| 1. |
- Mattsson, Niklas, et al.
(författare)
-
Comparing 18F-AV-1451 with CSF t-tau and p-tau for diagnosis of Alzheimer disease
- 2018
-
Ingår i: Neurology. - 0028-3878. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- To compare PET imaging of tau pathology with CSF measurements (total tau [t-tau] and phosphorylated tau [p-tau]) in terms of diagnostic performance for Alzheimer disease (AD).We compared t-tau and p-tau and 18F-AV-1451 in 30 controls, 14 patients with prodromal AD, and 39 patients with Alzheimer dementia, recruited from the Swedish BioFINDER study. All patients with AD (prodromal and dementia) were screened for amyloid positivity using CSF β-amyloid 42. Retention of 18F-AV-1451 was measured in a priori specified regions, selected for known associations with tau pathology in AD.Retention of 18F-AV-1451 was markedly elevated in Alzheimer dementia and moderately elevated in prodromal AD. CSF t-tau and p-tau was increased to similar levels in both AD dementia and prodromal AD. 18F-AV-1451 had very good diagnostic performance for Alzheimer dementia (area under the receiver operating characteristic curve [AUROC] ∼1.000), and was significantly better than t-tau (0.876), p-tau (0.890), hippocampal volume (0.824), and temporal cortical thickness (0.860). For prodromal AD, there were no significant AUROC differences between CSF tau and 18F-AV-1451 measures (0.836-0.939), but MRI measures had lower AUROCs (0.652-0.769).CSF tau and 18F-AV-1451 have equal performance in early clinical stages of AD, but 18F-AV-1451 is superior in the dementia stage, and exhibits close to perfect diagnostic performance for mild to moderate AD.This study provides Class III evidence that CSF tau and 18F-AV-1451 PET have similar performance in identifying early AD, and that 18F-AV-1451 PET is superior to CSF tau in identifying mild to moderate AD.
|
|
| 2. |
- Smith, Ruben, et al.
(författare)
-
In vivo retention of (18)F-AV-1451 in corticobasal syndrome.
- 2017
-
Ingår i: Neurology. - 1526-632X. ; 89:8, s. 845-853
-
Tidskriftsartikel (refereegranskat)abstract
- To study the usefulness of (18)F-AV-1451 PET in patients with corticobasal syndrome (CBS).We recruited 8 patients with CBS, 17 controls, 31 patients with Alzheimer disease (AD), and 11 patients with progressive supranuclear palsy (PSP) from the Swedish BioFINDER study. All patients underwent clinical assessment, (18)F-AV-1451 PET, MRI, and quantification of β-amyloid pathology. A subset of participants also underwent (18)F-FDG-PET.In the 8 patients with CBS, 6 had imaging findings compatible with the corticobasal degeneration pathology and 2 with typical AD pathology. In the 6 patients with CBS without typical AD pathology, there were substantial retentions of (18)F-AV-1451 in the motor cortex, corticospinal tract, and basal ganglia contralateral to the most affected body side. These patients could be clearly distinguished from patients with AD dementia or PSP using (18)F-AV-1451. However, cortical atrophy was more widespread than the cortical retention of (18)F-AV1451 in these CBS cases, and cortical AV-1451 uptake did not correlate with cortical thickness or glucose hypometabolism. These results are in sharp contrast to AD dementia, where (18)F-AV-1451 retention was more widespread than cortical atrophy, and correlated well with cortical thickness and hypometabolism.Patients with CBS without typical AD pathology exhibited AV-1451 retention in the motor cortex, corticospinal tract, and basal ganglia contralateral to the affected body side, clearly different from controls and patients with AD dementia or PSP. However, cortical atrophy measured with MRI and decreased (18)F-fluorodeoxyglucose uptake were more widespread than (18)F-AV-1451 uptake and probably represent earlier, yet less specific, markers of CBS.This study provides Class III evidence that (18)F-AV-1451 PET distinguishes between CBS and AD or PSP.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 6. |
- Ossenkoppele, Rik, et al.
(författare)
-
Discriminative Accuracy of F-18 flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders
- 2018
-
Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 320:11, s. 1151-1162
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The positron emission tomography (PET) tracer [F-18]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [F-18]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-beta [A beta]positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders). EXPOSURES The index testwas the [F-18]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls. MAIN OUTCOMES AND MEASURES The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [F-18]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [F-18]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [F-18]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined. RESULTS Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-beta positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [F-18]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6%(95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8%(95% CI, 92.0%-99.1%) sensitivity and 87.9%(95% CI, 81.9%-92.4%) specificity using the Youden Index-derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [F-18]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P<.001). Diagnostic performance of the 5 [F-18]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84). CONCLUSIONS AND RELEVANCE Among patients with established diagnoses at a memory disorder clinic, [F-18]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.
|
|
| 7. |
|
|
| 8. |
-
Larmar och gör sig till
- 2017
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Larmrapporterna duggar tätt inom flera delar av samhället idag och en turbulent omvärld gör sig ständigt påmind. I en tid där den som hörs och syns mest oftast är den som får fram sitt budskap syftar Larmar och gör sig till till att ge diverse effektfulla och känsloknutna utsagor om vår samtid lite empiriskt tuggmotstånd. Larmar och gör sig till är den sjuttionde forskarantologin från SOM-institutet. Boken innehåller 40 kapitel och baseras i huvudsak på 2016 års nationella SOM-undersökning, i kombination med SOM-institutets trettioåriga tidsserier.
|
|
| 9. |
- Ramdas, S., et al.
(författare)
-
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
|
|
| 10. |
- Wedeking, Daniela, et al.
(författare)
-
The influence of arm and ski pole during alpine skiing
- 2019
-
Konferensbidrag (refereegranskat)abstract
- INTRODUCTION: Research investigating the correlation between impairment and key performance indicators in para-alpine skiing is needed for a future evidence based classification system (Tweedy and Vanlandewijck 2011). Only a little research in para-alpine skiing exists, especially in the standing classes LW5/7 and LW6/8 (impairment of one or two arms). The use of arms and poles affects performance in alpine skiing[OM1] but how underlying biomechanical parameters as kinematics and kinetics are related to performance has to the authors knowledge not been studied before.PURPOSE: The purpose of this study was to further the understanding of slalom skiing with two ski poles, one pole or without poles (c2, c1, c0) by investigating the biomechanical differences (kinematics and foot plantar pressure) for able-bodied athletes.METHODS: Ten able-bodied right-handed junior skiers on national level were tested in three conditions - c0, c1, c2, while skiing a slalom course (28 gates, 62 m vertical drop). 3D kinematic data were collected at 200 Hz by 12 inertial motion units (Myomotion, Noraxon Inc, USA) placed on head, trunk, pelvis, arms and legs. Ski-time was measured with timing gates (XS Crystal Synchronization, Brower Timing Systems, USA) and kinetics were measured with pressure insoles (Pedar, Novel GmbH, Germany) placed inside each ski boot. Normal ground reaction force (nGRF) and relative force time integrals (relFTI) were calculated according to Melai et. Al (2011). Kinematics and plantar pressure were analysed over three right and left turns and averaged for each condition. Right turn and left turn were distinguished at the time point where the shank was standing vertical.RESULTS: Time analysis showed that time increased with the use of less ski poles, mean difference between c1c2 of 1.27 ± 1.69 s (p=0.001) and between c0c1 of 0.73 ± 1.95 s (p=0.003[OM2] ). Kinematic analysis showed that different approaches were used to attack a slalom gate in condition c1 and c0, for example slalom-attack, giant slalom attack or opposite arm attack. Interquartile range and median of the body angles [OM3] differed between conditions, e.g. lower median (indicate less deviation from anatomical basic position[OM4] ) in c0 and mostly lower than in c1 and c2. Furthermore, relFTI was related to the turning side (right or left turn) and showed largest asymmetry for condition c1.CONCLUSION: Reduced balance due to missing ski pole/s lead to compensatory movements in the upper body and asymmetry in foot plantar pressure. This reduced the ability for a controlled turn. Whether or not only reduced balance or also the skiers low experience of skiing with reduced number of poles influenced the performance remains unclear.REFERENCESMelai, Tom, T. Herman IJzerman, Nicolaas C. Schaper, Ton L.H. de Lange, Paul J.B. Willems, Kenneth Meijer, Aloysius G. Lieverse, and Hans H.C.M. Savelberg. 2011. ‘Calculation of Plantar Pressure Time Integral, an Alternative Approach’. Gait & Posture 34 (3): 379–83. https://doi.org/10.1016/j.gaitpost.2011.06.005.Tweedy, S. M., and Y. C. Vanlandewijck. 2011. ‘International Paralympic Committee Position Stand--Background and Scientific Principles of Classification in Paralympic Sport’. British Journal of Sports Medicine 45 (4): 259–69. https://doi.org/10.1136/bjsm.2009.065060.
|
|
