| 1. |
- 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.
|
|
| 2. |
|
|
| 3. |
- Bailey, D. L., et al.
(författare)
-
Combined PET/MRI : from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tubingen, Germany
- 2016
-
Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 18:5, s. 637-650
-
Tidskriftsartikel (refereegranskat)abstract
- This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tubingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.
|
|
| 4. |
|
|
| 5. |
- Barthel, Roland, 1967, et al.
(författare)
-
Global change impacts on groundwater in Southern Germany-Part 2: Socioeconomic aspects
- 2011
-
Ingår i: Grundwasser. - : Springer Science and Business Media LLC. - 1430-483X .- 1432-1165. ; 16:4, s. 259-268
-
Tidskriftsartikel (refereegranskat)abstract
- In order to account for complex interactions between humans climate and the water cycle, the research consortium GLOWA-Danube http://www. glowa-danube. de has developed the simulation system DANUBIA which consists of 17 coupled models. DANUBIA was applied to investigate various impacts of global-change between 2011 and 2060 in the Upper Danube Catchment. This article describes part 2 of an article series with investigations of socio-economic aspects, while part 1 (Barthel et al. in Grundwasser 16(4), doi:10. 1007/s007-011-01794, 2011) deals with natural-spatial aspects. The principles of socio-economic actor-modeling and interactions between socio-economic and natural science model components are described here. We present selected simulations that show impacts on groundwater from changes in agriculture, tourism, economy, domestic water users and water supply. Despite decreases in water consumption, the scenario simulations show significant decreases in groundwater quantity. On the other hand, groundwater quality will likely be influenced more severely by land use changes compared to direct climatic causes. However, overall changes will not be dramatic. © 2011 Springer-Verlag.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- van Rheenen, W, et al.
(författare)
-
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
-
Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
|
|
| 9. |
- Barthel, Roland, 1967, et al.
(författare)
-
Aspects of choosing appropriate concepts for modelling groundwater resources in regional integrated water resources management - Examples from the Neckar (Germany) and Ouémé catchment (Benin)
- 2008
-
Ingår i: Physics and Chemistry of the Earth. - : Elsevier BV. - 1474-7065. ; 33:1-2, s. 92-114
-
Tidskriftsartikel (refereegranskat)abstract
- Two regional groundwater flow models (Neckar catchment, Germany, 14,000 km2, and Southern Ouémé Basin, Benin, 11,000 km2) were developed within the framework of the integrated management project 'RIVERTWIN' (www.rivertwin.org). Both models were evaluated with respect to the question if the chosen modelling approaches (multi-layered finite difference numerical flow modelling, steady state and transient) are appropriate in view of the existing management problems in the catchments, the data availability and the hydrogeological and hydrological conditions in the basins. It is shown that neither the model in the well-investigated, data-rich basin in Western Europe with its highly developed water related infrastructure, nor the model in the hydrogeologically less well-known and less developed basin in Western Africa provide results that are fully applicable to the main regional management tasks. In the case of the Ouémé, the groundwater related problems are foremost of local character and therefore cannot be addressed by regional models in a meaningful way. Data scarcity and complex, unfavourable geological conditions (crystalline rocks, discontinuous aquifers) support the conclusion that numerical 3D groundwater flow models are currently not helpful to manage groundwater related management problems in the Ouémé basin. A better understanding of regional hydrological surface and subsurface processes is required first. Methods for a reliable estimation of groundwater recharge and subsequently groundwater availability were identified as the most urgently needed tool for meaningful groundwater management in view of climatic, demographic and land use change. In the Neckar catchment the results of the analysis are less pronounced; here regional groundwater problems could clearly benefit from a physically based 3D model since the hydrogeological system is strictly stratified with several important aquifers in the vertical sequence. As a general conclusion it can be stated that regional scale groundwater flow modelling concepts seem to be difficult to integrate in management systems and difficult to transfer from one basin to another. This means the question of how to represent the groundwater resources appropriately has to be discussed very thoroughly for any new integrated water resources management problem. It is not possible to give a final recommendation on which modelling concept is the most appropriate one in regional integrated modelling and management. Hence, this article is only intended to provide an in depth discussion of the aspects that need to be considered in the process of choosing appropriate modelling concepts. © 2007 Elsevier Ltd. All rights reserved.
|
|
| 10. |
- Barthel, Roland, 1967, et al.
(författare)
-
Global change impacts on groundwater in Southern Germany-Part 1: Natural aspects
- 2011
-
Ingår i: Grundwasser. - : Springer Science and Business Media LLC. - 1430-483X .- 1432-1165. ; 16:4, s. 247-257
-
Tidskriftsartikel (refereegranskat)abstract
- In order to account for complex interactions between humans climate and the water cycle, the research consortium GLOWA-Danube (www. glowa-danube. de) has developed the simulation system DANUBIA which consists of 17 coupled models. DANUBIA was applied to investigate various impacts of global-change between 2011 and 2060 in the Upper Danube Catchment. This article represents part 1 of an article series and describes groundwater and natural aspects of the investigations, while part 2 describes socio-economic aspects (Barthel et al. in Grundwaser 16(4), doi:10. 1007/s00767-011-0180-y, 2011). Here we describe concepts of GLOWA-Danube and DANUBIA as well as groundwater-related model components. This leads to selected simulation results for water balance, groundwater quantity and quality. The chosen scenarios show decreasing precipitation, increasing temperatures, and changes in the annual distribution that lead to significant decreases in groundwater recharge. Regional predictions of groundwater quality were difficult to achieve because of complex soil and groundwater processes. However, climatic change will probably have little impact. © 2011 Springer-Verlag.
|
|
