| 1. |
- Dybjer, Elin, et al.
(författare)
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Polygenic risk of type 2 diabetes is associated with incident vascular dementia : a prospective cohort study
- 2023
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes and dementia are associated, but it is unclear whether the two diseases have common genetic risk markers that could partly explain their association. It is also unclear whether the association between the two diseases is of a causal nature. Furthermore, few studies on diabetes and dementia have validated dementia end-points with high diagnostic precision. We tested associations between polygenic risk scores for type 2 diabetes, fasting glucose, fasting insulin and haemoglobin A1c as exposure variables and dementia as outcome variables in 29 139 adults (mean age 55) followed for 20–23 years. Dementia diagnoses were validated by physicians through data from medical records, neuroimaging and biomarkers in cerebrospinal fluid. The dementia end-points included all-cause dementia, mixed dementia, Alzheimer’s disease and vascular dementia. We also tested causal associations between type 2 diabetes and dementia through two-sample Mendelian randomization analyses. Seven different polygenic risk scores including single-nucleotide polymorphisms with different significance thresholds for type 2 diabetes were tested. A polygenic risk score including 4891 single-nucleotide polymorphisms with a P-value of <5e-04 showed the strongest association with different outcomes, including all-cause dementia (hazard ratio 1.11; Bonferroni corrected P = 3.6e-03), mixed dementia (hazard ratio 1.18; Bonferroni corrected P = 3.3e-04) and vascular dementia cases (hazard ratio 1.28; Bonferroni corrected P = 9.6e-05). The associations were stronger for non-carriers of the Alzheimer’s disease risk gene APOE ϵ4. There was, however, no significant association between polygenic risk scores for type 2 diabetes and Alzheimer’s disease. Furthermore, two-sample Mendelian randomization analyses could not confirm a causal link between genetic risk markers of type 2 diabetes and dementia outcomes. In conclusion, polygenic risk of type 2 diabetes is associated with an increased risk of dementia, in particular vascular dementia. The findings imply that certain people with type 2 diabetes may, due to their genetic background, be more prone to develop diabetes-associated dementia. This knowledge could in the future lead to targeted preventive strategies in clinical practice.
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| 2. |
- Gobom, Johan, et al.
(författare)
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Antibody-free measurement of cerebrospinal fluid tau phosphorylation across the Alzheimer's disease continuum.
- 2022
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Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by an abnormal increase of phosphorylated tau (pTau) species in the CSF. It has been suggested that emergence of different pTau forms may parallel disease progression. Therefore, targeting multiple specific pTau forms may allow for a deeper understanding of disease evolution and underlying pathophysiology. Current immunoassays measure pTau epitopes separately and may capture phosphorylated tau fragments of different length depending on the non-pTau antibody used in the assay sandwich pair, which bias the measurement.We developed the first antibody-free mass spectrometric method to simultaneously measure multiple phosphorylated epitopes in CSF tau: pT181, pS199, pS202, pT205, pT217, pT231, and pS396. The method was first evaluated in biochemically defined Alzheimer's disease and control CSF samples (n=38). All seven pTau epitopes clearly separated Alzheimer's disease from non-AD (p<0.001, AUC=0.84-0.98). We proceeded with clinical validation of the method in the TRIAD (n=165) and BioFINDER-2 cohorts (n=563), consisting of patients across the full Alzheimer's disease continuum, including also young controls (<40years), as well as patients with frontotemporal dementia and other neurodegenerative disorders.Increased levels of all phosphorylated epitopes were found in Alzheimer's disease dementia and Aβ positron emission tomography-positive patients with mild cognitive impairment compared with Aβ-negative controls. For Alzheimer's disease dementia compared with Aβ-negative controls, the best biomarker performance was observed for pT231 (TRIAD: AUC=98.73%, fold change=7.64; BioFINDER-2: AUC=91.89%, fold change=10.65), pT217 (TRIAD: AUC=99.71%, fold change=6.33; BioFINDER-2: AUC=98.12%, fold change=8.83) and pT205 (TRIAD: AUC=99.07%, fold change=5.34; BioFINDER-2: AUC=93.51%, fold change=3.92). These phospho-epitopes also discriminated between Aβ-positive and Aβ-negative cognitively unimpaired individuals: pT217 (TRIAD: AUC=83.26, fold change=2.39; BioFINDER-2: AUC=91.05%, fold change=3.29), pT231 (TRIAD: AUC=86.25, fold change=3.80; BioFINDER-2: AUC=78.69%, fold change=3.65) and pT205 (TRIAD: AUC=71.58, fold change=1.51; BioFINDER-2: AUC=71.11%, fold change=1.70).While an increase was found for all pTau species examined, the highest fold change in Alzheimer's disease was found for pT231, pT217 and pT205. Simultaneous antibody-free measurement of pTau epitopes by mass spectrometry avoids possible bias caused by differences in antibody affinity for modified or processed forms of tau, provides insights into tau pathophysiology and may facilitate clinical trials on tau-based drug candidates.
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| 3. |
- Lind, Leili, et al.
(författare)
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Old-and With Severe Heart Failure: Telemonitoring by Using Digital Pen Technology in Specialized Homecare: System Description, Implementation, and Early Results
- 2016
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Ingår i: Computers, Informatics, Nursing. - : Lippincott Williams & Wilkins. - 1538-2931 .- 1538-9774. ; 34:8, s. 360-368
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Tidskriftsartikel (refereegranskat)abstract
- Telehealth programs for heart failure have been studied using a variety of techniques. Because currently a majority of the elderly are nonusers of computers and Internet, we developed a home telehealth system based on digital pen technology. Fourteen patients (mean age, 84 years [median, 83 years]) with severe heart failure participated in a 13-month pilot study in specialized homecare. Participants communicated patient-reported outcome measures daily using the digital pen and health diary forms, submitting a total of 3 520 reports. The reports generated a total of 632 notifications when reports indicated worsening health. Healthcare professionals reviewed reports frequently, more than 4700 times throughout the study, and acted on the information provided. Patients answered questionnaires and were observed in their home environment when using the system. Results showed that the technology was accepted by participants: patients experienced an improved contact with clinicians; they felt more compliant with healthcare professionals advice, and they felt more secure and more involved in their own care. Via the system, the healthcare professionals detected heart failure-related deteriorations at an earlier stage, and as a consequence, none of the patients were admitted into hospital care during the study.
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| 4. |
- Lind, Leili, et al.
(författare)
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Preliminary results of a telemonitoring study: COPD and heart failure patients exhibit great difference in their need of health care
- 2015
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Ingår i: European Respiratory Journal. - : European Respiratory Society. ; , s. PA2790-PA2790
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Growing populations of elderly patients with advanced stages of COPD or heart failure (HF) urge the need for specialized health care in the patients' home. A telemonitoring study has been initiated including patients using digital pens. Health care was provided by the specialized home care unit at a university hospital. Through an IT system the staff checked all daily patient reports. We hypothesized that the two groups of patients, advanced COPD or HF, would exhibit differences regarding exacerbations and the need of health care.Objective: To study exacerbations of COPD or HF, and patient health care consumption.Methods: A tele-monitoring system, the Health diary, which is based on digital pen technology, was employed. Exacerbations were identified using information provided through the telemonitoring system. Consumed health care was assessed as the number of patient contacts (home visits or telephone consultations).Results: Presently, 33 patients with advanced disease are enrolled (13 COPD and 20 HF patients) of which 11 patients (6 COPD and 5 HF patients) have completed the 1-yr study period or have died during the study period (2 COPD and 4 HF patients). Exacerbations were 2.8 and 0.8 and patient contacts were 96 and 42 per COPD and HF patient, respectively. While HF patients were significantly older than COPD patients, the two groups demonstrated no difference regarding gender distribution and comorbidity.Conclusions: COPD patients exhibit exacerbations more frequently and demand much more home health care than patients with HF do. It seems that this difference of health care consumption is mainly due to disease characteristics.
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| 5. |
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| 6. |
- Lindberg, Owe
(författare)
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Talet om lärarutbildning
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this dissertation can be described as threefold, (i) to problematice the ways in which we talk about, or, the discourses of, teacher education, (ii) to analyse contemporary discussions about teacher education as it has taken shape in relation to the present teacher education reform in Sweden, and (iii) to develop points of references for alternative ways to talk about teacher education, on the basis of (i) and (ii), and in relation to Stephen Toulmin’s analysis of the modern project.The dissertation consists of twelve chapters divided into four parts. Part I is an introduction to the field of research and to the dissertation. Part II is an analysis of contemporary Swedish discussions about teacher education and teachers. Part III is an attempt to deepen the analysis by adding international and historical perspectives. Part IV, finally, takes the discussion another step further by using Toulmin’s analysis of the modern project as a lens through which to read the discourses about teacher education and teachers.Through a series of analyses the dissertation ends up in a discussion about how we could talk about teacher education within the spirit of the third modernity. The discussion is centred around five metaphors, “Teacher education as a public dialogue”, “Teacher education as the education of teachers”, “The education of teachers as an offer about Bildung in a citizenship perspective”, “The education of teachers as teachers education” and “Teachers education as communication”. In relation to these metaphors two lines of talk are suggested. We could start to talk about teachers work as if it was a profession with communicative and deliberative characteristics seen in the perspective of citizenship in terms of belonging and participation and we could start to talk about teachers education as if it was meant to create good conditions for becoming teachers to develop their capacity to make sound judgements in relation to their work by participating in critical, constructive and challenging dialogues.
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