diagnosis information from the Swedish Mortality Registry. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective cohort study. We cross-referenced the Swedish Mortality Registry with a data set of CSF measurements of T-tau and P-tau performed in routine clinical testing at the Clinical Neurochemistry Laboratory of the Sahlgrenska University Hospital, which serves most of Sweden. The data set consisted of 9765 deceased individuals with CSF measures, including 93 with CJD, with 52 autopsy-verified samples (56%). MAIN OUTCOMES AND MEASURES For each patient, T-tau and P-tau levels in CSF were measured and the T-tau to P-tau ratio was calculated. Biomarker levels (adjusted for age and sex) were analyzed in relation to the recorded cause of death and time of death. We specifically tested a previously defined CJD biomarker profile (T-tau >1400 ng/L and T-tau to P-tau-ratio >25). RESULTS Patients who died of CJD had elevated CSF T-tau levels and T-tau to P-tau ratio, but not elevated CSF P-tau levels, compared with patients who died of Alzheimer disease (AD) and other dementias. The previously defined biomarker profile had a specificity of 99.0%, a sensitivity of 78.5%, and a positive likelihood ratio of 79.9. When tested against common differential diagnoses, the sensitivity, specificity, and positive likelihood ratio of this profile was 78.5%, 99.6%, and 196.6, respectively, in relation to AD and 78.5%, 99.3%, and 109.3, respectively, in relation to other dementias. In CJD individuals (n=30) with repeated measurements, but not in those with AD (n=242) or other dementias (n=258), T-tau levels and T-tau to P-tau ratios increased over time. CONCLUSIONS AND RELEVANCE In this routine clinical setting, the combination of increased T-tau levels and increased T-tau to P-tau ratios in CJD patients has a very high specificity against important differential diagnoses to CJD and may serve as a clinically useful diagnostic test.
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39.
  • Sveinsson, Olafur, et al. (författare)
  • Successful combined targeting of B- and plasma cells in treatment refractory anti-NMDAR encephalitis.
  • 2017
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 312, s. 15-18
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe an extremely severe case of therapy refractory NMDA receptor encephalitis (NMDAe) in a 26-year-old woman. After rituximab, bilateral oophorectomy, repeated cycles of high dose methylprednisolone and plasma exchange, she received repeated cyclophosphamide, tocilizumab (interleukin-6 inhibitor) and finally bortezomib (plasma cell depleting drug) leading to remission after 204days in intensive care. Two years after disease onset her cognitive functions are still affected, but slowly improving and the cerebral atrophy has been partly reversed. The cerebrospinal fluid biomarker profile suggests an early synaptic/dendritic process, with subsequent neuroaxonal degeneration motivating aggressive treatment early on.
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40.
  • Teimourimanesh, Shahab, 1982, et al. (författare)
  • Tread braking of railway wheels – temperatures generated by a metro train
  • 2014
  • Ingår i: Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 228:2, s. 210-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Tread braking of railway wheels results in the kinetic energy of the train being dissipated into the wheel and blocks in the form of heat. This heat is further conducted into adjacent structures, notably the cold rail, and also transferred into the surroundings by convection and radiation. Heat partitioning between wheel and block is, for short time periods, controlled by local thermal interactions at the contact point and by the conductive properties of the bodies. However, for a metro train that performs longer periods of intermittent braking (or for drag braking) convective and radiation cooling properties of the components come into play. In the present study, results from brake rig tests and from in-field testing of a metro train are presented and used to calibrate a simulation model. It is found that the cooling level of the wheels of the metro train is substantially lower than for the wheels of a freight wagon. Moreover, it is found that the first axle on the metro train is exposed to higher cooling levels than the remaining axles. In a numerical example, temperatures of tread braked wheels are calculated using the new findings for a metro train, and the results obtained are compared with wheel temperatures as calculated assuming freight wagon conditions.
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41.
  • Thorsell, Annika, 1973, et al. (författare)
  • Proteome analysis of serum containing conditioned medium from primary astrocyte cultures
  • 2008
  • Ingår i: Journal of Proteomics & Bioinformatics. - 0974-276X. ; 1:3, s. 128-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Development of strategies that allow for identification of secreted factors in conditioned media is of significance for a wide range of research areas. Secreted factors are involved in intercellular communication and might also be biomarkers of potential clinical importance, used for early detection and diagnosis of disease. The aim of this study was to investigate whether metabolic labeling combined with mass spectrometry could be used to identify secreted proteins in serum-containing conditioned medium. Earlier proteomic studies of conditioned media have been performed on cells cultured in serum-free media. In the present study the fact that only the proteins derived from the cells contain the incorporated isotopically labeled amino acid was taken advantage of, making it possible to differentiate released proteins from medium proteins. The second objective was to examine whether any quantitative differences in the secretion profiles between primary astrocytes and astrocytes in a scratch injury model of reactive astrogliosis could be found. To our knowledge, this is the first study to identify secreted proteins in serum-containing medium using a proteomic approach involving stable isotope labeling by amino acids in cell cultures and mass spectrometry.
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42.
  • Tofiq, avin, 1996-, et al. (författare)
  • Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer's Disease : A Randomized Controlled Trial-The OmegAD Study
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:3, s. 1291-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer's disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD.OBJECTIVE: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE).METHODS: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n  =  18) or placebo (n  =  15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6.RESULTS: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable.CONCLUSION: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.
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43.
  • Torstensson, Peter, 1981-, et al. (författare)
  • Use of numerical simulation to map and mitigate railway particle emissions
  • 2019
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This feasibility study is an interdisciplinary collaboration between three research institutes (VTI, Chalmers University of Technology and RISE) and a railway brake manufacturer (Faiveley Transport Nordic). Senior researchers specialized on numerical modelling of friction brakes and on particle matters (PM), are combined with expertise in the field of train driving simulation to reduce railway’s impact on environment and human health. The train driving simulator of VTI is further developed to account for the wear generated at the brake blocks and in the wheel‒rail contact. A literature study that focuses on prediction of railway particle emissions is presented
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44.
  • Valur Dansson, Hákon, 1993, et al. (författare)
  • Predicting progression and cognitive decline in amyloid-positive patients with Alzheimer's disease
  • 2021
  • Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In Alzheimer's disease, amyloid- beta (A beta) peptides aggregate in the lowering CSF amyloid levels - a key pathological hallmark of the disease. However, lowered CSF amyloid levels may also be present in cognitively unimpaired elderly individuals. Therefore, it is of great value to explain the variance in disease progression among patients with A beta pathology. Methods A cohort of n=2293 participants, of whom n=749 were A beta positive, was selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to study heterogeneity in disease progression for individuals with A beta pathology. The analysis used baseline clinical variables including demographics, genetic markers, and neuropsychological data to predict how the cognitive ability and AD diagnosis of subjects progressed using statistical models and machine learning. Due to the relatively low prevalence of A beta pathology, models fit only to A beta-positive subjects were compared to models fit to an extended cohort including subjects without established A beta pathology, adjusting for covariate differences between the cohorts. Results A beta pathology status was determined based on the A beta(42)/A beta(40) ratio. The best predictive model of change in cognitive test scores for A beta-positive subjects at the 2-year follow-up achieved an R-2 score of 0.388 while the best model predicting adverse changes in diagnosis achieved a weighted F-1 score of 0.791. A beta-positive subjects declined faster on average than those without A beta pathology, but the specific level of CSF A beta was not predictive of progression rate. When predicting cognitive score change 4 years after baseline, the best model achieved an R-2 score of 0.325 and it was found that fitting models to the extended cohort improved performance. Moreover, using all clinical variables outperformed the best model based only on a suite of cognitive test scores which achieved an R-2 score of 0.228. Conclusion Our analysis shows that CSF levels of A beta are not strong predictors of the rate of cognitive decline in A beta-positive subjects when adjusting for other variables. Baseline assessments of cognitive function accounts for the majority of variance explained in the prediction of 2-year decline but is insufficient for achieving optimal results in longer-term predictions. Predicting changes both in cognitive test scores and in diagnosis provides multiple perspectives of the progression of potential AD subjects.
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45.
  • Walia, Mandeep Singh, 1987, et al. (författare)
  • Temperatures and wear at railway tread braking: Field experiments and simulation
  • 2018
  • Ingår i: Proceedings of the 11th International Conference on Contact Mechanics and Wear of Rail/wheel Systems, CM 2018. - 9789461869630 ; , s. 1029-1036
  • Konferensbidrag (refereegranskat)abstract
    • Field tests were carried out for a commuter train in revenue service equipped with cast iron and organic composite brake blocks. Temperatures for wheel tread, wheel web and brake blocks and wear of wheel treads and brake blocks were recorded. The measured temperatures are used for calibrating a thermal model for assessment of wheel and block temperatures. In addition, the results from thermal and wear simulations are presented. Comparisons are made between measured and simulated temperatures and wear. The wear of the cast iron brake blocks estimated using simulated temperatures and a temperature-dependent wear model calibrated from pin-on-disc experiments is in agreement with measured wear results from field tests.
  •  
46.
  • Weidung, Bodil, et al. (författare)
  • VALZ-Pilot : High-dose valacyclovir treatment in patients with early-stage Alzheimer's disease
  • 2022
  • Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Herpes simplex virus (HSV) may be involved in Alzheimer's disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication.Methods: This phase-II pilot trial involved valacyclovir administration (thrice daily, 500 mg week 1, 1000 mg weeks 2–4) to persons aged ≥ 65 years with early-stage AD, anti-HSV immunoglobulin G, and apolipoprotein E ε4. Intervention safety, tolerability, feasibility, and effects on Mini-Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarkers were evaluated.Results: Thirty-two of 33 subjects completed the trial on full dosage. Eighteen percent experienced likely intervention-related mild, temporary adverse events. CSF acyclovir concentrations were mean 5.29 ± 2.31 μmol/L. CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 concentrations increased (P = .02 and .03).Discussion: Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.
  •  
47.
  • Westman, Gabriel, 1977-, et al. (författare)
  • Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
  • 2021
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
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48.
  • Xu, Chengai, et al. (författare)
  • CSF levels of synaptosomal-associated protein 25 and synaptotagmin-1 in first-episode psychosis subjects.
  • 2020
  • Ingår i: IBRO reports. - : Elsevier BV. - 2451-8301. ; 8, s. 136-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Post-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and in vitro modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopment as a part of the schizophrenia pathophysiology. However, it is unclear to what extent synapse elimination is present during various stages of the disease, which is of clinical importance as in a real-world setting most subjects received their first-episode psychosis (FEP) diagnosis not until their mid-twenties. In the present study, we measured cerebrospinal fluid (CSF) concentrations of the two pre-synaptic proteins synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1), both of which are increased in conditions of ongoing synaptic degeneration, in 44 FEP subjects (mean age 29.9 years) and 21 healthy controls (25.9 years) using immunoprecipitation mass spectrometry. Neither protein was found to differ between healthy controls and patients, and they showed no correlation with symptom ratings, cognitive performance or antipsychotic medication. Additional studies in high-risk subjects in the early prodromal phase will be needed to address if excessive synapse destruction occurs before the development of overt psychotic symptoms.
  •  
49.
  • Öhman, Fredrik, et al. (författare)
  • Smartphone-based long-term delayed memory performance is associated with the Preclinical Alzheimer's Cognitive Composite and CSF levels of β-amyloid.
  • 2022
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:S2
  • Tidskriftsartikel (refereegranskat)abstract
    • Remote and unsupervised cognitive testing using smartphones may improve sensitivity to detect preclinical Alzheimer's disease (AD). In particular, cognitive testing at-home enables the evaluation of the potentially more sensitive long-term delayed memory retrieval, which is commonly not feasible in a clinical setting.Here, we investigated the association between remote and unsupervised smartphone-based cognitive assessments and in-clinic cognitive measurement in older participants (CDR = 0, MMSE = 29.2, age = 77). The sample (non-demented at age 70) was derived from the Swedish population-based Gothenburg H70 Birth Cohort Studies. In a subsample of participants, the retrospective correlation with cerebrospinal fluid (CSF) biomarkers analyzed at age 70 was further explored. To this point, 177 H70-participants have consented and were enrolled into the smartphone sub-study. They completed an "Object-in-Room Recall Test" (ORR) remotely and unsupervised using own mobile devices, and the recall session was initiated 24 hours after the initial learning phase. Available previously assessed CSF measures included the Aβ42/Aβ40-ratio, t-tau, p-tau, neurofilament light (NFL), and neurogranin, available in-clinic cognitive tests included the Rey Auditory Verbal Learning Test (RAVLT), Semantic Fluency, Digit-Symbol-Coding, and Mini Mental State Examination. The above-mentioned cognitive tests were used to derive the Preclinical Alzheimer's Cognitive Composite (PACC5), a composite designed to be sensitive to cognitive change in preclinical AD. All associations were examined using Pearson correlation coefficient.Preliminary analyses in a subset of participants yielded relatively strong positive correlations between PACC5 (R = .50, p<.001) and the ORR Long-term Delayed Retrieval. The strongest correlation for an individual test was observed between the RAVLT Delayed Retrieval and the ORR Long-term Delayed Retrieval (R = .52, p<.001). Regarding the CSF biomarkers, Aβ42/Aβ40-ratio at age 70 was positively correlated with the ORR Long-term Delayed Retrieval at age 77 (R = .43, p<.01), while measures of t-tau, p-tau, NFL, and neurogranin at age 70 were not.Our findings demonstrate the potential of smartphone-based cognitive assessment to detect features of preclinical AD in a population-based sample of older adults. Future analyses will address the relationship between these novel cognitive measures in relation to longitudinal CSF- and neuroimaging-based biomarkers and clinical progression.
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