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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.

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.

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.

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

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.

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.

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

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

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.

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.

The gastrointestinal (GI) tract, particularly the small bowel (SB), can be challenging for novel investigation tools [...]

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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]

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.

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.

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.

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.