SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Vos Pieter) "

Sökning: WFRF:(Vos Pieter)

  • Resultat 1-40 av 40
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  •  
2.
  • El Farissi, Mohamed, et al. (författare)
  • Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI
  • 2021
  • Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 14:18, s. 2047-2055
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI).BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited.METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed.RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50).CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.
  •  
3.
  • Bos, Isabelle, et al. (författare)
  • Cerebrovascular and amyloid pathology in predementia stages : the relationship with neurodegeneration and cognitive decline
  • 2017
  • Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics.RESULTS: MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline.CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.
  •  
4.
  • Bos, Isabelle, et al. (författare)
  • Correction to : Cerebrovascular and amyloid pathology in predementia stages
  • 2018
  • Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 10:56
  • Tidskriftsartikel (refereegranskat)abstract
    • Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables 1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables.
  •  
5.
  • Bos, Isabelle, et al. (författare)
  • The frequency and influence of dementia risk factors in prodromal Alzheimer's disease
  • 2017
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 56, s. 33-40
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
  •  
6.
  • Delvenne, Aurore, et al. (författare)
  • CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease
  • 2024
  • Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279.
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: We aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics.METHODS: Individuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N- based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance.RESULTS: Only a few individuals were A+T+Ng-. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng- and A+T+NfL-, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV-, A+T+HCV+ showed few proteomic changes, associated with oxidative stress.DISCUSSION: Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology.HIGHLIGHTS: In Alzheimer's disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.
  •  
7.
  • El Farissi, Mohamed, et al. (författare)
  • A randomised trial of selective intracoronary hypothermia during primary PCI
  • 2024
  • Ingår i: EuroIntervention. - : European Society of Cardiology. - 1774-024X .- 1969-6213. ; 20:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking.AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI.METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months.RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53).CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).
  •  
8.
  • Franke, Andre, et al. (författare)
  • Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
  • Tidskriftsartikel (refereegranskat)abstract
    • We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
  •  
9.
  • Gustavsson, Anders, et al. (författare)
  • Corrigendum to “Cost of disorders of the brain in Europe 2010” [Eur. Neuropsychopharmacol. 21 (2011) 718–779]
  • 2012
  • Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:3, s. 237-238
  • Tidskriftsartikel (refereegranskat)abstract
    • The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.
  •  
10.
  • Gustavsson, Anders, et al. (författare)
  • Cost of disorders of the brain in Europe 2010.
  • 2011
  • Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
  •  
11.
  • Handels, Ron L. H., et al. (författare)
  • Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers
  • 2017
  • Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:8, s. 903-912
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.RESULTS: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.DISCUSSION: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.
  •  
12.
  • Homann, Jan, et al. (författare)
  • Genome-Wide Association Study of Alzheimer's Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Dataset.
  • 2022
  • Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.
  •  
13.
  • Hong, Shengjun, et al. (författare)
  • Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset.
  • 2020
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.
  •  
14.
  • Huijben, Jilske A., et al. (författare)
  • Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
  • 2019
  • Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.
  •  
15.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
  •  
16.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
  •  
17.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
  •  
18.
  • Kim, Min, et al. (författare)
  • Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort
  • 2019
  • Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 15:6, s. 817-827
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.
  •  
19.
  • Küçükali, Fahri, et al. (författare)
  • Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits
  • 2023
  • Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 19:6, s. 2317-2331
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes.METHODS: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).RESULTS: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.DISCUSSION: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.
  •  
20.
  • Lewczuk, Piotr, et al. (författare)
  • Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
  • 2018
  • Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
  • Tidskriftsartikel (refereegranskat)abstract
    • In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
  •  
21.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
  • 2018
  • Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
  •  
22.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
  •  
23.
  • Neumann, Alexander, et al. (författare)
  • Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.
  • 2023
  • Ingår i: Genome medicine. - 1756-994X. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n=205 controls, n=546 mild cognitive impairment, n=222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analysesof the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.
  •  
24.
  • Prins, Jonne T H, et al. (författare)
  • Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: An international, retrospective matched case-control study.
  • 2022
  • Ingår i: The journal of trauma and acute care surgery. - 2163-0763. ; 93:6, s. 727-735
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR.An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS.Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar.Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables.Therapeutic/Care Management; Level III.
  •  
25.
  • Rados, Matea, et al. (författare)
  • Diagnostic value of MRI in the presurgical evaluation of patients with epilepsy: influence of field strength and sequence selection: a systematic review and meta-analysis from the E-PILEPSY Consortium.
  • 2022
  • Ingår i: Epileptic disorders. - : Wiley. - 1950-6945 .- 1294-9361. ; 24:2, s. 323-342
  • Tidskriftsartikel (refereegranskat)abstract
    • MRI is a cornerstone in presurgical evaluation of epilepsy. Despite guidelines, clinical practice varies. In light of the E-PILEPSY pilot reference network, we conducted a systematic review and meta-analysis on the diagnostic value of MRI in the presurgical evaluation of epilepsy patients. We included original research articles on diagnostic value of higher MRI field strength and guideline-recommended and additional MRI sequences in detecting an epileptogenic lesion in adult or paediatric epilepsy surgery candidates. Lesion detection rate was used as a metric in meta-analysis. Eighteen studies were included for MRI field strength and 25 for MRI sequences, none were free from bias. In patients with normal MRI at lower-field strength, 3T improved lesion detection rate by 18% and 7T by 23%. Field strengths higher than 1.5T did not have higher lesion detection rates in patients with hippocampal sclerosis (HS). The lesion detection rate of epilepsy-specific MRI protocols was 83% for temporal lobe epilepsy (TLE) patients. Dedicated MRI protocols and evaluation by an experienced epilepsy neuroradiologist increased lesion detection. For HS, 3DT1, T2, and FLAIR each had a lesion detection rate at around 90%. Apparent diffusion coefficient indices had a lateralizing value of 33% for TLE. DTI fractional anisotropy and mean diffusivity had a localizing value of 8% and 34%. A dedicated MRI protocol and expert evaluation benefits lesion detection rate in epilepsy surgery candidates. If patients remain MRI negative, imaging at higher-field strength may reveal lesions. In HS, apparent diffusion coefficient indices may aid lateralization and localization more than increasing field strength. DTI can add further diagnostic information. For other additional sequences, the quality and number of studies is insufficient to draw solid conclusions. Our findings may be used as evidence base for developing new high-quality MRI studies and clinical guidelines.
  •  
26.
  • Reijs, Babette L R, et al. (författare)
  • Association Between Later Life Lifestyle Factors and Alzheimer's Disease Biomarkers in Non-Demented Individuals : A Longitudinal Descriptive Cohort Study
  • 2017
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 60:4, s. 1387-1395
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lifestyle factors have been associated with the risk of dementia, but the association with Alzheimer's disease (AD) remains unclear.OBJECTIVE: To examine the association between later life lifestyle factors and AD biomarkers (i.e., amyloid-β 1-42 (Aβ42) and tau in cerebrospinal fluid (CSF), and hippocampal volume) in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In addition, to examine the effect of later life lifestyle factors on developing AD-type dementia in individuals with MCI.METHODS: We selected individuals with SCD (n = 111) and MCI (n = 353) from the DESCRIPA and Kuopio Longitudinal MCI studies. CSF Aβ42 and tau concentrations were assessed with ELISA assay and hippocampal volume with multi-atlas segmentation. Lifestyle was assessed by clinical interview at baseline for: social activity, physical activity, cognitive activity, smoking, alcohol consumption, and sleep. We performed logistic and Cox regression analyses adjusted for study site, age, gender, education, and diagnosis. Prediction for AD-type dementia was performed in individuals with MCI only.RESULTS: Later life lifestyle factors were not associated with AD biomarkers or with conversion to AD-type dementia. AD biomarkers were strongly associated with conversion to AD-type dementia, but these relations were not modulated by lifestyle factors. Apolipoprotein E (APOE) genotype did not influence the results.CONCLUSIONS: Later life lifestyle factors had no impact on key AD biomarkers in individuals with SCD and MCI or on conversion to AD-type dementia in MCI.
  •  
27.
  • Shi, Liu, et al. (författare)
  • Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
  • 2020
  • Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
  •  
28.
  • Shi, Liu, et al. (författare)
  • Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.
  • 2019
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 15:11, s. 1478-1488
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.4001 plasma proteins were measured in two groups of participants (discovery group=516, replication group=365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.A panel of proteins (n=44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve=0.78) and the replication group (area under the curve=0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.
  •  
29.
  • Shi, Liu, et al. (författare)
  • Replication study of plasma proteins relating to Alzheimer's pathology.
  • 2021
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 17:9, s. 1452-1464
  • Tidskriftsartikel (refereegranskat)abstract
    • This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
  •  
30.
  • Stamate, Daniel, et al. (författare)
  • A metabolite-based machine learning approach to diagnose Alzheimer-type dementia in blood : Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort
  • 2019
  • Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 5:C, s. 933-938
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionMachine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer Disease (AD). Here we set out to test the performance of metabolites in blood to categorize AD when compared to CSF biomarkers.MethodsThis study analyzed samples from 242 cognitively normal (CN) people and 115 with AD‐type dementia utilizing plasma metabolites (n = 883). Deep Learning (DL), Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were used to differentiate AD from CN. These models were internally validated using Nested Cross Validation (NCV).ResultsOn the test data, DL produced the AUC of 0.85 (0.80–0.89), XGBoost produced 0.88 (0.86–0.89) and RF produced 0.85 (0.83–0.87). By comparison, CSF measures of amyloid, p‐tau and t‐tau (together with age and gender) produced with XGBoost the AUC values of 0.78, 0.83 and 0.87, respectively.DiscussionThis study showed that plasma metabolites have the potential to match the AUC of well‐established AD CSF biomarkers in a relatively small cohort. Further studies in independent cohorts are needed to validate whether this specific panel of blood metabolites can separate AD from controls, and how specific it is for AD as compared with other neurodegenerative disorders.
  •  
31.
  • Van Daele, Ruth, et al. (författare)
  • Concomitant use of isavuconazole and CYP3A4/5 inducers : Where pharmacogenetics meets pharmacokinetics
  • 2021
  • Ingår i: Mycoses. - : John Wiley & Sons. - 0933-7407 .- 1439-0507. ; 64:9, s. 1111-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin. Objectives We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype. Patients We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations. Results These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction. Conclusions CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.
  •  
32.
  • van Maurik, Ingrid S., et al. (författare)
  • Biomarker-based prognosis for people with mild cognitive impairment (ABIDE) : a modelling study
  • 2019
  • Ingår i: Lancet Neurology. - : The Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 18:11, s. 1034-1044
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia.METHODS: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models-a demographics model, a hippocampal volume model, and a CSF biomarkers model-by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework.FINDINGS: We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59-0·65), validated hippocampal volume model (0·67, 0·62-0·72), and updated CSF biomarkers model (0·72, 0·68-0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71-0·76).INTERPRETATION: We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour.
  •  
33.
  • van Rossum, Ineke A, et al. (författare)
  • Injury markers predict time to dementia in subjects with MCI and amyloid pathology.
  • 2012
  • Ingår i: Neurology. - 1526-632X. ; 79:17, s. 1809-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.
  •  
34.
  • Visser, Pieter Jelle, et al. (författare)
  • Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer's disease.
  • 2020
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Alzheimer's disease (AD) is characterised by abnormal amyloid beta and tau processing. Previous studies reported that cerebrospinal fluid (CSF) total tau (t-tau) levels vary between patients. Here we show that CSF t-tau variability is associated with distinct impairments in neuronal plasticity mediated by gene repression factors SUZ12 and REST. AD individuals with abnormal t-tau levels have increased CSF concentrations of plasticity proteins regulated by SUZ12 and REST. AD individuals with normal t-tau, on the contrary, have decreased concentrations of these plasticity proteins and increased concentrations in proteins associated with blood-brain and blood CSF-barrier dysfunction. Genomic analyses suggested that t-tau levels in part depend on genes involved in gene expression. The distinct plasticity abnormalities in AD as signaled by t-tau urge the need for personalised treatment.
  •  
35.
  • Vos, Stephanie J B, et al. (författare)
  • Modifiable Risk Factors for Prevention ofDementia in Midlife, Late Life and the Oldest-Old: Validation of the LIBRA Index.
  • 2017
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 58:2, s. 537-547
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individual's prevention potential for dementia.We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old.9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individual's LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2y, range 1-16).In midlife (55-69y, n=3,256) and late life (70-79y, n=4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97y, n=1,811), higher LIBRA scores did not increase the risk for dementia.LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.
  •  
36.
  • Vos, Stephanie J. B., et al. (författare)
  • Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage
  • 2015
  • Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 138:5, s. 1327-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
  •  
37.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
  •  
38.
  • Wesenhagen, Kirsten E. J., et al. (författare)
  • Effects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition
  • 2022
  • Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : John Wiley & Sons. - 2352-8729. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E Ɛ4 genotype.Methods: We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery, and Metabolic Syndrome in Men. In total, 1149 proteins were measured with liquid chromatography mass spectrometry with multiple reaction monitoring/Rules-Based Medicine, tandem mass tag mass spectrometry, and SOMAscan. We tested associations between age and protein levels in linear models and tested enrichment for Reactome pathways.Results: Levels of 252 proteins increased with age independently of amyloid status. These proteins were associated with immune and signaling processes. Levels of 21 proteins decreased with older age exclusively in amyloid abnormal participants and these were enriched for extracellular matrix organization.Discussion: We found amyloid-independent and -dependent CSF proteome changes with older age, perhaps representing physiological aging and early AD pathology.
  •  
39.
  • Westwood, Sarah, et al. (författare)
  • Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort
  • 2020
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 74:1, s. 213-225
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.
  •  
40.
  • Xu, Jin, et al. (författare)
  • Sex-Specific Metabolic Pathways Were Associated with Alzheimer's Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort
  • 2021
  • Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives.METHODS: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites' discriminatory performance in AD.RESULTS: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046).CONCLUSIONS: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-40 av 40
Typ av publikation
tidskriftsartikel (40)
Typ av innehåll
refereegranskat (39)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
Visser, Pieter Jelle (28)
Vos, Stephanie J. B. (27)
Scheltens, Philip (26)
Tsolaki, Magda (24)
Engelborghs, Sebasti ... (21)
Vandenberghe, Rik (20)
visa fler...
Teunissen, Charlotte ... (20)
Freund-Levi, Yvonne, ... (20)
Popp, Julius (19)
Lleó, Alberto (18)
Frisoni, Giovanni B. (18)
Zetterberg, Henrik, ... (16)
Lovestone, Simon (16)
Bos, Isabelle (16)
Blennow, Kaj, 1958 (15)
Martínez-Lage, Pablo (15)
Soininen, Hilkka (14)
Bertram, Lars (14)
Johannsen, Peter (14)
Streffer, Johannes (14)
Alcolea, Daniel (13)
Hampel, Harald (13)
Dobricic, Valerija (13)
Barkhof, Frederik (12)
Rami, Lorena (12)
Sleegers, Kristel (12)
Verhey, Frans (12)
Wallin, Anders, 1950 (11)
Frölich, Lutz (11)
Tainta, Mikel (11)
Peyratout, Gwendolin ... (11)
Bordet, Régis (11)
Tijms, Betty M. (10)
Legido-Quigley, Cris ... (10)
Gabel, Silvy (10)
van der Flier, Wiesj ... (9)
Molinuevo, José Luis (9)
Kornhuber, Johannes (9)
Wiltfang, Jens (9)
Herukka, Sanna-Kaisa (9)
Verhey, Frans R. J. (9)
Blin, Olivier (9)
Kettunen, Petronella (8)
Verbeek, Marcel M (8)
Peters, Oliver (8)
Maier, Wolfgang (8)
Santana, Isabel (8)
Richardson, Jill C (8)
Jansen, Willemijn J. (8)
Meersmans, Karen (8)
visa färre...
Lärosäte
Örebro universitet (27)
Karolinska Institutet (27)
Göteborgs universitet (25)
Lunds universitet (13)
Umeå universitet (2)
Uppsala universitet (2)
visa fler...
Karlstads universitet (2)
Stockholms universitet (1)
Linköpings universitet (1)
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (40)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (40)
Samhällsvetenskap (2)
Naturvetenskap (1)
Teknik (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy