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Träfflista för sökning "WFRF:(Riklund Katrine MD PhD Professor 1963 ) "

Sökning: WFRF:(Riklund Katrine MD PhD Professor 1963 )

  • Resultat 1-10 av 28
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  • Kockum, Karin, 1981- (författare)
  • Imaging in Idiopathic Normal Pressure Hydrocephalus : The value of structured radiological evaluation
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological condition where the symptoms include disturbed gait, balance, cognition and continence. The diagnostic guidelines are based on typical symptoms combined with imaging showing enlarged ventricles. Several scales for evaluating symptoms exist, but no corresponding tool is in use for imaging. The aim of this thesis was to construct a radiological scoring system, the iNPH Radscale, to facilitate radiological evaluation and systematic reporting of changes. Further, to test the reliability and accuracy of the scale and evaluate the usefulness for longitudinal monitoring.Methods: In paper I 168 individuals over 65 years of age from the general population underwent computed tomography (CT) of the brain and a neurological examination, and the same cohort was followed up 2 years later in paper IV. The iNPH Radscale was developed in these papers and further validated in papers II and III. Papers II and III included surgically treated iNPH patients with preoperative imaging of the brain. Thirty-five patients were included in paper II comparing preoperative CT and magnetic resonance imaging (MRI) using the iNPH Radscale. Paper III included 75 shunt responsive patients and 55 asymptomatic controls to evaluate the accuracy of the iNPH Radscale.Results: In paper I, seven parameters summarized as a total iNPH Radscale score were significantly associated with clinical iNPH symptoms (r = 0.55, p < 0.001). In paper II, the agreement between CT and MRI was substantial to almost perfect (kappa and intraclass correlation, 0.60–0.91, p < 0.001) for all parameters except periventricular white matter changes. In paper III the iNPH Radscale score was significantly higher in the iNPH group than the control group (p <0.001). Receiver operating characteristics analysis yielded an area under the curve of 99.7 %, and an iNPH Radscale score £ 4 identified those without iNPH (sensitivity 100 %, specificity 96 % and overall accuracy 98.5 %). In paper IV, symptomatic participants had significantly higher iNPH Radscale scores at baseline and follow-up.Conclusions: The iNPH Radscale summarizes seven imaging features from the diagnostic guidelines and is applicable to both CT and MRI. INPH is very likely in patients with an iNPH Radscale score ³ 8 and corresponding clinical symptoms. On the other hand, the diagnosis should be questioned when the iNPH Radscale score is less than the cut-off of 4. In summary, the iNPH Radscale may become a relevant diagnostic tool for standardized evaluation in the workup of patients with suspected iNPH, as a diagnostic checklist and as a screening tool for detection with the potential for ruling out the disease.
  • Strandberg, Sara, 1976- (författare)
  • 11C-Acetate-PET/CT in Primary Staging of High-Risk Prostate Cancer
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Prostate cancer (PC) is the second most common cancer in men worldwide, affecting ~12%. Although most are clinically insignificant low-risk cancers, the more aggressive high-risk cancers require correct staging, prior to curative radiotherapy or surgery. Standard staging procedures and tools include clinical examination, estimated nomogram risk of pelvic lymph node (LN) metastases, and bone scintigraphy (BS). Additional staging information can be obtained with magnetic resonance imaging (MRI), computed tomography (CT) and positron-emission tomography/computed tomography (PET/CT). PET/CT can provide information on both functional and morphological changes.The aims of the present thesis were to investigate the diagnostic and prognostic value of 11C-acetate (ACE)-PET/CT in high-risk PC, and to optimize the ACE-PET protocol. In study I and II, higher detection rates of LN metastases and bone metastases were found with ACE-PET/CT, than with standard methods nomogram risk and BS. The higher ACE uptake in the prostate (prostate lipogenic tumor burden), the higher the risk of suspected LN metastases (N+ disease) on PET/CT. ACE-PET/CT findings correlated better than BS with follow-up data, and influenced therapy in 11-43%. In study III, PET reconstruction algorithm with resolution recovery showed more accurate functional tumor volumes compared to CT, and higher measurements of lipogenic activity, than reconstruction algorithm without resolution recovery. Study IV was part of an interventional radiotherapy study (PARAPLY) on high-risk PC, with addition of image-guided simultaneous integrated boost to delineated prostate tumors and pelvic LN metastases reported in ACE-PET/CT and MRI. Comparative analyses of clinical risk parameters and baseline ACE-PET/CT parameters showed significant associations between nomogram risk and prostate lipogenic tumor burden, between N+ disease on PET/CT and prostate lipogenic tumor burden, but surprisingly not between nomogram risk and N+ disease on PET/CT. PET with resolution recovery was superior in detection of N+ disease.In conclusion, ACE-PET/CT showed a higher detection rate of suspected metastases compared to standard methods clinical nomogram and BS, in high-risk PC. PET reconstruction with resolution recovery seems to improve the diagnostic added value of ACE-PET/CT. Prostate lipogenic tumor burden could serve as a predictor of N+ disease. The prognostic value of ACE-PET/CT remains to be investigated in future studies.
  • Vikner, Tomas, et al. (författare)
  • Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults
  • 2021
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:7, s. 1778-1790
  • Tidskriftsartikel (refereegranskat)abstract
    • Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocampal volume. However, evidence linking features of the cerebral arterial flow waveform to hippocampal function is lacking. We used a high-resolution 4D flow MRI approach to estimate global representations of the time-resolved flow waveform in distal cortical arteries and in proximal arteries feeding the brain in healthy older adults. Waveform-based clustering revealed a group of individuals featuring steep systolic onset and high amplitude that had poorer hippocampus-sensitive episodic memory (p = 0.003), lower whole-brain perfusion (p = 0.001), and weaker microvascular low-frequency oscillations in the hippocampus (p = 0.035) and parahippocampal gyrus (p = 0.005), potentially indicating compromised neurovascular unit integrity. Our findings suggest that aberrant hemodynamic forces contribute to cerebral microvascular and hippocampal dysfunction in aging.
  • Ahlén Bergman, Emma, et al. (författare)
  • Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
  • 2018
  • Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
  • Björeland, Ulrika, et al. (författare)
  • Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy
  • 2021
  • Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 17, s. 117-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.Materials and methods: Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.Results: At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.Conclusions: Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.
  • Bäckström, David C, M.D. 1978-, et al. (författare)
  • NfL as a biomarker for neurodegeneration and survival in Parkinson disease
  • 2020
  • Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 95:7, s. e827-e838
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).METHODS: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.
  • de Boer, Lieke, et al. (författare)
  • Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning
  • 2020
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280
  • Tidskriftsartikel (refereegranskat)abstract
    • Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.
  • Karalija, Nina, 1984-, et al. (författare)
  • A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging
  • 2021
  • Ingår i: NeuroImage. - : Academic Press. - 1053-8119 .- 1095-9572. ; 245
  • Tidskriftsartikel (refereegranskat)abstract
    • Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
  • Karalija, Nina, 1984-, et al. (författare)
  • Cardiovascular factors are related to dopamine integrity and cognition in aging
  • 2019
  • Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.
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