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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 4. |
- F., Durmo, et al.
(författare)
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Multivoxel 1H MR spectroscopy biometrics for preoprerative differentiation between brain tumors
- 2018
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 60:S2, s. 444-444
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Konferensbidrag (refereegranskat)abstract
- Purpose To investigate multivoxel proton Magnetic Resonance Spectroscopy (1HMRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-(LGG) and high grade glioma (HGG). Methods Thirty-five patients (15 HGG, 9 LGG and 11 MET) were included. Proton Magnetic Resonance Spectroscopy Imaging(1H-MRSI) data was assessed and neurochemical profiles for metabolites (NAA+NAAG, Cr+PCr, Glu+Gln (Glx), Lac, Ins, GPC+PCho) and total Lipids (tLip) and macromolecule (tMM) signals were estimated. Concentrations were reported as either absolute or ratios to total choline (tCho=GPC+PCho) and creatine (tCr=Cr+PCr) levels. Voxels of interest (VOIs) in a MRSI matrix were labelled accordingly to contrast-enhancing/nonenhancing lesional, edema, ipsi- or contralateral healthy appearing tissue and the metabolite averages were reported for each tissue type. Multi-biometric analysis with logistic regression, ROC- and Kaplan-Meier survival analysis was performed in SPSS v.24 and postprocessing with LC Model. Results Across HGG/LGG/MET; the average Ins/tCho was shown to be prognostic for overall survival (OS): with low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (Log Rank
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- F., Durmo, et al.
(författare)
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Mutlimodality MR imaging for differentiation between brain tumor lesions
- 2016
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 58:Suppl 1, s. 53-54
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Konferensbidrag (refereegranskat)abstract
- Purpose: Applying diffusion and perfusion metrics for evaluation of low-(LGG), high grade glioma (HGG) and metastases (MET) for differential diagnosis. Materials and Method: 43 patients (18HGG, 10 LGG, and 15MET) were included. MR data for tumour volume, perilesional edema, rCBF-, rCBV-, FLAIR-, FA-, ADC-maps were quantified by regions of interest (ROI). Measures of different parameters, and ratios, using contralateral white matter as denominator, were performed. A binary logistic regression model was constructed for multi-parametric analysis and ROCanalysis. Results: Significant difference was found for nADCt, rCBF, rCBV between LGG and HGG, nADCe between HGG and MET, and Ev, Ev-Tv ratio, nADCt, nADCe, rCBF, rCBV between LGG and MET. ROCanalysis for HGG compared to LGG showed 80 % sensitivity and 81.2 % specificity for nADCt, 100 % sensitivity and 100 % specificity for rCBF and 80 % sensitivity and 90 % specificity for rCBV. ROC-curves betweenMETand LGG showed sensitivity and specificity for Ev 73.3 % and 90 %, Ev-Tv ratio 80 % and 100 %, nADCt 90 % and 86.7 %, nADCe 80 % and 90 %, rCBF 93.3 % and 100 %, and rCBV 60 % and 100 %. Combining Ev, Ev-Tv ratio, nADCt, nADCe and rCBV between METand LGG gave 93.3%sensitivity and 100%specificity. Combining nADCt and rCBV between HGG and LGG 86.7 % sensitivity and 100 % specificity. Conclusion: Multi-parametric imaging protocols is an advantage for preoperative distinction of LGG, HGG and MET.
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- Malmstrom, A., et al.
(författare)
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GENDER DIFFERENCES IN GLIOMA - FINDINGS FROM THE SWEDISH NATIONAL QUALITY REGISTRY FOR PRIMARY BRAIN TUMORS
- 2018
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 20, s. 267-267
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundAn often debated topic in neuro-oncology are the differences in incidence and survival between men and women with glioma. To the Swedish National Quality Registry for Primary Brain Tumors (SNQR) over 90% of all Swedish patients with primary brain tumor have been reported since 1999. We therefore conducted a study of clinical factors in relation to gender in patients registered with high grade glioma using data from the SNQR.MethodsThe SNQR was searched for patients diagnosed with high grade glioma from 1999 through 2016 and clinical data were analyzed for gender differences regarding prognostic factors, tumor location and survival.ResultsIn all 5470 patients were identified, 2268 women and 3202 men, giving a ratio of 1:1.4. We found a survival benefit for women when analyzing the whole time period. While there was no difference in median survival (315 versus 326 days for women versus men), there were significantly more long term survivors among women, with mean survival being 742 versus 628 days (p=0.03). The survival benefit for women was also only present in those being younger than 50 years at diagnosis. We looked at the prognostic factors age, performance status (PS) and surgery in relation to gender. We found that median age for being diagnosed with high grade glioma was significantly higher in women than men (63 versus 62 years, p=0.002) and the ratio of women in relation to men increases with increasing age, the ratios for younger than 50 years being 1:1.5 and over 50 years 1:1.39. A higher fraction of the women are over 60 years when diagnosed compared to men (57% vs 53%, p=0.002). For PS we identified that significantly more women were reported to have PS 3 and for men more PS 0 was registered. For type of surgery we found no gender differences. For tumor location more women had tumors in the frontal and less in the temporal lobe as compared to men.ConclusionIn the Swedish National Quality Registry for Primary Brain Tumors we identified differences in incidence and survival between men and women related to age and also a disparity regarding PS and tumor location. If the cause of these clinical differences is due to molecular background or has other causes warrants further study.
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| 8. |
- Rydelius, A., et al.
(författare)
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Predictive value of diffusion MRI-based parametric response mapping for prognosis and treatment response in glioblastoma
- 2023
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Ingår i: Magnetic Resonance Imaging. - 0730-725X. ; 104, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of treatment response is important for the management of patients with malignant brain tumors such as glioblastoma to assure good quality of life in relation to therapeutic efficacy. Aim: To investigate whether parametric response mapping (PRM) with diffusion MRI may provide prognostic information at an early stage of standard therapy for glioblastoma. Materials and methods: This prospective study included 31 patients newly diagnosed with glioblastoma WHO grade IV, planned for primary standard postoperative treatment with radiotherapy 60Gy/30 fractions with concomitant and adjuvant Temozolomide. MRI follow-up including diffusion and perfusion weighting was performed at 3 T at start of postoperative chemoradiotherapy, three weeks into treatment, and then regularly until twelve months postoperatively. Regional mean diffusivity (MD) changes were analyzed voxel-wise using the PRM method (MD-PRM). At eight and twelve months postoperatively, after completion of standard treatment, patients were classified using conventional MRI and clinical evaluation as either having stable disease (SD, including partial response) or progressive disease (PD). It was assessed whether MD-PRM differed between patients having SD versus PD and whether it predicted the risk of disease progression (progression-free survival, PFS) or death (overall survival, OS). A subgroup analysis was performed that compared MD-PRM between SD and PD in patients only undergoing diagnostic biopsy. MGMT-promotor methylation status (O6-methylguanine-DNA methyltransferase) was registered and analyzed with respect to PFS, OS and MD-PRM. Results: Of the 31 patients analyzed: 21 were operated by resection and ten by diagnostic biopsy. At eight months, 19 patients had SD and twelve had PD. At twelve months, ten patients had SD and 20 had PD, out of which ten were deceased within twelve months and one was deceased without known tumor progression. Median PFS was nine months, and median OS was 17 months. Eleven patients had methylated MGMT-promotor, 16 were MGMT unmethylated, and four had unknown MGMT-status. MD-PRM did not significantly predict patients having SD versus PD neither at eight nor at twelve months. Patients with an above median MD-PRM reduction had a slightly longer PFS (P = 0.015) in Kaplan-Maier analysis, as well as a non-significantly longer OS (P = 0.099). In the subgroup of patients only undergoing biopsy, total MD-PRM change at three weeks was generally higher for patients with SD than for patients with PD at eight months, although no tests were performed. MGMT status strongly predicted both PFS and OS but not MD-PRM change. Conclusion: MD-PRM at three weeks was not demonstrated to be predictive of treatment response, disease progression, or survival. Preliminary results suggested a higher predictive value in non-resected patients, although this needs to be evaluated in future studies.
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