| 1. |
- Nilsson, Johanna, 1993, et al.
(författare)
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Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease
- 2021
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed. Method Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37). Results Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased. Discussion We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.
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| 2. |
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| 3. |
- Afghahi, Henri, 1966, et al.
(författare)
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Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death.The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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| 4. |
- Afghahi, Henri, 1966, et al.
(författare)
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The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment.
- 2022
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75years.2487 patients (mean age 66years, 66% men) were separated in two age groups: ≤75years (n=1810) and>75years (n=677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models.1295 (52%) patients died and 473 (70%) among the patients above 75years old. In the multivariate analysis, HbA1c5-6% was used as reference. In patients≤75years old, only increased HbA1c>9.7%, HR2.03(CI1.43-2.89) was associated with increased risk of all-cause mortality. In patients>75years, HbA1c≤5%, HR1.67(CI1.16-2.40); HbA1c6.9-7.8%, HR1.41(CI1.03-1.93) and HbA1c8.7-9.7%, HR1.79 (CI1.08-2.96) were associated with increased risk of all-cause mortality.We found a J-shaped association between HbA1c and mortality only in diabetic HD-patients>75years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.
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| 5. |
- Axelsson, Elin, et al.
(författare)
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Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-β Protein Precursor β in the Subcortical Small Vessel Type of Dementia.
- 2023
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 96:4, s. 1515-1528
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Tidskriftsartikel (refereegranskat)abstract
- The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers.We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-β protein precursor α (sAβPPα), sAβPPβ, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD).This was a mono-center study of patients with SSVD (n=38), AD (n=121), mixed dementia (n=62), and controls (n=96). The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated.Elevated neurofilament light chain (NFL) and decreased sAβPPβ independently separated SSVD from controls, and sAβPPβ also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAβPPβ discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAβPPβ combined with the core AD biomarkers (amyloid-β42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830-0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838-0.968).The high accuracy of NFL and sAβPPβ to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAβPPβ in combination with the core AD biomarkers.
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| 6. |
- Axelsson, Elin, et al.
(författare)
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Patients with the Subcortical Small Vessel Type of Dementia Have Disturbed Cardiometabolic Risk Profile
- 2020
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 73:4, s. 1373-1383
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based studies have shown that cardiometabolic status is associated with the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). However, little is known of cardiometabolic risk factors in the subcortical small vessel type of dementia (SSVD), in which WMHs are one of the most prominent manifestations. Objective: To determine whether the profile of cardiometabolic risk factors differed between SSVD, Alzheimer's disease (AD), mixed dementia (combined AD and SSVD), and healthy controls. Methods: This was a mono-center, cross-sectional study of SSVD (n = 40), AD (n = 113), mixed dementia (n = 62), and healthy controls (n = 94). In the statistical analyses, we adjusted for covariates using ANCOVA and binary logistic regression. Results: The prevalence of hypertension was increased in SSVD and mixed dementia (p < 0.001 and p < 0.05 versus controls, respectively). Diabetes was more prevalent in SSVD patients, and body mass index was lower in AD and mixed dementia, compared to the controls (all p < 0.05). Serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) were reduced in the SSVD group (both p < 0.05 versus control). These differences remained after adjustment for covariates. In the SSVD group, Trail Making Test A score correlated positively with systolic blood pressure, mean arterial pressure, and pulse pressure. Conclusion: All dementia groups had an altered cardiometabolic risk profile compared to the controls. The SSVD patients showed increased prevalence of hypertension and diabetes, and in line with previous population-based data, TC and LDL-C in serum were reduced.
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| 7. |
- Deutschmann, Mats, 1964-, et al.
(författare)
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"It ain't what you say. It's the way you say it" : adapting the matched guise technique (MGT) to raise awareness of accentedness stereotyping effects among Swedish pre-service teachers
- 2023
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Ingår i: Language Awareness. - : Routledge. - 0965-8416 .- 1747-7565. ; 32:2, s. 255-277
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Tidskriftsartikel (refereegranskat)abstract
- The study describes a pedagogic adaptation of the matched guise technique with the aim to raise linguistic self-awareness of L2 accentedness stereotyping effects among Swedish pre-service teachers. In the experiment, 290 students attending teacher training programs were exposed to one of two matched guises, representing either L1 accented Swedish, or L2 accented Swedish. Both guises were based on the same recording, but the L2 accented version had been digitally manipulated using cut-and-paste techniques in order to replicate certain vowel sounds (the [u:]-sound in particular) associated with low-prestige Swedish L2 accentedness. The findings from this experiment were then used as starting point for language awareness raising activities. Our overall results show that the L2 accented manipulated recording was evaluated more favourably than the original L1 accented recording on all investigated variables. One proposed explanation is that respondents were inadvertently influenced by so-called shifting standards effects, i.e. lower standards/expectations are being used as reference points when evaluating the L2 accented recording. This tendency, however, seemed to be less apparent among respondents with bi/multilingual linguistic identities. Following debriefing discussions based on the experiment findings, there were clear indications that respondents did become more aware of inadvertent linguistic stereotyping by participating in the activities.
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| 8. |
- Eckerström, Carl, et al.
(författare)
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Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 73:2, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Research has shown that mixed dementia is more common than previously believed but little is known of its early stages.To examine if incipient mixed dementia can be differentiated from incipient Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SVD) using neuropsychological tests, cerebrospinal fluid (CSF) markers, and magnetic resonance imaging markers.We included 493 patients and controls from the Gothenburg MCI study and used the dementia groups for marker selection (CSF total-tau (T-tau), phospho-tau (P-tau), and amyloid-β42 (Aβ42), 11 neuropsychological tests, and 92 regional brain volumes) and to obtain cut-off values which were then applied to the MCI groups.Incipient mixed dementia was best differentiated from incipient AD by the Word fluency F-A-S test and the Trail making test A. CSF T-tau, P-tau, and Aβ42 differentiated incipient mixed dementia from incipient SVD.Incipient mixed dementia is characterized by an AD-like biomarker profile and an SVD-like cognitive profile. Incipient mixed dementia can be separated from incipient AD and incipient SVD using CSF markers and cognitive testing.
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| 9. |
- Eckerström, Carl, et al.
(författare)
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Evaluation of the ATN model in a longitudinal memory clinic sample with different underlying disorders.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the usefulness of the 2018 NIA-AA (National Institute on Aging and Alzheimer's Association) research framework in a longitudinal memory clinic study with different clinical outcomes and underlying disorders.We included 420 patients with mild cognitive impairment or subjective cognitive impairment. During the follow up, 27% of the patients converted to dementia, with the majority converting to Alzheimer's disease (AD) or mixed dementia. Based on the baseline values of the cerebrospinal fluid biomarkers, the patients were classified into one of the eight possible ATN groups (amyloid beta [Aβ] aggregation [A], tau aggregation reflecting neurofibrillary tangles [T], and neurodegeneration [N]).The majority of the patients converting to AD and mixed dementia were in ATN groups positive for A (71%). The A+T+N+ group was highly overrepresented among converters to AD and mixed dementia. Patients converting to dementias other than AD or mixed dementia were evenly distributed across the ATN groups.Our findings provide support for the usefulness of the ATN system to detect incipient AD or mixed dementia.
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| 10. |
- Fries, Johan, et al.
(författare)
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Key parameters for droplet evaporation and mixing at the cloud edge
- 2021
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Ingår i: Quarterly Journal of the Royal Meteorological Society. - : Wiley. - 0035-9009 .- 1477-870X. ; 147:737, s. 2160-2172
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of liquid water in ice-free clouds determines their radiative properties, a significant source of uncertainty in weather and climate models. Evaporation and turbulent mixing cause a cloud to display large variations in droplet number density, but quite small variations in droplet size (Beals et al., Science, 2015, vol. 350, pp. 87-90). However, direct numerical simulations of the joint effect of evaporation and mixing near the cloud edge predict quite different behaviours, and how to reconcile these results with the experimental findings remains an open question. To infer the history of mixing and evaporation from observational snapshots of droplets in clouds is challenging, because clouds are transient systems. We formulated a statistical model that provides a reliable description of the evaporation-mixing process as seen in direct numerical simulations and allows us to infer important aspects of the history of observed droplet populations, highlighting the key mechanisms at work and explaining the differences between observations and simulations.
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