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- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 4. |
- Flam, B., et al.
(författare)
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Direct oral anticoagulant use and risk of severe COVID-19
- 2021
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 289:3, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective.Methods: We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19.Results: DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). 'Conclusion: Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.
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| 6. |
- Pasternak, B., et al.
(författare)
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Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice. DESIGN Cohort study using an active comparator, new user design and nationwide register data. SETTING Sweden, Denmark, and Norway, 2013-18. PARTICIPANTS Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years. EXPOSURES SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat. MAIN OUTCOME MEASURES The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. RESULTS The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark. CONCLUSIONS In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.
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- Stephansson, O., et al.
(författare)
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SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study
- 2022
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Ingår i: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:2, s. 282-290
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. Design Nationwide cohort study. Setting Sweden. Population From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. Main outcome measures Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. Results During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive <= 10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). Conclusions Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. Tweetable abstract Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.
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| 10. |
- Ahmadi, Khazar, et al.
(författare)
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Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease
- 2024
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Ingår i: Journal of Neuroscience. - 0270-6474. ; 44:18
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.
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