330 results on '"Selnes, P."'
Search Results
2. Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease
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Fernando Gonzalez-Ortiz, Bjørn-Eivind Kirsebom, José Contador, Jordan E. Tanley, Per Selnes, Berglind Gísladóttir, Lene Pålhaugen, Mathilde Suhr Hemminghyth, Jonas Jarholm, Ragnhild Skogseth, Geir Bråthen, Gøril Grøndtvedt, Atle Bjørnerud, Sandra Tecelao, Knut Waterloo, Dag Aarsland, Aida Fernández-Lebrero, Greta García-Escobar, Irene Navalpotro-Gómez, Michael Turton, Agnes Hesthamar, Przemyslaw R. Kac, Johanna Nilsson, Jose Luchsinger, Kathleen M. Hayden, Peter Harrison, Albert Puig-Pijoan, Henrik Zetterberg, Timothy M. Hughes, Marc Suárez-Calvet, Thomas K. Karikari, Tormod Fladby, and Kaj Blennow
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Science - Abstract
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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- 2024
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3. Segmenting white matter hyperintensities on isotropic three-dimensional Fluid Attenuated Inversion Recovery magnetic resonance images: Assessing deep learning tools on norwegian imaging database
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Røvang, Martin Soria, Selnes, Per, MacIntosh, Bradley John, Groote, Inge Rasmus, Paalhaugen, Lene, Carole, Sudre, Fladby, Tormod, and Bjørnerud, Atle
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Electrical Engineering and Systems Science - Image and Video Processing ,Computer Science - Computer Vision and Pattern Recognition - Abstract
Automated segmentation of white matter hyperintensities (WMHs) is an essential step in neuroimaging analysis of Magnetic Resonance Imaging (MRI). Fluid Attenuated Inversion Recovery (FLAIR-weighted) is an MRI contrast that is particularly useful to visualize and quantify WMHs, a hallmark of cerebral small vessel disease and Alzheimer's disease (AD). Clinical MRI protocols migrate to a three-dimensional (3D) FLAIR-weighted acquisition to enable high spatial resolution in all three voxel dimensions. The current study details the deployment of deep learning tools to enable automated WMH segmentation and characterization from 3D FLAIR-weighted images acquired as part of a national AD imaging initiative. Among 441 participants (194 male, mean age: (64.91 +/- 9.32) years) from the DDI study, two in-house networks were trained and validated across five national collection sites. Three models were tested on a held-out subset of the internal data from the 441 participants and an external dataset with 29 cases from an international collaborator. These test sets were evaluated independently. Five established WMH performance metrics were used for comparison against ground truth human-in-the-loop segmentation. Results of the three networks tested, the 3D nnU-Net had the best performance with an average dice similarity coefficient score of 0.76 +/- 0.16, performing better than both the in-house developed 2.5D model and the SOTA Deep Bayesian network. With the increasing use of 3D FLAIR-weighted images in MRI protocols, our results suggest that WMH segmentation models can be trained on 3D data and yield WMH segmentation performance that is comparable to or better than state-of-the-art without the need for including T1-weighted image series., Comment: 20 Pages, 9 Figures, 2 Tables
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- 2022
4. An overview of emerging smart capsules using other-than-light technologies for colonic disease detection
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Gohar Jalayeri Nia, Ola Selnes, Pablo Cortegoso Valdivia, and Anastasios Koulaouzidis
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Wireless capsule endoscopy (CE) has revolutionized gastrointestinal diagnostics, offering a non-invasive means to visualize and monitor the GI tract. This review traces the evolution of CE technology. Addressing the limitations of traditional white light (WL) CE, the paper explores non-WL technologies, integrating diverse sensing modalities and novel biomarkers to enhance diagnostic capabilities. Concluding with an assessment of Technology Readiness Levels, the paper emphasizes the transformative impact of non-WL colon CE devices on GI diagnostics, promising more precise, patient-centric, and accessible healthcare for GI disorders.
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- 2024
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5. Retention of endoscopic capsules in diverticula: Literature review of a capsule endoscopy rarity
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Camilla Thorndal, Ola Selnes, Ian Io Lei, Sebastian Schostek, and Anastasios Koulaouzidis
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Endoscopy Small Bowel ,Capsule endoscopy ,Endoscopy Upper GI Tract ,Endoscopy Lower GI Tract ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2024
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6. Depressive symptoms are not associated with predementia CSF amyloid pathology
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Cecilia Magdalena Eriksson, Bjørn-Eivind Kirsebom, Ragna Espenes, Nikias Siafarikas, Knut Waterloo, Arvid Rongve, Per Selnes, Dag Aarsland, Tormod Fladby, and Erik Hessen
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Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
ABSTRACT INTRODUCTION: Depressive symptoms are associated with Alzheimer’s disease (AD), but their neurobiological and neuropsychological correlates remain poorly understood. We investigate if depressive symptoms are associated with amyloid (Aβ) pathology and cognition in predementia AD. METHODS: We included Subjective Cognitive Decline (SCD, n= 160) and Mild Cognitive Impairment (MCI, n=192) from the Dementia Disease Initiation cohort. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Aβ pathology was determined using cerebrospinal fluid (CSF) Aβ42/40 ratio. Associations between depressive symptoms and cognition were assessed with logistic regression. RESULTS: Only the Aβ negative MCI group (MCI-Aβ-) was associated with depressive symptoms (OR=2.65, p=.005). Depressive symptoms were associated with worse memory in MCI-Aβ- (OR=0.94, p=.039), but with better performance in MCI-Aβ+ (OR=1.103, p=.001). DISCUSSION: Our results suggest that depressive symptoms in MCI are neither associated with Aβ pathology, nor AD-associated memory impairment. However, memory impairment in non-AD MCI may relate to depressive symptoms.
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- 2024
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7. Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer’s disease
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Kaja Nordengen, Bjørn-Eivind Kirsebom, Grit Richter, Lene Pålhaugen, Berglind Gísladóttir, Nikias Siafarikas, Arne Nakling, Arvid Rongve, Geir Bråthen, Gøril Rolfseng Grøntvedt, Fernando Gonzalez, Knut Waterloo, Kulbhushan Sharma, Thomas Karikari, Eleonora M. Vromen, Betty M. Tijms, Pieter J. Visser, Per Selnes, Milicia G. Kramberger, Bengt Winblad, Kaj Blennow, and Tormod Fladby
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Inflammation ,Biomarkers ,Cerebrospinal fluid ,Alzheimer’s disease ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background 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. Methods 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 6 years from baseline (mean 2.8 years). 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. Results Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p
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- 2023
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8. Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer’s disease
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Nordengen, Kaja, Kirsebom, Bjørn-Eivind, Richter, Grit, Pålhaugen, Lene, Gísladóttir, Berglind, Siafarikas, Nikias, Nakling, Arne, Rongve, Arvid, Bråthen, Geir, Grøntvedt, Gøril Rolfseng, Gonzalez, Fernando, Waterloo, Knut, Sharma, Kulbhushan, Karikari, Thomas, Vromen, Eleonora M., Tijms, Betty M., Visser, Pieter J., Selnes, Per, Kramberger, Milicia G., Winblad, Bengt, Blennow, Kaj, and Fladby, Tormod
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- 2023
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9. Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol
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Catherine Morgan, Frederik Barkhof, David L Thomas, Saima Hilal, Moritz Brandt, Betty M Tijms, Majon Muller, Tormod Fladby, Jennifer Linn, Per Selnes, Atle Bjørnerud, Elsmarieke M van de Giessen, Beatriz Padrela, Amnah Mahroo, Mervin Tee, Markus H Sneve, Paulien Moyaert, Oliver Geier, Joost P A Kuijer, Soetkin Beun, Wibeke Nordhøy, Yufei David Zhu, Mareike A Buck, Daniel C Hoinkiss, Simon Konstandin, Jörn Huber, Julia Wiersinga, Roos Rikken, Diederick de Leeuw, Håkon Grydeland, Lynette Tippett, Erin E Cawston, Esin Ozturk-Isik, Anders Fjell, Kristine Walhovd, Lene Pålhaugen, Patricia Clement, Eric Achten, Udunna Anazodo, Klaus Eickel, Jan Petr, Matthias Günther, and Henk J M M Mutsaerts
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Medicine - Abstract
Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
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- 2024
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10. Comparative analysis of multimodal biomarkers for amyloid-beta positivity detection in Alzheimer's disease cohorts
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Mostafa Mehdipour Ghazi, Per Selnes, Santiago Timón-Reina, Sandra Tecelão, Silvia Ingala, Atle Bjørnerud, Bjørn-Eivind Kirsebom, Tormod Fladby, and Mads Nielsen
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Alzheimer's disease ,amyloid-beta ,magnetic resonance imaging ,deep machine learning ,biomarker classification ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionEfforts to develop cost-effective approaches for detecting amyloid pathology in Alzheimer's disease (AD) have gained significant momentum with a focus on biomarker classification. Recent research has explored non-invasive and readily accessible biomarkers, including magnetic resonance imaging (MRI) biomarkers and some AD risk factors.MethodsIn this comprehensive study, we leveraged a diverse dataset, encompassing participants with varying cognitive statuses from multiple sources, including cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and our in-house Dementia Disease Initiation (DDI) cohort. As brain amyloid plaques have been proposed as sufficient for AD diagnosis, our primary aim was to assess the effectiveness of multimodal biomarkers in identifying amyloid plaques, using deep machine learning methodologies.ResultsOur findings underscore the robustness of the utilized methods in detecting amyloid beta positivity across multiple cohorts. Additionally, we investigated the potential of demographic data to enhance MRI-based amyloid detection. Notably, the inclusion of demographic risk factors significantly improved our models' ability to detect amyloid-beta positivity, particularly in early-stage cases, exemplified by an average area under the ROC curve of 0.836 in the unimpaired DDI cohort.DiscussionThese promising, non-invasive, and cost-effective predictors of MRI biomarkers and demographic variables hold the potential for further refinement through considerations like APOE genotype and plasma markers.
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- 2024
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11. Peak width of skeletonized mean diffusivity as a biomarker of small vessel disease in predementia Alzheimer's disease
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Jonas Jarholm, Sandra Tecelão, Lene Pålhaugen, Atle Bjørnerud, Bjørn Eivind Kirsebom, Tormod Fladby, and Per Selnes
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Specialties of internal medicine ,RC581-951 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: Alzheimer's disease (AD) and cerebral small vessel disease (SVD) frequently coexist, and increasing evidence suggest that microvascular changes may be related to AD pathology. SVD is however heterogeneously expressed on magnetic resonance imaging (MRI), and several novel methods can determine different aspects of vascular pathology. These methods need to be explored properly in clinical AD cohorts to better understand the link between AD and SVD, and could possibly be included in the staging and diagnostics of AD. Methods: 588 subjects were included from the Norwegian Dementia Disease initiation (DDI) cohort, longitudinal data was available for 285 subjects. Subjects underwent clinical examination including lumbar puncture, and were classified according to the A/T/N-system into the following groups: A-/T-/N- (N=208), A-/T+/N± (N=11), A+/T-/N- (N=75)and A+/T+/N±(N=157) according to positive (+) or negative (-) values of cerebrospinal fluid (CSF) amyloid-β42/40-ratio (A), phosphorylated-tau (T) and total-tau (N)). We used Peak width of skeletonized mean diffusivity (PSMD), a novel MRI Diffusion Tensor Imaging (DTI) method for determination of global SVD-burden based on an automated algorithm (5). We used a mixed linear regression model to determine baseline and longitudinal differences in PSMD across A/T/N-classified subjects in a predementia cohort, adjusted for subject and scanner as a random effect. Results: Compared to A-/T-/N- at baseline, we found significantly larger SVD burden in A+/T-/N- compared to A-/T-/N- (p
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- 2024
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12. Association between angiogenic factors and vascular risk, white matter hyperintensities and CSF amyloid beta
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Lene Pålhaugen, Berglind Gísladóttir, Jonas Alexander Jarholm, Bjørn-Eivind Kirsebom, Per Selnes, and Tormod Fladby
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Specialties of internal medicine ,RC581-951 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: Angiogenic mediators like placental growth factor (PlGF) and vascular endothelial growth factors (VEFG-C and VEFG-A) in cerebrospinal fluid (CSF) are suggested markers of cerebral small vessel disease (SVD). SVD is a cause of vascular cognitive impairment and dementia (VCID), but studies have shown that both non-amyloid SVD related to vascular risk factors and cerebral amyloid angiopathy (CAA) often exist in patients with Alzheimer's Disease (AD). CSF amyloid beta (Abeta) 42 is reduced in AD due to trapping in parenchymal plaques. Abeta40 is mainly deposited in the vasculature, and low CSF concentrations are seen in CAA. In this cross-sectional study, we examine the associations between these angiogenic factors, vascular risk and white matter hyperintensities (WMH) on MRI, as well as Abeta peptides in CSF. Methods: We recruited non-demented participants from the Norwegian Dementia Disease Initiation cohort. We measured PlGF, VEGF-C and VEGF-A in CSF. Vascular risk was assessed with the Framingham Risk Score (FRS) for cardiovascular disease. WMH volumes were calculated by an automated algorithm. We used linear regression to examine associations between angiogenic markers and FRS, CSF levels of Abeta42 and Abeta40. Associations with WMH load were assessed in models without (Model 1) and with (Model 2) correction for amyloid status. Continuous variables were standardized. Age and sex were covariates. Results: In total, 240 individuals (mean age 63.4 years, 128 female/112 male, 124 cognitively normal/116 cognitively impaired) were included. Reduced VEGF-C was associated with higher FRS (B=-0.292, p
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- 2024
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13. DEveloping BBB-ASL as non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD): Study design
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Beatriz Padrela, Amnah Mahroo, Mervin Tee, Markus Sneve, Paulien Moyaert, Oliver Geier, Joost Kuijer, Soetkin Beun, Wibeke Nordhøy, Yufei David Zhu, Mareike Buck, Daniel Hoinkiss, Simon Konstandin, Jörn Huber, Julia Wiersinga, Roos Rikken, Diederick de Leeuw, Håkon Grydeland, Lynette Tippett, Erin Cawston, Esin Ozturk-Isik, Jennifer Linn, Moritz Brandt, Betty Tijms, Elsmarieke van de Giessen, Majon Muller, Anders Fjell, Kristine Walhovd, Lene Pålhaugen, Per Selnes, Patricia Clement, Eric Achten, Udunna Anazodo, Frederik Barkhof, Saima Hilal, Tormod Fladby, Klaus Eickel, Catherine Morgan, David Thomas, Jan Petr, Matthias Günther, and Henk J.M.M. Mutsaerts
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Specialties of internal medicine ,RC581-951 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker. Methods: DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1). Expected Results: Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites. Discussion: The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.
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- 2024
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14. Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
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Jansen, Iris E., van der Lee, Sven J., Gomez-Fonseca, Duber, de Rojas, Itziar, Dalmasso, Maria Carolina, Grenier-Boley, Benjamin, Zettergren, Anna, Mishra, Aniket, Ali, Muhammad, Andrade, Victor, Bellenguez, Céline, Kleineidam, Luca, Küçükali, Fahri, Sung, Yun Ju, Tesí, Niccolo, Vromen, Ellen M., Wightman, Douglas P., Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Amouyel, Philippe, Athanasiu, Lavinia, Bahrami, Shahram, Bailly, Henri, Belbin, Olivia, Bergh, Sverre, Bertram, Lars, Biessels, Geert Jan, Blennow, Kaj, Blesa, Rafael, Boada, Mercè, Boland, Anne, Buerger, Katharina, Carracedo, Ángel, Cervera-Carles, Laura, Chene, Geneviève, Claassen, Jurgen A. H. R., Debette, Stephanie, Deleuze, Jean-Francois, de Deyn, Peter Paul, Diehl-Schmid, Janine, Djurovic, Srdjan, Dols-Icardo, Oriol, Dufouil, Carole, Duron, Emmanuelle, Düzel, Emrah, Fladby, Tormod, Fortea, Juan, Frölich, Lutz, García-González, Pablo, Garcia-Martinez, Maria, Giegling, Ina, Goldhardt, Oliver, Gobom, Johan, Grimmer, Timo, Haapasalo, Annakaisa, Hampel, Harald, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herukka, Sanna-Kaisa, Holstege, Henne, Jarholm, Jonas, Kern, Silke, Knapskog, Anne-Brita, Koivisto, Anne M., Kornhuber, Johannes, Kuulasmaa, Teemu, Lage, Carmen, Laske, Christoph, Leinonen, Ville, Lewczuk, Piotr, Lleó, Alberto, de Munain, Adolfo López, Lopez-Garcia, Sara, Maier, Wolfgang, Marquié, Marta, Mol, Merel O., Montrreal, Laura, Moreno, Fermin, Moreno-Grau, Sonia, Nicolas, Gael, Nöthen, Markus M., Orellana, Adelina, Pålhaugen, Lene, Papma, Janne M., Pasquier, Florence, Perneczky, Robert, Peters, Oliver, Pijnenburg, Yolande A. L., Popp, Julius, Posthuma, Danielle, Pozueta, Ana, Priller, Josef, Puerta, Raquel, Quintela, Inés, Ramakers, Inez, Rodriguez-Rodriguez, Eloy, Rujescu, Dan, Saltvedt, Ingvild, Sanchez-Juan, Pascual, Scheltens, Philip, Scherbaum, Norbert, Schmid, Matthias, Schneider, Anja, Selbæk, Geir, Selnes, Per, Shadrin, Alexey, Skoog, Ingmar, Soininen, Hilkka, Tárraga, Lluís, Teipel, Stefan, Tijms, Betty, Tsolaki, Magda, Van Broeckhoven, Christine, Van Dongen, Jasper, van Swieten, John C., Vandenberghe, Rik, Vidal, Jean-Sébastien, Visser, Pieter J., Vogelgsang, Jonathan, Waern, Margda, Wagner, Michael, Wiltfang, Jens, Wittens, Mandy M. J., Zetterberg, Henrik, Zulaica, Miren, van Duijn, Cornelia M., Bjerke, Maria, Engelborghs, Sebastiaan, Jessen, Frank, Teunissen, Charlotte E., Pastor, Pau, Hiltunen, Mikko, Ingelsson, Martin, Andreassen, Ole A., Clarimón, Jordi, Sleegers, Kristel, Ruiz, Agustín, Ramirez, Alfredo, Cruchaga, Carlos, Lambert, Jean-Charles, and van der Flier, Wiesje
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- 2022
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15. Exploring the Potential of Atlantic Mesopelagic Species Processed on Board Commercial Fishing Vessels as a Source of Dietary Lipids
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Maria A. Madina, Eduardo Grimaldo, Leif Grimsmo, Bendik Toldnes, Rasa Slizyte, Ana Karina Carvajal, Marte Schei, Merethe Selnes, and Eva Falch
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marine oils ,omega-3 ,EPA ,DHA ,thermal separation ,hydrolysis ,Chemical technology ,TP1-1185 - Abstract
This study investigates the use of untapped mesopelagic species as a source of long-chain polyunsaturated omega-3 fatty acids (LC n-3 PUFAs) to meet the growing demand. The challenges faced by commercial fishing vessels, such as varying catch rates and species distribution affecting lipid levels, are addressed. Marine oils were produced post-catch using thermal separation and enzymatic hydrolysis during four commercial cruises, screening approximately 20,000 kg of mixed mesopelagic species. Maurolicus muelleri and Benthosema glaciale were the dominant species in the catch, while krill was the primary bycatch. The lipid composition varied, with B. glaciale having a higher prevalence of wax esters, while triacylglycerols and phospholipids were more predominant in the other species. LC n-3 PUFAs ranged from 19% to 44% of lipids, with an average EPA + DHA content of 202 mg/g of oil. Both processing methods achieved oil recoveries of over 90%. Estimates indicate that the mesopelagic biomass in the Northeast Atlantic could supply annual recommended levels of EPA + DHA to 1.5 million people, promoting healthy heart and brain functions. These findings offer valuable insights for considering mesopelagic species as a potential source of dietary marine lipids, laying the groundwork for further research and innovation in processing and obtaining valuable compounds from such species.
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- 2024
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16. Conference Report: The FutuRE oF MinimalLy InvasivE GI and Capsule DiagnosTics (REFLECT) Nyborg, Denmark, October 2023
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Ola Selnes, Camilla Thorndal, Lea Østergaard Hansen, Sebastian Radic Eskemose, and Anastasios Koulaouzidis
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n/a ,Medicine (General) ,R5-920 - Abstract
The gastrointestinal (GI) tract, particularly the small bowel (SB), can be challenging for novel investigation tools [...]
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- 2024
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17. Radiological features of brain hemorrhage through automated segmentation from computed tomography in stroke and traumatic brain injury
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Bradley J. MacIntosh, Qinghui Liu, Till Schellhorn, Mona K. Beyer, Inge Rasmus Groote, Pål C. Morberg, Joshua M. Poulin, Maiken N. Selseth, Ragnhild C. Bakke, Aina Naqvi, Amir Hillal, Teresa Ullberg, Johan Wassélius, Ole M. Rønning, Per Selnes, Espen S. Kristoffersen, Kyrre Eeg Emblem, Karoline Skogen, Else C. Sandset, and Atle Bjørnerud
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computed tomography ,intracerebral hemorrhage ,stroke ,traumatic brain injury ,segmentation ,deep learning ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionRadiological assessment is necessary to diagnose spontaneous intracerebral hemorrhage (ICH) and traumatic brain injury intracranial hemorrhage (TBI-bleed). Artificial intelligence (AI) deep learning tools provide a means for decision support. This study evaluates the hemorrhage segmentations produced from three-dimensional deep learning AI model that was developed using non-contrast computed tomography (CT) imaging data external to the current study.MethodsNon-contrast CT imaging data from 1263 patients were accessed across seven data sources (referred to as sites) in Norway and Sweden. Patients were included based on ICH, TBI-bleed, or mild TBI diagnosis. Initial non-contrast CT images were available for all participants. Hemorrhage location frequency maps were generated. The number of estimated haematoma clusters was correlated with the total haematoma volume. Ground truth expert annotations were available for one ICH site; hence, a comparison was made with the estimated haematoma volumes. Segmentation volume estimates were used in a receiver operator characteristics (ROC) analysis for all samples (i.e., bleed detected) and then specifically for one site with few TBI-bleed cases.ResultsThe hemorrhage frequency maps showed spatial patterns of estimated lesions consistent with ICH or TBI-bleed presentations. There was a positive correlation between the estimated number of clusters and total haematoma volume for each site (correlation range: 0.45–0.74; each p-value < 0.01) and evidence of ICH between-site differences. Relative to hand-drawn annotations for one ICH site, the VIOLA-AI segmentation mask achieved a median Dice Similarity Coefficient of 0.82 (interquartile range: 0.78 and 0.83), resulting in a small overestimate in the haematoma volume by a median of 0.47 mL (interquartile range: 0.04 and 1.75 mL). The bleed detection ROC analysis for the whole sample gave a high area-under-the-curve (AUC) of 0.92 (with sensitivity and specificity of 83.28% and 95.41%); however, when considering only the mild head injury site, the TBI-bleed detection gave an AUC of 0.70.DiscussionAn open-source segmentation tool was used to visualize hemorrhage locations across multiple data sources and revealed quantitative hemorrhage site differences. The automated total hemorrhage volume estimate correlated with a per-participant hemorrhage cluster count. ROC results were moderate-to-high. The VIOLA-AI tool had promising results and might be useful for various types of intracranial hemorrhage.
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- 2023
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18. The effect of an integrated care intervention of multidisciplinary mental health treatment and employment services for trauma-affected refugees: study protocol for a randomised controlled trial
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Maja Bruhn, Henriette Laugesen, Matilde Kromann-Larsen, Cathrine Selnes Trevino, Lene Eplov, Carsten Hjorthøj, and Jessica Carlsson
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Refugee ,Trauma ,Post-traumatic stress disorder ,PTSD ,Cross-sectoral ,Integrated care ,Medicine (General) ,R5-920 - Abstract
Abstract Background The complexity of past trauma and ongoing post-migration stressors challenges the existing mental health treatment for trauma-affected refugees. Therefore, interventions are needed to accommodate these complex challenges in mental health treatment. This study examines the effect of an add-on integrated care intervention compared to treatment as usual (TAU) for trauma-affected refugees in a randomised controlled trial (RCT). Methods The study is carried out at a Danish outpatient clinic and will include 197 treatment-seeking refugees with post-traumatic stress disorder (PTSD) who are unemployed and affiliated with municipal employment services. Mental health TAU comprises 10 sessions with a medical doctor (pharmacological treatment and psychoeducation) and 16–20 sessions with a psychologist (manual-based cognitive behavioural therapy) for a period of 8 to 12 months. The add-on intervention strengthens coordination between mental health treatment and employment interventions with three cross-sectoral collaborative meetings during the mental health treatment. The integrated care intervention draws attention to the bidirectional impact of mental health problems and post-migration stressors and focuses on cross-sectoral shared plans. The primary outcome is functioning, measured by WHODAS 2.0, the interviewer-administered 12-item version, with secondary outcomes measuring quality of life, mental health symptoms, and post-migration stressors. Discussion The RCT is novel in intervention design for trauma-affected refugees and will bring forward new perspectives and knowledge of integrated care interventions for trauma-affected refugees. The integrated care intervention is expected to reduce post-migration stressors that negatively affect the treatment of trauma-related mental health problems, thereby improving preconditions for enhanced treatment outcomes. The intervention builds on existing practices in the Danish healthcare and employment sectors, which ensures high scalability and sustainability for future practices. Trial registration ClinicalTrials.gov Identifier: NCT04244864 , registered 28 January 2020. Protocol version: 17 September 2022, version 2.
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- 2022
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19. The ANeED study – ambroxol in new and early dementia with Lewy bodies (DLB): protocol for a phase IIa multicentre, randomised, double-blinded and placebo-controlled trial
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Luiza Jadwiga Chwiszczuk, Monica Haraldseid Breitve, Bjørn-Eivind Bordewick Kirsebom, Per Selnes, John Chr. Fløvig, Anne-Brita Knapskog, Ragnhild E. Skogseth, Jessica Hubbers, Elin Holst-Larsen, and Arvid Rongve
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DLB ,dementia with Lewy bodies (DLB) ,ambroxol ,treatment ,clinical trial in DLB ,alpha-synuclein ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
BackgroundCurrently, there are no disease-modifying pharmacological treatment options for dementia with Lewy bodies (DLB). The hallmark of DLB is pathological alpha-synuclein (aS) deposition. There are growing amounts of data suggesting that reduced aS clearance is caused by failure in endolysosomal and authophagic pathways, as well as and glucocerebrosidase (GCase) dysfunction and mutations in the GCase gene (GBA). The population’s studies demonstrated that the incidence of GBA mutations is higher among Parkinson’s disease (PD) patients, and carriers of such mutations have a higher risk of developing PD. The incidence of GBA mutations is even higher in DLB and a genome-wide association study (GWAS) confirmed the correlation between GBA mutations and DLB. In vivo experiments have shown that ambroxol (ABX) may increase GCase activity and GCase levels and therefore enhance aS autophagy-lysosome degradation pathways. Moreover, there is an emerging hypothesis that ABX may have an effect as a DLB modifying drug. The aims of the study “Ambroxol in new and early Dementia with Lewy Bodies (ANeED) are to investigate the tolerability, safety and effects of ABX in patients with DLB.MethodsThis is a multicentre, phase IIa, double-blinded, randomised and placebo-controlled clinical trial, using a parallel arm design for 18 months’ follow-up. The allocation ratio is 1:1 (treatment:placebo).DiscussionThe ANeED study is an ongoing clinical drug trial with ABX. The unique, but not fully understood mechanism of ABX on the enhancement of lysosomal aS clearance may be promising as a possible modifying treatment in DLB.Trial RegistrationThe clinical trial is registered in the international trials register – clinicaltrials.com (NCT0458825) and nationally at the Current Research Information System in Norway (CRISTIN 2235504).
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- 2023
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20. The effect of an integrated care intervention of multidisciplinary mental health treatment and employment services for trauma-affected refugees: study protocol for a randomised controlled trial
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Bruhn, Maja, Laugesen, Henriette, Kromann-Larsen, Matilde, Trevino, Cathrine Selnes, Eplov, Lene, Hjorthøj, Carsten, and Carlsson, Jessica
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- 2022
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21. CSF, Blood, and MRI Biomarkers in Skogholt’s Disease—A Rare Neurodegenerative Disease in a Norwegian Kindred
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Klaus Thanke Aspli, Jan O. Aaseth, Trygve Holmøy, Kaj Blennow, Henrik Zetterberg, Bjørn-Eivind Kirsebom, Tormod Fladby, and Per Selnes
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tau protein ,amyloid beta ,PDGFRβ ,β-trace protein ,NFL ,GFAP ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Skogholt’s disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein have been confirmed, and recently, very high concentrations of CSF total and phosphorylated tau have been detected in Skogholt patients. The symptoms and observed biomarker changes in Skogholt’s disease are largely nonspecific, and further studies are necessary to elucidate the disease mechanisms. Here, we report the results of neurochemical analyses of plasma and CSF, as well as results from the morphometric segmentation of cerebral magnetic resonance imaging. We analyzed the biomarkers Aβ1––42, Aβ1–40, Aβx–38, Aβx–40, Aβx–42, total and phosphorylated tau, glial fibrillary acidic protein, neurofilament light chain, platelet-derived growth factor receptor beta, and beta-trace protein. All analyzed CSF biomarkers, except neurofilament light chain and Aβ1/x–42, were increased several-fold. In blood, none of these biomarkers were significantly different between the Skogholt and control groups. MRI volumetric segmentation revealed decreases in the ventricular, white matter, and choroid plexus volumes in the Skogholt group, with an accompanying increase in white matter lesions. The cortical thickness and subcortical gray matter volumes were increased in the Skogholt group. Pathophysiological changes resulting from choroidal dysfunction and/or abnormal CSF turnover, which may cause the increases in CSF protein and brain biomarker levels, are discussed.
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- 2023
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22. Segmenting white matter hyperintensities on isotropic three-dimensional Fluid Attenuated Inversion Recovery magnetic resonance images: Assessing deep learning tools on a Norwegian imaging database.
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Martin Soria Røvang, Per Selnes, Bradley J MacIntosh, Inge Rasmus Groote, Lene Pålhaugen, Carole Sudre, Tormod Fladby, and Atle Bjørnerud
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Medicine ,Science - Abstract
An important step in the analysis of magnetic resonance imaging (MRI) data for neuroimaging is the automated segmentation of white matter hyperintensities (WMHs). Fluid Attenuated Inversion Recovery (FLAIR-weighted) is an MRI contrast that is particularly useful to visualize and quantify WMHs, a hallmark of cerebral small vessel disease and Alzheimer's disease (AD). In order to achieve high spatial resolution in each of the three voxel dimensions, clinical MRI protocols are evolving to a three-dimensional (3D) FLAIR-weighted acquisition. The current study details the deployment of deep learning tools to enable automated WMH segmentation and characterization from 3D FLAIR-weighted images acquired as part of a national AD imaging initiative. Based on data from the ongoing Norwegian Disease Dementia Initiation (DDI) multicenter study, two 3D models-one off-the-shelf from the NVIDIA nnU-Net framework and the other internally developed-were trained, validated, and tested. A third cutting-edge Deep Bayesian network model (HyperMapp3r) was implemented without any de-novo tuning to serve as a comparison architecture. The 2.5D in-house developed and 3D nnU-Net models were trained and validated in-house across five national collection sites among 441 participants from the DDI study, of whom 194 were men and whose average age was (64.91 +/- 9.32) years. Both an external dataset with 29 cases from a global collaborator and a held-out subset of the internal data from the 441 participants were used to test all three models. These test sets were evaluated independently. The ground truth human-in-the-loop segmentation was compared against five established WMH performance metrics. The 3D nnU-Net had the highest performance out of the three tested networks, outperforming both the internally developed 2.5D model and the SOTA Deep Bayesian network with an average dice similarity coefficient score of 0.76 +/- 0.16. Our findings demonstrate that WMH segmentation models can achieve high performance when trained exclusively on FLAIR input volumes that are 3D volumetric acquisitions. Single image input models are desirable for ease of deployment, as reflected in the current embedded clinical research project. The 3D nnU-Net had the highest performance, which suggests a way forward for our need to automate WMH segmentation while also evaluating performance metrics during on-going data collection and model retraining.
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- 2023
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23. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
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Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle
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- 2021
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24. Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) – a national research and quality registry with a biomaterial collection
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Anne-Brita Knapskog, Mala Naik, Ingvild Saltvedt, Anette Hylen Ranhoff, Knut Engedal, Geir Selbaek, Sverre Bergh, Ingrid Tøndel Medbøen, Karin Persson, Marit Nåvik, Torunn Holm Totland, Cathrine Selnes Treviño, Ingun Ulstein, Anne Brækhus, Anne Rita Øksengård, Peter Otto Horndalsveen, Anne Liv Lyngroth, Dagny Bekkeheien Skrettingland, Jelena Zugic Soares, and Bente Johnsen
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Medicine - Abstract
Purpose The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data.Participants The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009–2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders.Findings to date All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources.Future plans The finish date of NorCog was originally in 2029. In 2021, the registry’s legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.
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- 2022
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25. Blood pressure trajectories over 35 years and dementia risk: A retrospective study: The HUNT study
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Geir Selbaek, Josephine Stuebs, Knut Engedal, Vladimir Hachinski, Knut Hestad, Cathrine Selnes Trevino, Håvard Skjellegrind, Yehani Wedatilake, and Bjørn Heine Strand
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blood pressure ,dementia ,trajectory ,cohort study ,Alzheimer ,vascular dementia ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
High blood pressure is a well-established risk factor of dementia. However, the timing of the risk remains controversial. The aim of the present study was to compare trajectories of systolic blood pressure (SBP) over a 35-year follow-up period in the Health Survey in Trøndelag (HUNT) from study wave 1 to 4 in people with and without a dementia diagnosis at wave 4 (HUNT4). This is a retrospective cohort study of participants aged ≥ 70 years in HUNT4, where 9,720 participants were assessed for dementia. In the HUNT study all residents aged ≥ 20 years have been invited to four surveys: HUNT1 1984–86, HUNT2 1995–97, HUNT3 2006–08 and HUNT4 2017–19. The study sample was aged 70–102 years (mean 77.6, SD 6.0) at HUNT4, 54% were women and 15.5% had dementia, 8.8% had Alzheimer’s disease (AD), 1.6% had vascular dementia (VaD) and 5.1% had other types of dementia. Compared to those without dementia at HUNT4, those with dementia at HUNT4 had higher SBP at HUNT1 and HUNT2, but lower SBP at HUNT4. These differences at HUNT1 and 2 were especially pronounced among women. Results did not differ across birth cohorts. For dementia subtypes at HUNT4, the VaD group had a higher SBP than the AD group at HUNT2 and 3. Age trajectories in SBP showed that the dementia group experienced a steady increase in SBP until 65 years of age and a decrease from 70 to 90 years. SBP in the no- dementia group increased until 80 years before it leveled off from 80 to 90 years. The present study confirms findings of higher midlife SBP and lower late-life SBP in people with dementia. This pattern may have several explanations and it highlights the need for close monitoring of BP treatment in older adults, with frequent reappraisal of treatment needs.
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- 2022
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26. Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol
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Padrela, B., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., David Zhu, Y., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B. M., Giessen, E. M., Muller, M., Fjell, A., Walhovd, K., Bjørnerud, A., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., Mutsaerts, H. J. M. M., Padrela, B., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., David Zhu, Y., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B. M., Giessen, E. M., Muller, M., Fjell, A., Walhovd, K., Bjørnerud, A., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., and Mutsaerts, H. J. M. M.
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Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and ADrelated pathologies. Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
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- 2024
27. Community paramedicine: cost–benefit analysis and safety evaluation in paramedical emergency services in rural areas – a scoping review
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Hege Selnes Haugdahl, Marianne Lysne, Odd Eirik Elden, and Oddvar Uleberg
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Medicine - Published
- 2022
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28. Prospects for upgrading by the European kelp sector
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van den Burg, Sander, Selnes, Trond, Alves, Liliana, Giesbers, Else, and Daniel, Ana
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- 2021
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29. Responsible Governance for a Food and Nutrition E-Infrastructure: Case Study of the Determinants and Intake Data Platform
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Lada Timotijevic, Indira Carr, Javier De La Cueva, Tome Eftimov, Charo E. Hodgkins, Barbara Koroušić Seljak, Bent E. Mikkelsen, Trond Selnes, Pieter Van't Veer, and Karin Zimmermann
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food consumer behavior ,food consumer choice ,data quality ,interoperability ,standardization ,big data ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The focus of the current paper is on a design of responsible governance of food consumer science e-infrastructure using the case study Determinants and Intake Data Platform (DI Data Platform). One of the key challenges for implementation of the DI Data Platform is how to develop responsible governance that observes the ethical and legal frameworks of big data research and innovation, whilst simultaneously capitalizing on huge opportunities offered by open science and the use of big data in food consumer science research. We address this challenge with a specific focus on four key governance considerations: data type and technology; data ownership and intellectual property; data privacy and security; and institutional arrangements for ethical governance. The paper concludes with a set of responsible research governance principles that can inform the implementation of DI Data Platform, and in particular: consider both individual and group privacy; monitor the power and control (e.g., between the scientist and the research participant) in the process of research; question the veracity of new knowledge based on big data analytics; understand the diverse interpretations of scientists' responsibility across different jurisdictions.
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- 2022
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30. No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study
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Guri Hagberg, Hege Ihle-Hansen, Brynjar Fure, Bente Thommessen, Håkon Ihle-Hansen, Anne Rita Øksengård, Mona K. Beyer, Torgeir B. Wyller, Ebba Gløersen Müller, Sarah T. Pendlebury, and Per Selnes
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Stroke ,Cognitive impairment ,Cerebrospinal fluid ,Positron emission tomography ,Prognosis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-β peptide (Aβ42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. Methods 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ42 levels were assessed using linear regression. Results In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. Conclusions Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. Trial registration Clinicaltrials.gov ( NCT00506818 ). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.
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- 2020
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31. Årsaker til forsinkelser ved elektive operasjoner
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Heidi Værdal, Grete Helen Bratberg, and Hege Selnes Haugdahl
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prospektive studier ,operasjonssykepleie ,informasjonssystemer i operasjonsavdelingen ,forsinkelser ,elektiv kirurgi ,prospective studies ,Nursing ,RT1-120 - Abstract
Forsinkelser og strykninger under elektive operasjoner hindrer optimal drift og kan være en påkjenning for pasienter. Målet med studien var å identifisere og beskrive de faktiske årsaker til forsinkelser ved elektive operasjoner, samt omfang, varighet og andre kjennetegn ved slike forsinkelser. Studien har et flermetodisk prospektivt studiedesign. I en periode på to måneder ble alle elektronisk registrerte forsinkelser fulgt opp med strukturerte intervju. I løpet av studieperioden ble halvparten av elektive operasjoner registrert med en eller flere forsinkelser (N = 402). Informantene anga 60 ulike rotårsaker som en forklaring på forsinkelsene. I 72% av alle forsinkelser var årsaken knyttet til organisering/administrering av operasjonsplanleggingen. Forsinkelser ved elektive operasjoner skyldes i stor grad utilstrekkelig planlegging og organisering. Mer presis planlegging, informasjonsutveksling og forbedret dataverktøy kan redusere forsinkelser ved elektive operasjoner. Causes of delays in elective surgery: A prospective study Abstract Delays and cancellations in elective surgery prevent optimal services and can be stressful for patients. This study aimed to identify and describe the actual causes of delays in elective surgery, and the extent, duration and other characteristics of these delays. The study has a multi-method prospective study design. For two months, all electronically recorded delays in a Norwegian hospital were followed up with structured interviews to identify their true causes. Half of the elective surgeries recorded had one or more delays (N = 402). The delays had 60 different root causes; using qualitative content analysis, these were interpreted into 13 subcategories and four main categories, namely patient-related (17%), staff-related (10%), related to surgical ward/equipment (2%) or organizational (71%). Most delays were due to poor planning and organization of surgery. The study indicates that more precise planning, better information exchange and an improved electronic tool can reduce delays in elective surgery.
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- 2021
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32. Annotation Tools in Gastrointestinal Polyp Annotation
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Ola Selnes, Thomas Bjørsum-Meyer, Aymeric Histace, Gunnar Baatrup, and Anastasios Koulaouzidis
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annotation tool ,polyp annotation ,automated labelling ,camera capsule endoscopy ,computer-aided diagnosis ,Medicine (General) ,R5-920 - Abstract
Capsule endoscopy (CE) is a valid alternative to conventional gastrointestinal (GI) endoscopy tools. In CE, annotation tools are crucial in developing large and annotated medical image databases for training deep neural networks (DNN). We provide an overview of the described and in-use various annotation systems available, focusing on the annotation of adenomatous polyp pathology in the GI tract. Some studies present promising results regarding time efficiency by implementing automated labelling features in annotation systems. Thus, data are inadequate regarding the general overview for users, and may also be more specific on which features provided are necessary for polyp annotation.
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- 2022
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33. Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
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Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle
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- 2022
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34. Glial activation and inflammation along the Alzheimer’s disease continuum
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Kaja Nordengen, Bjørn-Eivind Kirsebom, Kristi Henjum, Per Selnes, Berglind Gísladóttir, Marianne Wettergreen, Silje Bøen Torsetnes, Gøril Rolfseng Grøntvedt, Knut K. Waterloo, Dag Aarsland, Lars N. G. Nilsson, and Tormod Fladby
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Early diagnosis ,Cerebrospinal fluid ,ELISA ,sTREM2 ,YKL-40 ,Chitinase-3-like protein 1 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer’s disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation. Methods We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker—soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction—monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers—chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker—fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn’s pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score. Results Compared to healthy controls, sTREM2 was increased in SCD (p
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- 2019
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35. Risk of lung cancer and physical activity by smoking status and body mass index, the Norwegian Women and Cancer Study
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Borch, Kristin Benjaminsen, Weiderpass, Elisabete, Braaten, Tonje, Hansen, Merethe Selnes, and Licaj, Idlir
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- 2019
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36. Community paramedicine—cost–benefit analysis and safety with paramedical emergency services in rural areas: scoping review protocol
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Hege Selnes Haugdahl, Marianne Lysne, Odd Eirik Elden, and Oddvar Uleberg
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Medicine - Abstract
Introduction Community paramedicine models have been developed around the world in response to demographic changes, healthcare system needs and reforms. The traditional role of the paramedic has primarily been to provide emergency medical response and transportation of patients to nearby medical facilities. As a response to healthcare service gaps in underserved communities and the growing professionalisation of the workforce, the role of community paramedicine has evolved as a new model of care. A community paramedicine model in one region might address other healthcare needs than a model in another region. Various terms are also in use for community paramedicine providers, with no consensus on the definition for community paramedics, although the definition used by the International Roundtable on Community Paramedicine has been widely accepted. We aimed to examine the current knowledge and possibly identify gaps in the research/knowledge base for cost–benefit analysis and safety concerning community paramedicine in rural areas using a scoping review methodology.Methods and analysis This scoping review will follow the methodology developed by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. In October 2020, we will search electronic databases (MEDLINE via PubMed, CINAHL, Cochrane and Embase) and the reference lists of key studies to identify studies for inclusion. The selection process is in two steps. First, two reviewers will independently screen identified articles for title and abstracts and, second, perform a full-text review of eligible studies for inclusion. Studies focusing on community paramedicine in rural areas, which include cost–benefit analysis or safety evaluation, will be included.Ethics and dissemination The data used are available from publicly secondary sources, therefore this study will not require ethical review. The results will be disseminated through peer-reviewed publication.
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- 2020
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37. Postpartum lifestyle interventions among women with pre-eclampsia: a scoping review protocol
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Ottar Bjerkeset, Lisbeth Uhrenfeldt, Hege Selnes Haugdahl, Heidi Linn Sandsæter, Marianne Lysne, and Julie Horn
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Medicine - Abstract
Introduction Compared to women with normotensive pregnancies, women with a history of pre-eclampsia have a roughly fourfold increased risk of developing chronic arterial hypertension and a twofold increased risk of developing cardiovascular disease (CVD). Lifestyle changes, such as increased physical activity, weight loss, smoking cessation and healthy diet, are effective for CVD prevention in the general population. However, no scoping review or systematic review of postpartum lifestyle interventions among women with pre-eclampsia have, to our best knowledge, been performed. The objective of this scoping review is to provide an overview of the available research literature on postpartum lifestyle interventions to reduce the risk of CVD among women with pre-eclampsia.Methods and analysis The protocol is based on the framework outlined by Arksey and O’Malley. Databases to be searched include: PubMed, Embase CINAHL and the JBI Database of Systematic Reviews and Implementation Reports. The search will be performed after the publication of this protocol (estimated to be 1 June 2020) and will be repeated 1 month prior to the submission for publication of the final review (estimated to be 1 January 2021). The review will consider studies that include women in the postpartum period (in particular, but not restricted to, the first 12 months after delivery), with a history of pre-eclampsia. Data will be extracted by two independent reviewers using a data extraction tool including specific details about the population, concept, context, study methods and key findings relevant to the review objective. Any disagreements between the reviewers will be resolved through discussion, or with a third reviewer. The extracted data will be presented in diagrammatic or tabular form that align with the objective of this scoping review. A narrative summary will accompany the tabulated and/or charted results and will describe how the results relate to the reviews objective and questions.Ethics and dissemination Since all data will be obtained from publicly available materials, the proposed scoping review does not require ethical approval. The results will be submitted for publication in an open-access peer-reviewed journal and presented at relevant conferences.
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- 2020
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38. Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
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Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle
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- 2021
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39. Similar pattern of atrophy in early‐ and late‐onset Alzheimer's disease
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Carl Eckerström, Niklas Klasson, Erik Olsson, Per Selnes, Sindre Rolstad, and Anders Wallin
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Early‐onset AD ,Late‐onset AD ,MRI ,Neuroimaging ,Hippocampus ,Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Introduction Previous research on structural changes in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) have reported inconsistent findings. Methods In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years. Results Hippocampal atrophy is the most prominent feature of both EOAD and LOAD compared with controls. Direct comparison between EOAD and LOAD showed that the differences between the groups did not remain after correcting for age. Discussion Structurally, EOAD and LOAD does not seem to be different nosological entities. The difference in brain volumes between the groups compared with controls is likely due to age‐related atrophy.
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- 2018
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40. Chlorine Can Bring Chemistry to Life: Introduce Students to Chemistry without Tackling the Whole Periodic Table At Once.
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Chlorine Chemistry Council, Washington, DC. and Selnes, Marvin
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Recognizing basic elements as building blocks is essential to the study of science, and looking closer at one element in particular, chlorine, can help ignite students' interest in chemistry. This document contains a 2-day study of building block chemistry using basic concepts and easy-to-find materials. Teaching materials include objectives, safety notes, disposal of solutions, teaching strategies, sample student data table, chlorine background information, chlorine chemistry and product tree, and student worksheets. (MKR)
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- 1992
41. No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study
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Hagberg, Guri, Ihle-Hansen, Hege, Fure, Brynjar, Thommessen, Bente, Ihle-Hansen, Håkon, Øksengård, Anne Rita, Beyer, Mona K., Wyller, Torgeir B., Müller, Ebba Gløersen, Pendlebury, Sarah T., and Selnes, Per
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- 2020
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42. CSF synapse marker changes in predementia Alzheimer´s Disease: AMPA receptor modulators NPTX2 and NPTXR mediate cognition within A/T/N stages.
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Kirsebom, Bjørn‐Eivind, Nilsson, Johanna, Vromen, Eleonora M., Jarholm, Jonas Alexander, Tecelao, Sandra, Selnes, Per, Aarsland, Dag, Grøntvedt, Gøril Rolfseng, Rongve, Arvid, Skogseth, Ragnhild E, Visser, Pieter Jelle, Brinkmalm, Ann, Blennow, Kaj, and Fladby, Tormod
- Abstract
Background: Synapse pathology has been linked to excitotoxicity and glutamate receptor dysregulation (such as AMPAR) in Alzheimer´s Disease (AD) progression. Of the core cerebrospinal fluid (CSF) AD biomarkers for amyloid, tau pathology and neurodegeneration (A/T/N), T/N status is proposed to reflect levels of neuronal plasticity, but fluid biomarkers for precision interventions in subgroups with increased excitotoxicity are lacking. Herein, we assess group differences of 19 CSF synapse markers including the AMPAR‐modulating NPTX, in both cognitively normal (CN) and Mild Cognitive Impairment (MCI) with either A+/T‐/N‐ and A+/T or N+ (A+/T/N+) as compared to CN A‐/T‐/N‐ and assess relationships with verbal memory recall and hippocampal volume. Methods: A/T/N was determined using the CSF Aβ42/40 ratio, p‐tau181 and total‐tau in predementia AD cases (n = 194) and CN participants with normal AD biomarkers (n = 145) in the Dementia Disease Initiation cohort. CSF synapse marker concentrations were determined using mass‐spectrometry (table 1) and ELISA for GAP‐43. Adjusted for age and sex, we compared marker concentrations between CN cases (A+/T‐/N‐ n = 20; A+/T/N+ n = 40) and MCI cases (A+/T‐/N‐ n = 25;A+/T/N+ n = 109) with CN A‐/T‐/N‐ (n = 145) as the reference group. Associations to verbal memory recall and brain imaging were performed in the total sample and respective A/T/N groups adjusted for covariates. Results p<.01 were considered significant. Results: Top markers based on between‐group results are reported (Table 1 & figure 1‐2 for all markers). Compared to CN A‐/T‐/N‐, 14‐3‐3 ζ/δ concentrations were higher in all A+/T/N+ groups (p<.001), but unaltered in A+/T‐/N‐ groups. In A+/T‐/N‐, NPTX2 concentrations were lower in MCI (p<.001) but not in CN. In A+/T/N+, NPTX2 was higher in CN (p<.001) but not in MCI. 14‐3‐3 ζ/δ was associated with worse memory in the total sample (p<.001) but not in the A+ groups. Lower NPTX2 was associated with worse memory in the total sample (p<.001) and in both A+ groups (p<.01; p<001). Neither 14‐3‐3 ζ/δ nor NPTX2 were significantly associated with hippocampal volume (figure 2). Conclusion: Overall, increased 14‐3‐3 ζ/δ was most closely associated with worse memory recall. Lower NPTX2 was linked to poorer cognitive status within A+ groups, suggesting links to AMPAR dysregulation and excitotoxicity. [ABSTRACT FROM AUTHOR]
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- 2023
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43. Innovation and Collaboration: Opportunities for the European Seaweed Sector in Global Value Chains
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Trond Selnes, Else Giesbers, and Sander W. K. van den Burg
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seaweed ,value chain ,collaboration ,innovation ,governance ,Naval architecture. Shipbuilding. Marine engineering ,VM1-989 ,Oceanography ,GC1-1581 - Abstract
The European seaweed sector transitions from harvesting wild stocks only to harvesting and farming seaweed. This transition comes with the need to rethink the role of the European sector on the global scale; insight is needed into the organization of, and innovation in, the global seaweed value chain. This article presents results from our study on value chains using Gereffi’s conceptual framework. A systematic review of scientific publications published between 2010 and 2020 was executed for five markets: pharmaceuticals, bioplastics, biostimulants, alginate and cosmetics. It is concluded that innovation in the use of seaweed takes place across the globe and thus that a focus on high-value applications alone will not set the nascent European seaweed sector apart from established producing regions such as Asia. The studied global value chains are organised around strong lead firms that require suppliers to produce according to codified product characteristics. The European seaweed sector needs to increase the collaboration and develop joint efforts to develop safe and sustainable products that meet the demands of regulators, lead firms and consumers. Stronger coordination in the value chain will facilitate further business development, by stimulating collaboration and innovations.
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- 2021
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44. Association between total-Tau and brain atrophy one year after first-ever stroke
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Hege Ihle-Hansen, Guri Hagberg, Brynjar Fure, Bente Thommessen, Morten W. Fagerland, Anne R. Øksengård, Knut Engedal, and Per Selnes
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Stroke ,Neurodegeneration ,Cerebral spinal fluid ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke. Methods We included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression. Results One hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta −0.50, 95% CI −565.9, −78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes. Conclusion T-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons. Trial registration Clinicaltrials.gov NCT00506818 , July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.
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- 2017
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45. DEveloping Blood-Brain barrier arterial spin labeling as a non-Invasive Early biomarker (DEBBIE)
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Padrela, B., Tee, M., Sneve, M., Mahroo, A., Geier, O., Thomas, D., Morgan, C., Moyaert, P., Ozturk, E., Nordhøy, W., Pålhaugen, L., Linn, J., Selnes, P., Eickel, K., Konstandin, S., Kuijer, J., Hoinkiss, D., Breutigam, N., Buck, M., Achten, R., Barkhof, F., Hilal, S., Fladby, T., Anazodo, U., (0000-0002-3201-6002) Petr, J., Mutsaerts, H. J. M. M., Günther, M., Padrela, B., Tee, M., Sneve, M., Mahroo, A., Geier, O., Thomas, D., Morgan, C., Moyaert, P., Ozturk, E., Nordhøy, W., Pålhaugen, L., Linn, J., Selnes, P., Eickel, K., Konstandin, S., Kuijer, J., Hoinkiss, D., Breutigam, N., Buck, M., Achten, R., Barkhof, F., Hilal, S., Fladby, T., Anazodo, U., (0000-0002-3201-6002) Petr, J., Mutsaerts, H. J. M. M., and Günther, M.
- Abstract
One of the earliest signs of Alzheimer’s disease (AD) is the loss of blood-brain barrier (BBB) integrity. Arterial spin labeling (ASL) MRI is a non-invasive way to measure perfusion and several other hemodynamic and physiological parameters, including vascular permeability. The DEveloping BBB-ASL as non-Invasive Early biomarker (DEBBIE) consortium aims to develop and integrate innovative techniques to allow robust BBB permeability assessments by ASL to develop a sensitive, non-invasive, and early biomarker for AD and related dementias. This work summarizes our planned efforts to develop and establish an MRI-based BBB permeability biomarker.
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- 2023
46. DEveloping BBB-ASL as non-Invasive Early biomarker of Alzheimer’s Disease (DEBBIE-AD): Study design
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Padrela, B. E., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., Zhu, Y. D., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B., Giessen, E., Muller, M., Fjell, A. M., Walhovd, K. B., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., Mutsaerts, H. J. M. M., Padrela, B. E., Mahroo, A., Tee, M., Sneve, M. H., Moyaert, P., Geier, O., Kuijer, J. P. A., Beun, S., Nordhøy, W., Zhu, Y. D., Buck, M. A., Hoinkiss, D. C., Konstandin, S., Huber, J., Wiersinga, J., Rikken, R., Leeuw, D., Grydeland, H., Tippett, L., Cawston, E. E., Ozturk-Isik, E., Linn, J., Brandt, M., Tijms, B., Giessen, E., Muller, M., Fjell, A. M., Walhovd, K. B., Pålhaugen, L., Selnes, P., Clement, P., Achten, E., Anazodo, U., Barkhof, F., Hilal, S., Fladby, T., Eickel, K., Morgan, C., Thomas, D. L., (0000-0002-3201-6002) Petr, J., Günther, M., and Mutsaerts, H. J. M. M.
- Abstract
Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesized to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Arterial spin labeling (ASL) perfusion MRI has recently been adapted to map the BBB permeability non-invasively. This article outlines the study design of the DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium, focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods: DEBBIE-AD consists of 13 cohorts enrolling participants from subjective cognitive decline to AD, as well as healthy controls across the lifespan. The reproducibility and accuracy of BBB-ASL will be evaluated in healthy participants, and its clinical value will be evaluated with both established and novel AD biomarkers. Expected endpoints: DEBBIE-AD aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies, which may provide new targets for treatment.
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- 2023
47. Diffusion tensor and restriction spectrum imaging reflect different aspects of neurodegeneration in Parkinson's disease.
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Tuva R Hope, Per Selnes, Irena Rektorová, Lubomira Anderkova, Nela Nemcova-Elfmarkova, Zuzana Balážová, Anders Dale, Atle Bjørnerud, and Tormod Fladby
- Subjects
Medicine ,Science - Abstract
To meet the need for Parkinson's disease biomarkers and evidence for amount and distribution of pathological changes, MRI diffusion tensor imaging (DTI) has been explored in a number of previous studies. However, conflicting results warrant further investigations. As tissue microstructure, particularly of the grey matter, is heterogeneous, a more precise diffusion model may benefit tissue characterization. The purpose of this study was to analyze the diffusion-based imaging technique restriction spectrum imaging (RSI) and DTI, and their ability to detect microstructural changes within brain regions associated with motor function in Parkinson's disease. Diffusion weighted (DW) MR images of a total of 100 individuals, (46 Parkinson's disease patients and 54 healthy controls) were collected using b-values of 0-4000s/mm2. Output diffusion-based maps were estimated based on the RSI-model combining the full set of DW-images (Cellular Index (CI), Neurite Density (ND)) and DTI-model combining b = 0 and b = 1000 s/mm2 (fractional anisotropy (FA), Axial-, Mean- and Radial diffusivity (AD, MD, RD)). All parametric maps were analyzed in a voxel-wise group analysis, with focus on typical brain regions associated with Parkinson's disease pathology. CI, ND and DTI diffusivity metrics (AD, MD, RD) demonstrated the ability to differentiate between groups, with strongest performance within the thalamus, prone to pathology in Parkinson's disease. Our results indicate that RSI may improve the predictive power of diffusion-based MRI, and provide additional information when combined with the standard diffusivity measurements. In the absence of major atrophy, diffusion techniques may reveal microstructural pathology. Our results suggest that protocols for MRI diffusion imaging may be adapted to more sensitive detection of pathology at different sites of the central nervous system.
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- 2019
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48. A Novel Iron Chloride Red-Ox Concentration Flow Cell Battery (ICFB) Concept; Power and Electrode Optimization
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Robert Bock, Björn Kleinsteinberg, Bjørn Selnes-Volseth, and Odne Stokke Burheim
- Subjects
energy storage ,redox flow cell ,concentration flow cell ,iron chloride ,Technology - Abstract
For renewable energies to succeed in replacing fossil fuels, large-scale and affordable solutions are needed for short and long-term energy storage. A potentially inexpensive approach of storing large amounts of energy is through the use of a concentration flow cell that is based on cheap and abundant materials. Here, we propose to use aqueous iron chloride as a reacting solvent on carbon electrodes. We suggest to use it in a red-ox concentration flow cell with two compartments separated by a hydrocarbon-based membrane. In both compartments the red-ox couple of iron II and III reacts, oxidation at the anode and reduction at the cathode. When charging, a concentration difference between the two species grows. When discharging, this concentration difference between iron II and iron III is used to drive the reaction. In this respect it is a concentration driven flow cell redox battery using iron chloride in both solutions. Here, we investigate material combinations, power, and concentration relations.
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- 2021
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49. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. 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Hyman, Linda, S Hynan, Laura, Ibanez, Gail, P Jarvik, Suman, Jayadev, Lee-Way, Jin, Kim, Johnson, Leigh, Johnson, M Ilyas Kamboh, Anna, M Karydas, Mindy, J Katz, Jeffrey, A Kaye, C Dirk Keene, Aisha, Khaleeq, Ronald, Kim, Janice, Knebl, Neil, W Kowall, Joel, H Kramer, Pavel, P Kuksa, Frank, M LaFerla, James, J Lah, Eric, B Larson, Chien-Yueh, Lee, Edward, B Lee, Alan, Lerner, Yuk Yee Leung, James, B Leverenz, Allan, I Levey, Mingyao, Li, Andrew, P Lieberman, Richard, B Lipton, Mark, Logue, Constantine, G Lyketsos, John, Malamon, Douglas, Mains, Daniel, C Marson, Frank, Martiniuk, Deborah, C Mash, Eliezer, Masliah, Paul, Massman, Arjun, Masurkar, Wayne, C McCormick, Susan, M McCurry, Andrew, N McDavid, Ann, C McKee, Marsel, Mesulam, Jesse, Mez, Bruce, L Miller, Carol, A Miller, Joshua, W Miller, Thomas, J Montine, Edwin, S Monuki, John, C Morris, Amanda, J Myers, Trung, Nguyen, Sid, O'Bryant, John, M Olichney, Marcia, Ory, Raymond, Palmer, Joseph, E Parisi, Henry, L Paulson, Valory, 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Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
- Published
- 2022
50. Glial activation and inflammation along the Alzheimer’s disease continuum
- Author
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Nordengen, Kaja, Kirsebom, Bjørn-Eivind, Henjum, Kristi, Selnes, Per, Gísladóttir, Berglind, Wettergreen, Marianne, Torsetnes, Silje Bøen, Grøntvedt, Gøril Rolfseng, Waterloo, Knut K., Aarsland, Dag, Nilsson, Lars N. G., and Fladby, Tormod
- Published
- 2019
- Full Text
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