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| 4. |
- Aguilar, C., et al.
(författare)
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Automated CT-based segmentation and quantification of total intracranial volume
- 2015
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 25:11, s. 3151-3160
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Materials and methods Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. Results We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 x tICVml[automated] - 33.78 (R-2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. Conclusions tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.
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| 5. |
- Cavallin, L, et al.
(författare)
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Can dynamic susceptibility contrast magnetic resonance imaging replace single-photon emission computed tomography in the diagnosis of patients with Alzheimer's disease? A pilot study
- 2006
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:9, s. 977-985
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Material and Methods: Twenty-four patients, eight with AD, 10 with MCI, and six controls were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with gadobutrol. Three observers performed a visual interpretation of the SPECT and MR images using a four-point visual scale. Results: SPECT was superior to DSC-MRI in differentiating normal from pathological. All three observers showed statistically significant results in discriminating between the control group, AD, and MCI by SPECT, with a P value of 0.0006, 0.04, and 0.01 for each observer. The statistical results were not significant for MR ( P values 0.8, 0.1, and 0.2, respectively). Conclusion: DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer's disease. Several patient- and method-related improvements should be made before this method can be recommended for clinical practice.
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| 6. |
- Cavallin, L, et al.
(författare)
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Overtime reliability of medial temporal lobe atrophy rating in a clinical setting
- 2012
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 53:3, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- Medial temporal lobe atrophy (MTA) is one of the first magnetic resonance imaging (MRI) signs in patients with Alzheimer's disease (AD) and used as a measure of disease progression. Visual assessment of MTA is easy to perform but the reliability of MTA rating over time has not been studied. Purpose To investigate what happens to the MTA rating scores if two radiologists rate the same MRI scans six times over a period of 1 year. Material and Methods One hundred outpatients were included in this study. All patients underwent MRI with a protocol and sequences used for geriatric patients, according to local clinical standards. One neuroradiologist and one general radiologist independently of each other performed retrospective visual assessments of MTA six times, using the same scans, over a period of 1 year. Results Intra-rater kappa varied between κ 0.65 and 0.84 for the neuroradiologist and κ 0.38 and 0.74 for the general radiologist. Intra-rater weighted kappa (wκ) values showed almost perfect agreement for both investigators (wκ 0.83–0.94). Inter-rater reliability showed fair to moderate agreement, with the kappa value varying from κ 0.29 to 0.48 and weighted kappa values ranging from wκ 0.72 to 0.84. There was a statistically significant difference in rating between the two investigators. Conclusion Visual assessment of MTA repeated over time has a high grade of reproducibility when performed by an experienced investigator. The reproducibility drops when assessment is rarely performed. Inter-rater reliability is low when two investigators not working together are compared.
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| 7. |
- Cavallin, L, et al.
(författare)
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Voxel-based correlation between coregistered single-photon emission computed tomography and dynamic susceptibility contrast magnetic resonance imaging in subjects with suspected Alzheimer disease
- 2008
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:10, s. 1154-1161
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current diagnosis of Alzheimer disease is made by clinical, neuropsychologic, and neuroimaging assessments. Neuroimaging techniques such as magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) could be valuable in the differential diagnosis of Alzheimer disease, as well as in assessing prognosis. Purpose: To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). Material and Methods: 24 patients, eight with AD, 10 with MCI, and six controls, were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO, Ceretec; GE Healthcare Ltd., Little Chalsont UK) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a contrast-enhancing gadobutrol formula (Gadovist; Bayer Schering Pharma, Berlin, Germany). Voxel-based correlation between coregistered SPECT and DSC-MR images was calculated. Region-of-interest (ROI) analyses were then performed in 24 different brain areas using brain registration and analysis of SPECT studies (BRASS; Nuclear Diagnostics AB, Stockholm, Sweden) on both SPECT and DSC-MRI. Results: Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. ROI analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and five regions in DSC-MR. Conclusion: SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer disease.
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| 9. |
- Oksengard, A. R., et al.
(författare)
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Lack of Accuracy for the Proposed 'Dubois Criteria' in Alzheimer's Disease: A Validation Study from the Swedish Brain Power Initiative
- 2010
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 30:4, s. 374-380
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Our purpose was to investigate whether the new research criteria for Alzheimer's disease proposed in 2007 by Dubois et al. are valid in a naturalistic memory clinic sample. Method: Retrospective diagnostic analyses were carried out to compare the traditional diagnostic criteria for dementia with the new criteria suggested by Dubois et al. No patient had gone through all procedures postulated as additional features in the proposed new Dubois criteria. Material: Two independent experienced geriatricians re-examined 150 complete patients' records. The study physicians were blinded to any of the results of the core and additional features suggested by Dubois et al. to avoid circular diagnostic bias. Results: Among our 96 patients with a clinical diagnosis of subjective cognitive impairment and/or mild cognitive impairment, 2 of the patients with subjective cognitive impairment and 5 patients with mild cognitive impairment would classify as pre-dementia Alzheimer's disease according to the Dubois criteria. In our 23 Alzheimer patients diagnosed clinically, only 12 of the cases fulfilled the criteria for Alzheimer's disease suggested by Dubois et al. Interpretation: The proposed new criteria for Alzheimer's disease are valid in 55% of our patients clinically diagnosed as having full-blown Alzheimer dementia. Additionally, 7.3% 'true' Alzheimer cases will be identified in a group of 96 clinically non-demented patients. Our results show that there is a large heterogeneity in a clinical naturalistic sample of patients with an Alzheimer phenotype. Conclusion: There is a need to further validate the currently existing biomarkers in large unselected samples and avoid the pitfall of workup bias and circular diagnostic processes. Additionally, valid age-specific cut-off values for the diagnostic markers in question have to be defined. Copyright (C) 2010 S. Karger AG, Basel
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| 10. |
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| 11. |
- Wahlund, L. O., et al.
(författare)
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Imaging biomarkers of dementia: recommended visual rating scales with teaching cases
- 2017
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 8:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- The diagnostic work up of dementia may benefit from structured reporting of CT and/or MRI and the use of standardised visual rating scales. We advocate a more widespread use of standardised scales as part of the workflow in clinical and research evaluation of dementia. We propose routine clinical use of rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA) and white matter hyperintensities (WMH). These scales can be used for evaluation of both CT and MRI and are efficient in routine imaging assessment in dementia, and may improve the accuracy of diagnosis. Our review provides detailed imaging examples of rating increments in each of these scales and a separate teaching file. The radiologist should relate visual ratings to the clinical assessment and other biomarkers to assist the clinician in the diagnostic decision.
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| 12. |
- Beyer, J., et al.
(författare)
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Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:4, s. 878-888
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Forskningsöversikt (refereegranskat)abstract
- In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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| 13. |
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| 14. |
- Björkholm, Magnus, et al.
(författare)
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Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:6, s. 1085-1089
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.
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| 15. |
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| 16. |
- Cedres, N, et al.
(författare)
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Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer's Disease
- 2021
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 20:4, s. 153-164
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer’s Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]). <b><i>Methods:</i></b> A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and <i>APOE</i> genotype. <b><i>Results:</i></b> Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N− profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T−N− or A+T−N+ profiles clustered together and were mainly from KIDS. <i>APOE</i> ε4 carriers more frequently showed the A+T−N− and A+T+N− profiles. <b><i>Conclusions:</i></b> Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.
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| 17. |
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| 18. |
- Enache, D, et al.
(författare)
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Medial temporal lobe atrophy and depressive symptoms in elderly patients with and without Alzheimer disease
- 2015
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Ingår i: Journal of geriatric psychiatry and neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 28:1, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether depressive symptoms are associated with medial temporal lobe atrophy in older people with and without Alzheimer disease (AD).Method:A total of 368 memory clinic patients with AD, mild cognitive impairment, and subjective cognitive impairment (SCI) were included. Depressive symptoms were defined as a score of 8 or higher on Cornell Scale for Depression in Dementia or use of antidepressant medications. Magnetic resonance imaging and computer tomography scans were rated for medial temporal lobe atrophy (MTA), using the Scheltens scale. For a subsample (n = 57 patients), hippocampal volume was manually traced.Results:Based on visual assessment, AD patients with depressive symptoms had less atrophy of the right medial temporal lobe (odds ratio [OR] for having MTA: 0.39; 95% confidence interval [CI] 0.16-0.99) and decreased scores on Scheltens scale for the left medial temporal lobe (OR: 0.43, 95% CI 0.19-0.96) in comparison to AD patients without depressive symptoms. In the subgroup where manual tracing was used to measure hippocampal volume, people with SCI experiencing depressive symptoms had smaller right (mean difference: 0.28 cm3; P = .005) and left (mean difference 0.32 cm3; P = .002) hippocampal volumes compared to people with SCI who did not have depressive symptoms.Conclusion:Hippocampal atrophy was more pronounced among patients having SCI with depressive symptoms, while the medial temporal lobe was less atrophic in patients having AD with depressive symptoms than those without depressive symptoms. These findings suggest that different mechanisms underlie depression in older people with and without AD and may explain some of the inconsistent observations in previous studies.
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| 19. |
- Ferreira, D, et al.
(författare)
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Distinct subtypes of Alzheimer's disease based on patterns of brain atrophy: longitudinal trajectories and clinical applications
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 46263-
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Tidskriftsartikel (refereegranskat)abstract
- Atrophy patterns on MRI can reliably predict three neuropathological subtypes of Alzheimer’s disease (AD): typical, limbic-predominant, or hippocampal-sparing. A method to enable their investigation in the clinical routine is still lacking. We aimed to (1) validate the combined use of visual rating scales for identification of AD subtypes; (2) characterise these subtypes at baseline and over two years; and (3) investigate how atrophy patterns and non-memory cognitive domains contribute to memory impairment. AD patients were classified as either typical AD (n = 100), limbic-predominant (n = 33), or hippocampal-sparing (n = 35) by using the Scheltens’ scale for medial temporal lobe atrophy (MTA), the Koedam’s scale for posterior atrophy (PA), and the Pasquier’s global cortical atrophy scale for frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n = 30). 230 healthy controls were also included. There was great overlap among subtypes in demographic, clinical, and cognitive variables. Memory performance was more dependent on non-memory cognitive functions in hippocampal-sparing and the no atrophy group. Hippocampal-sparing and the no atrophy group showed less aggressive disease progression. Visual rating scales can be used to identify distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating scales may facilitate investigation of AD heterogeneity in clinical routine.
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| 20. |
- Ferreira, D, et al.
(författare)
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Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers
- 2016
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 42:1-2, s. 80-92
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. <b><i>Methods:</i></b> A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. <b><i>Results:</i></b> qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. <b><i>Conclusion:</i></b> Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.
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| 26. |
- Osby, E, et al.
(författare)
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CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 101:10, s. 3840-3848
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to test the hypothesis that administration of granulocyte colony-stimulating factor (G-CSF; filgrastim) during induction chemotherapy with CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) or CNOP (doxorubicin replaced with mitoxantrone) in elderly patients with aggressive non-Hodgkin lymphoma (NHL) improves time to treatment failure (TTF), complete remission (CR) rate, and overall survival (OS). Furthermore, the efficacy of CHOP versus CNOP chemotherapy was compared. A total of 455 previously untreated patients older than 60 years with stages 11 to IV aggressive NHL were included-in the analysis. Patients (median age, 71 years; range, 60-86 years) were randomized to receive CHOP (doxorubicin 50 mg/m(2)) or CNOP (mitoxantrone 10 mg/m(2)) with or without G-CSIF (5 mug/kg from day 2 until day 10-14 of each cycle every 3 weeks; 8 cycles). Forty-seven patients previously hospitalized for class I to 11 congestive heart failure were randomized to receive CNOP with or without G-CSF (not included in the CHOP versus CNOP analysis). The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same, 52%, and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups, 60% and 43% (P < .001), respectively. No benefit of G-CSF in terms of TTF and OS could be shown (P = .96 and P = .22, respectively), whereas CHOP was superior to CNOP (TTF/OS P < .001). The incidences of severe granulocytopenia (World Health Organization grade IV) and granulocytopenic infections were higher in patients not receiving G-CSF The cumulative proportion of patients receiving 90% or more of allocated chemotherapy was higher (P < .05) in patients receiving G-CSF. Concomitant G-CSF treatment did not improve CR rate, TTF, or OS. Patients receiving CHOP fared better than those given CNOP chemotherapy. The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy. (C) 2003 by The American Society of Hematology.
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| 29. |
- Persson, K, et al.
(författare)
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Comparison of automated volumetry of the hippocampus using NeuroQuant® and visual assessment of the medial temporal lobe in Alzheimer's disease
- 2018
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 59:8, s. 997-1001
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Tidskriftsartikel (refereegranskat)abstract
- Different clinically feasible methods for evaluation of medial temporal lobe atrophy exists and are useful in diagnostic work-up of Alzheimer’s disease (AD). Purpose To compare the diagnostic properties of two clinically available magnetic resonance imaging (MRI)-based methods—an automated volumetric software, NeuroQuant® (NQ) (evaluation of hippocampus volume) and the Scheltens scale (visual evaluation of medial temporal lobe atrophy [MTA])—in patients with AD dementia, and subjective and mild cognitive impairment (non-dementia). Material and Methods MRIs from 56 patients (31 AD, 25 non-dementia) were assessed with both methods. Correlations between the methods were calculated and receiver operating curve (ROC) analyses that yield area under the curve (AUC) statistics were conducted. Results High correlations were found between the two MRI assessments for the total hippocampal volume measured with NQ and mean MTA score (–0.753, P < 0.001), for the right (–0.767, P < 0.001), and for the left (–0.675, P < 0.001) sides. The NQ total measure yielded somewhat higher AUC (0.88, “good”) compared to the MTA mean measure (0.80, “good”) in the comparison of patients with AD and non-dementia, but the accuracy was in favor of the MTA scale. Conclusion The two methods correlated highly and both methods reached equally “good” power.
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| 30. |
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| 31. |
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| 32. |
- Persson, K, et al.
(författare)
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Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease
- 2017
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 44:1-2, s. 12-24
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). <b><i>Methods:</i></b> vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE ɛ4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. <b><i>Results:</i></b> vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (<i>p</i> = 0.075), where delayed recall and APOE ɛ4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. <b><i>Conclusion:</i></b> In adjusted models, memory function, APOE ɛ4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia.
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| 33. |
- Rutqvist, L E, et al.
(författare)
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A systematic overview of radiation therapy effects in breast cancer
- 2003
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 532-545
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Tidskriftsartikel (refereegranskat)abstract
- A systematic review of radiation therapy trials in several turnout types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41204 patients. The results were compared with those of a similar overview from 1996 including 285982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the turnout bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.
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| 34. |
- Schmitz, N., et al.
(författare)
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CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:5, s. 1267-1273
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Tidskriftsartikel (refereegranskat)abstract
- To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma. We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) +/- etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved. Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit. In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.
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- Shams, M, et al.
(författare)
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MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment
- 2022
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Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14, s. 897674-
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.Material and MethodsThis is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.ResultsApolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid β (Aβ) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05).ConclusionApolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aβ42 plaque formation in the brain, as reflected by decreased CSF Aβ42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.
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- Trkulja, C. L., et al.
(författare)
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Rational antibody design for undruggable targets using kinetically controlled biomolecular probes
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:16
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Tidskriftsartikel (refereegranskat)abstract
- Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics-sensitive druggability probes in native-state and disease-relevant proteins. By using low-Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal antibodies targeting the transient receptor potential vanilloid 1 (TRPV1) channel, a clinically validated pain target widely considered undruggable with antibodies, and apoptosis-inducing antibodies selectively mediating cytotoxicity in KRAS-mutated cells. It is our hope that this platform will widen the scope of antibody therapeutics for the benefit of patients.
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| 45. |
- Velickaite, Vilma, et al.
(författare)
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Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort : gender-corrected and education-corrected normative data
- 2018
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:4, s. 1739-1747
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.
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