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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Verwer, E E, et al.
(författare)
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Harmonisation of PET/CT contrast recovery performance for brain studies
- 2021
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 48:9, s. 2856-2870
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed.METHODS: Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based "digital" systems) were used to acquire 30-min PET scans of a Hoffman 3D Brain phantom filled with ~ 33 kBq·mL-1 [18F]FDG. Scan data were reconstructed using various reconstruction settings. The images were rigidly coregistered to a template (voxel size 1.17 × 1.17 × 2.00 mm3) onto which several volumes of interest (VOIs) were defined. Recovery coefficients (RC) and grey matter to white matter ratios (GMWMr) were derived for eroded (denoted in the text by subscript e) and non-eroded grey (GM) and white (WM) matter VOIs as well as a mid-phantom cold spot (VOIcold) and VOIs from the Hammers atlas. In addition, left-right hemisphere differences and voxel-by-voxel differences compared to a reference image were assessed.RESULTS: Systematic differences were observed for reconstructions with and without point-spread-function modelling (PSFON and PSFOFF, respectively). Normalising to image-derived activity, upper and lower limits ensuring image comparability were as follows: for PSFON, RCGMe = [0.97-1.01] and GMWMre = [3.51-3.91] for eroded VOI and RCGM = [0.78-0.83] and GMWMr = [1.77-2.06] for non-eroded VOI, and for PSFOFF, RCGMe = [0.92-0.99] and GMWMre = [3.14-3.68] for eroded VOI and RCGM = [0.75-0.81] and GMWMr = [1.72-1.95] for non-eroded VOI.CONCLUSIONS: To achieve inter-scanner comparability, we propose selecting reconstruction settings based on RCGMe and GMWMre as specified in "Results". These proposed standards should be tested prospectively to validate and/or refine the harmonisation criteria.
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- Yaqub, S., et al.
(författare)
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Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial
- 2021
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Ingår i: Trials. - London, United Kingdom : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. Methods The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. Discussion The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness.
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- Azhar, N, et al.
(författare)
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Risk of colorectal cancer following CT-verified acute diverticulitis -a nationwide population-based cohort study
- 2020
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 22:10, s. 1406-1414
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Routine colonoscopy to exclude colorectal cancer (CRC) after CT-verified acute diverticulitis is controversial. This study aimed to compare the incidence of CRC in acute diverticulitis patients with that in the general population. METHOD: Patients with an emergency admission for diverticular disease, to any Norwegian hospital, between January 1st , 2008 and December 31st , 2010 were included through identification in the Norwegian Patient Registry using International Classification of Diseases (ICD-10) codes K57.1-9. To estimate the age-specific distribution of CT-verified acute uncomplicated diverticulitis (AUD) and acute complicated diverticulitis (ACD) in this nationwide study population, numbers from the largest Norwegian emergency hospital were used. Patients diagnosed with CRC within one year following the admission for acute diverticulitis were detected through cross-matching with the Cancer Registry of Norway. Based on both Norwegian age-specific incidence of CRC and estimated age-specific distribution of CT-verified diverticulitis, standard morbidity ratios (SMR) were calculated.RESULTS: A total of 7473 patients with emergency admissions for diverticular disease were identified (estimated CT-verified AUD n=3523, ACD n=1206), and of these 155 patients were diagnosed with CRC within one year. Eighty had a CT-verified diverticulitis at index admission (41 AUD; 51.3% and 39 ACD; 49.7%). Compared to the general population SMR was 6.6 following CT-verified AUD and 16.3 following ACD respectively.CONCLUSION: The risk of CRC is higher than in the general population, the first year after CT-verified acute diverticulitis, especially after ACD. This likely represents misdiagnosis of CRC as acute diverticulitis. Follow-up colonoscopy should be recommended to all patients admitted with acute diverticulitis.
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- Collij, L. E., et al.
(författare)
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The amyloid imaging for the prevention of Alzheimer's disease consortium: A European collaboration with global impact
- 2023
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAmyloid-beta (A beta) accumulation is considered the earliest pathological change in Alzheimer's disease (AD). The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) consortium is a collaborative European framework across European Federation of Pharmaceutical Industries Associations (EFPIA), academic, and 'Small and Medium-sized enterprises' (SME) partners aiming to provide evidence on the clinical utility and cost-effectiveness of Positron Emission Tomography (PET) imaging in diagnostic work-up of AD and to support clinical trial design by developing optimal quantitative methodology in an early AD population. The AMYPAD studiesIn the Diagnostic and Patient Management Study (DPMS), 844 participants from eight centres across three clinical subgroups (245 subjective cognitive decline, 342 mild cognitive impairment, and 258 dementia) were included. The Prognostic and Natural History Study (PNHS) recruited pre-dementia subjects across 11 European parent cohorts (PCs). Approximately 1600 unique subjects with historical and prospective data were collected within this study. PET acquisition with [F-18]flutemetamol or [F-18]florbetaben radiotracers was performed and quantified using the Centiloid (CL) method. ResultsAMYPAD has significantly contributed to the AD field by furthering our understanding of amyloid deposition in the brain and the optimal methodology to measure this process. Main contributions so far include the validation of the dual-time window acquisition protocol to derive the fully quantitative non-displaceable binding potential (BPND), assess the value of this metric in the context of clinical trials, improve PET-sensitivity to emerging A beta burden and utilize its available regional information, establish the quantitative accuracy of the Centiloid method across tracers and support implementation of quantitative amyloid-PET measures in the clinical routine. Future stepsThe AMYPAD consortium has succeeded in recruiting and following a large number of prospective subjects and setting up a collaborative framework to integrate data across European PCs. Efforts are currently ongoing in collaboration with ARIDHIA and ADDI to harmonize, integrate, and curate all available clinical data from the PNHS PCs, which will become openly accessible to the wider scientific community.
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